Changes in the incidence, clinical features and outcomes of tuberculosis during COVID-19 pandemic.

BACKGROUND: COVID-19 pandemic has disrupted tuberculosis (TB) services in many countries, but the impacts on sites of involvement, drug susceptibility, smear positivity and clinical outcomes, and clinical outcomes of co-infection with influenza and COVID-19 remain unclear. METHODS: Descriptive epidemiological study using episode-based and patient unique data of tuberculosis from Hospital Authority's territory-wide electronic medical record database, comparing baseline (January 2015-December 2019) and COVID-19 period (January 2020-December 2022), followed by univariate and multivariate analyses. Effects of co-infection with influenza and COVID-19 were investigated. RESULTS: The study included 10,473 episodes of laboratory-confirmed TB, with 6818 in baseline period and 3655 during COVID-19 period. During COVID-19 period, TB patients had a lower proportion of smear positivity (49.2 % vs 54.7 %, P < 0.001), and fewer cases of extrapulmonary TB (7.0 % vs 8.0 %, P = 0.078) and multidrug resistant TB (1.0 % vs 1.6 %, P = 0.020). Mortality was higher in TB patients with COVID-19 coinfection (OR 1.7, P = 0.003) and influenza coinfection (OR 2.6, P = 0.004). During COVID-19 period, there were higher rates of treatment delay (20.5 % vs 15.5 %, P < 0.001) and episodic death (15.1 % vs 13.3 %, P = 0.006). Factors associated with higher mortality included age ≥ 70 years (OR 7.24), treatment delay (OR 2.16), extrapulmonary TB (OR 2.13). smear positivity (OR 1.71) and Charlson comorbidity index score ≥ 3 (OR 1.37). Higher mortality was observed with co-infection by influenza (OR 1.18) and COVID-19 (OR 1.7). CONCLUSIONS: The epidemiology and outcomes of TB were changed during COVID-19 period. Mortality was higher during COVID-19 period and with co-infection by influenza and COVID-19.

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

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.

Predictive Factors of Cloxacillin Susceptibility in Primary Bacterial Spinal Infection.

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 Staphylococcus isolates, 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.

Genomic investigation of Lactococcus formosensis, Lactococcus garvieae, and Lactococcus petauri reveals differences in species distribution by human and animal sources.

Lactococcus garvieae is a fish pathogen that can cause diseases in humans and cows. Two genetically related species, Lactococcus formosensis and Lactococcus petauri, may be misidentified as L. garvieae. It is unclear if these species differ in host specificity and virulence genes. This study analyzed the genomes of 120 L. petauri, 53 L. formosensis, and 39 L. garvieae isolates from various sources. The genetic diversity and virulence gene content of these isolates were compared. The results showed that 77 isolates previously reported as L. garvieae were actually L. formosensis or L. petauri. The distribution of the three species varied across different collection sources, with L. petauri being predominant in human infections, human fecal sources, and rainbow trout, while L. formosensis was more common in bovine isolates. The genetic diversity of isolates within each species was high and similar. Using a genomic clustering method, L. petauri, L. formosensis, and L. garvieae were divided into 45, 22, and 13 clusters, respectively. Most rainbow trout and human isolates of L. petauri belonged to different clusters, while L. formosensis isolates from bovine and human sources were also segregated into separate clusters. In L. garvieae, most human isolates were grouped into three clusters that also included isolates from food or other sources. Non-metric multidimensional scaling ordination revealed the differential association of 15 virulence genes, including 14 adherence genes and a bile salt hydrolase gene, with bacterial species and certain collection sources. In conclusion, this work provides evidence of host specificity among the three species. IMPORTANCE: Lactococcus formosensis and Lactococcus petauri are two newly discovered bacteria, which are closely related to Lactococcus garvieae, a pathogen that affects farmed rainbow trout, as well as causes cow mastitis and human infections. It is unclear whether the three bacteria differ in their host preference and the presence of genes that contribute to the development of disease. This study shows that L. formosensis and L. petauri were commonly misidentified as L. garvieae. The three bacteria showed different distribution patterns across various sources. L. petauri was predominantly found in human infections and rainbow trout, while L. formosensis was more commonly detected in cow mastitis. Fifteen genes displayed a differential distribution among the three bacteria from certain sources, indicating a genetic basis for the observed host preference. This work indicates the importance of differentiating the three bacteria in diagnostic laboratories for surveillance and outbreak investigation purposes.

Prevalence and Outcomes of Infections in Critically-ill Paediatric Oncology Patients: A Retrospective Observation Study.

PURPOSE: The survival of paediatric oncology patients has improved substantially in the past decades due to advances in the field of oncology. Modern cancer treatments often come with life-threatening complications, of which infection is one of the most common causes in this patient population. This study aims to investigate the prevalence and outcomes of common infections in haemato-oncology patients during their stay in paediatric intensive care unit (PICU) and to identify any factors associated with these infections. METHODS: A retrospective observational study was conducted on all children with a haemato-oncology diagnosis or who underwent haematopoietic stem cell transplantation (HSCT) and who were admitted to the Hong Kong Children's Hospital PICU over a one-year period. Infection characteristics and patient outcomes were evaluated and compared between different sub-groups. Univariable and multi-variable analyses were employed to identify risk factors associated with the development of active infection. RESULTS: Forty-five (36.3%) of 124 critically ill haemato-oncology admissions to PICU were associated with infections, of which 31 (25%) admissions involved bacterial infections, 26 (20.9%) involved viral infections and 6 (4.8%) involved fungal infections. Bloodstream infection was the most common type of infection. More than half (61.3%) of the bacterial infections were due to an antibiotic-resistant strain. After adjusting for confounding variables, post-HSCT status and neutropenia were significantly associated with active infections. CONCLUSION: Infections in critically-ill haemato-oncological patients are associated with post haematopoietic stem cell transplant status and neutropenia. Further study is warranted to review effective strategies that may mitigate the likelihood of infection in this patient population.

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

Introduction: 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 the two groups. Discussion: NMV-r was more effective than MOL among unvaccinated adults with chronic respiratory diseases who were hospitalized for moderate COVID-19 without hypoxaemia on admission.

Evaluation of Two Tests for the Rapid Detection of CTX-M Producers Directly in Urine Samples.

Infections caused by extended-spectrum ß-lactamase-producing Enterobacterales have increased rapidly and are mainly attributed to the production of CTX-M enzymes. This study evaluated the NG-Test® CTX-M MULTI lateral flow assay (CTX-M LFA) and the Rapid ESBL NP® test (ESBL NP test) for rapid detection of CTX-M-producing Enterobacterales directly in midstream urine (MSU) samples. Testing was performed on 277 clinical MSU samples in a hospital microbiology laboratory from November 2022 to January 2023; 60 of these samples (30 positive for ESBL producers and 30 positive for non-ESBL producers) were tested retrospectively after the identification and susceptibility results were obtained, and 217 samples were tested prospectively immediately after a Gram stain showing the presence of Gram-negative bacilli. The results were compared against phenotypic detection of ESBL and molecular testing as the reference methods. Overall, 67 of the 277 samples were culture-positive for ESBL-producing Enterobacterales. PCR for the blaCTX-M gene was positive for all ESBL-producing Enterobacterales isolates. All CTX-M LFA results were interpretable, while three of the ESBL NP test results were noninterpretable. The sensitivity of the CTX-M LFA (100%, 95% CI 94.6-100%) was higher than that of the ESBL NP test (86.6%, 95% CI 76.0-93.7%). Both tests had high specificities (CTX-M LFA, 99.1%, 95% CI 96.6-99.9% and ESBL NP test, 100%, 95% CI 98.2-100%). In conclusion, both the CTX-M LFA and the ESBL NP test can deliver rapid results that could improve antimicrobial stewardship for urinary tract infections.

Metallo-sideromycin as a dual functional complex for combating antimicrobial resistance.

The rapid emergence of antimicrobial resistance (AMR) pathogens highlights the urgent need to approach this global burden with alternative strategies. Cefiderocol (Fetroja®) is a clinically-used sideromycin, that is utilized for the treatment of severe drug-resistant infections, caused by Gram-negative bacteria; there is evidence of cefiderocol-resistance occurring in bacterial strains however. To increase the efficacy and extend the life-span of sideromycins, we demonstrate strong synergisms between cefiderocol and metallodrugs (e.g., colloidal bismuth citrate (CBS)), against Pseudomonas aeruginosa and Burkholderia cepacia. Moreover, CBS enhances cefiderocol efficacy against biofilm formation, suppresses the resistance development in P. aeruginosa and resensitizes clinically isolated resistant P. aeruginosa to cefiderocol. Notably, the co-therapy of CBS and cefiderocol significantly increases the survival rate of mice and decreases bacterial loads in the lung in a murine acute pneumonia model. The observed phenomena are partially attributable to the competitive binding of Bi3+ to cefiderocol with Fe3+, leading to enhanced uptake of Bi3+ and reduced levels of Fe3+ in cells. Our studies provide insight into the antimicrobial potential of metallo-sideromycins.

Antimicrobial susceptibility of Bacteroides fragilis group organisms in Hong Kong, 2020-2021.

OBJECTIVES: This retrospective study analyzed the susceptibility levels of Bacteroides fragilis group (BFG) in a hospital-based laboratory where disk diffusion test (DDT) was routinely performed. Isolates non-susceptible to imipenem and metronidazole by DDT were further investigated using a gradient method. METHODS: The DDT and MIC susceptibility data of clindamycin, metronidazole, moxifloxacin and imipenem obtained on Brucella blood agar for 1264 non-duplicated isolates during 2020-2021 were analyzed. Species identification was obtained by matrix-assisted laser desorption ionization time-of-flight mass spectrometry and 16S rRNA sequencing. Interpretative agreement of DDT results using the 2015 EUCAST tentative and 2021 CA-SFM breakpoints was compared against MIC as the reference. RESULTS: The dataset included 604 B. fragilis (483 division I, 121 division II isolates), 415 non-fragilis Bacteroides, 177 Phocaeicola and 68 Parabacteroides. Susceptibility rates for clindamycin (22.1-62.1%) and moxifloxacin (59.9-80.9%) were low and many had no inhibition zones. At the EUCAST and CA-SFM breakpoints, 83.0 and 89.4% were imipenem-susceptible, and 89.6% and 97.4 were metronidazole-susceptible. MIC testing confirmed 11.4% and 2.8% isolates as imipenem-non-susceptible and metronidazole-resistant, respectively. Significant numbers of false-susceptibility and/or false-resistance results were observed at the CA-SFM breakpoint but not the EUCAST breakpoint. Higher rates of imipenem and/or metronidazole resistance were detected in B. fragilis division II, B. caccae, B. ovatus, B. salyersiae, B. stercoris and Parabacteroides. Co-resistance to imipenem and metronidazole was detected in 3 B. fragilis division II isolates. CONCLUSIONS: The data demonstrated emerging BFG resistance to several important anti-anaerobic antibiotics and highlights the importance of anaerobic susceptibility testing in clinical laboratories to guide therapy.

Epidemiology of multidrug-resistant organisms before and during COVID-19 in Hong Kong.

Background: The coronavirus disease 2019 (COVID-19) has influenced antimicrobial consumption and incidence of multidrug-resistant organisms (MDROs). We aimed to study the epidemiology of MDROs before and during the COVID-19 pandemic in Hong Kong. Methods: With the maintenance of infection control measures, we described the trend of MDRO infections, including methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Acinetobacter species (CRA), and extended-spectrum-beta-lactamase-(ESBL)-producing Enterobacterales, in a healthcare region with 3100-bed before (1 January 2016 to 31 December 2019, period 1) and during COVID-19 (1 January 2020 to 30 September 2022, period 2), together with the antimicrobial consumption using piecewise Poisson regression. The epidemiological characteristics of newly diagnosed COVID-19 patients with or without MDRO infections were analyzed. Results: Between period 1 and 2, we observed a significant increase in the trend of CRA infections (P<0.001), while there was no significant increase in the trend of MRSA (P=0.742) and ESBL-producing Enterobacterales (P=0.061) infections. Meanwhile, a significant increase in the trend of carbapenems (P<0.001), extended-spectrum beta-lactam-beta-lactamase inhibitor combinations (BLBI) (P=0.045), and fluoroquinolones (P=0.009) consumption was observed. The observed opportunity (23,540 ± 3703 vs 26,145 ± 2838, p=0.359) and compliance (81.6% ± 0.5% vs 80.1% ± 0.8%, P=0.209) of hand hygiene per year was maintained. In a multivariable model, older age, male sex, referral from residential care home for the elderly, presence of indwelling device, presence of endotracheal tube, and use of carbapenems, use of BLBI, use of proton pump inhibitors and history of hospitalization in the past 3 months were associated with higher risks of infections by MDROs among COVID-19 patients. Conclusion: Infection control measures may control the surge of MDROs despite an increasing trend of antimicrobial consumption.

Genomic Investigation of Salmonella Typhi in Hong Kong Revealing the Predominance of Genotype 3.2.2 and the First Case of an Extensively Drug-Resistant H58 Genotype.

Typhoid fever is a notable disease in Hong Kong. We noticed two local cases of typhoid fever caused by Salmonella Typhi within a two-week period in late 2022, which had no apparent epidemiological linkage except for residing in the same region of Hong Kong. A phylogenetic study of Salmonella Typhi isolates from Hong Kong Island from 2020 to 2022 was performed, including a whole-genome analysis, the typing of plasmids, and the analysis of antibiotic-resistance genes (ARGs), to identify the dominant circulating strain and the spread of ARGs. A total of seven isolates, from six local cases and an imported case, were identified from positive blood cultures in two hospitals in Hong Kong. Five antibiotic-sensitive strains of genotype 3.2.2 were found, which clustered with another 30 strains originating from Southeast Asia. Whole-genome sequencing revealed clonal transmission between the two index cases. The remaining two local cases belong to genotype 2.3.4 and genotype 4.3.1.1.P1 (also known as the H58 lineage). The genotype 4.3.1.1.P1 strain has an extensively drug-resistant (XDR) phenotype (co-resistance to ampicillin, chloramphenicol, ceftriaxone, ciprofloxacin, and co-trimoxazole). Although the majority of local strains belong to the non-H58 genotype 3.2.2 with a low degree of antibiotic resistance, the introduction of XDR strains with the global dissemination of the H58 lineage remains a concern.

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.

While molnupiravir (MOV) and nirmatrelvir-ritonavir (NMV-r) were developed for treatment of mild to moderate COVID-19 infection, there has been a lack of data on the efficacy among unvaccinated adult patients with chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD) and bronchiectasis. A territory-wide retrospective cohort study was conducted in Hong Kong to investigate the efficacy of MOV and NMV-r against severe outcomes of COVID-19 in unvaccinated adult patients with chronic respiratory diseases. A total of 3267 patients were included. NMV-r was effective in preventing respiratory failure (66.6%; 95% CI, 25.6-85.0%, p = 0.007), severe respiratory failure (77.0%; 95% CI, 6.9-94.3%, p = 0.039) with statistical significance, and COVID-19 related hospitalization (43.9%; 95% CI, -1.7-69.0%, p = 0.057) and in-hospital mortality (62.7%; 95% CI, -0.6-86.2, p = 0.051) with borderline statistical significance. MOV was effective in preventing COVID-19 related severe respiratory failure (48.2%; 95% CI 0.5-73.0, p = 0.048) and in-hospital mortality (58.3%; 95% CI 22.9-77.4, p = 0.005) but not hospitalization (p = 0.16) and respiratory failure (p = 0.10). In summary, both NMV-r and MOV are effective for reducing severe outcomes in unvaccinated COVID-19 patients with chronic respiratory diseases.

Changes in Etiology and Clinical Outcomes of Pleural empyema during the COVID-19 Pandemic.

Healthcare-seeking behavior changed during the COVID-19 pandemic and might alter the epidemiology of pleural empyema. In this study, the incidence, etiology and outcomes of patients admitted for pleural empyema in Hong Kong in the pre-COVID-19 (January 2015-December 2019) and post-COVID-19 (January 2020-June 2022) periods were compared. Overall, Streptococcus pneumoniae was the predominant organism in <18-year-old patients, while Streptococcus anginosus, anaerobes and polymicrobial infections were more frequent in adults. In the post-COVID-19 period, a marked decline in the incidence of pleural empyema in children was observed (pre-COVID-19, 18.4 ± 4.8 vs. post-COVID-19, 2.0 ± 2.9 cases per year, p = 0.036), while the incidence in adults remained similar (pre-COVID-19, 189.0 ± 17.2 vs. post-COVID-19, 198.4 ± 5.0 cases per year; p = 0.23). In the post-COVID-19 period, polymicrobial etiology increased (OR 11.37, p < 0.0001), while S. pneumoniae etiology decreased (OR 0.073, p < 0.001). In multivariate analysis, clinical outcomes (length of stay, ICU admission, use of intrapleural fibrinolytic therapy, surgical intervention, death) were not significantly different in pre- and post-COVID-19 periods. In conclusion, an increase in polymicrobial pleural empyema was observed during the pandemic. We postulate that this is related to the delayed presentation of pneumonia to hospitals.

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

Background: 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 vaccination, with adjusted odds ratio (OR) of 0.189 (95% CI = 0.050-0.714, p = 0.014) and 0.128 (95% CI = 0.026-0.638, p = 0.012) respectively. Patients who received at least 2 doses of BNT162b2 had lower risk of being hospitalized for COVID-19 and developing respiratory failure than those who did not have vaccination with adjusted OR of 0.207 (95% CI = 0.043-0.962, p = 0.050) and 0.093 (95% CI = 0.011-0.827, p = 0.033) respectively. There was no statistically significant difference in the risks of being hospitalized for COVID-19 and developing respiratory failure between patients who received at least 2 doses of CoronaVac or BNT162b2. Conclusion: BNT162b2 and CoronaVac vaccines are effective in preventing hospitalization for COVID-19 and respiratory failure complicating COVID-19 among patients with chronic respiratory diseases. Patients with chronic respiratory diseases should be encouraged to have COVID-19 vaccination.

Evaluation of a Lateral Flow Immunoassay for Rapid Detection of CTX-M Producers from Blood Cultures.

Bacteremia caused by extended-spectrum ß-lactamases-producing Enterobacterales has increased rapidly and is mainly attributed to CTX-M enzymes. This study aimed to evaluate the NG-Test® CTX-M MULTI lateral flow assay (CTX-M LFA) for rapid detection of CTX-M producers in blood cultures (BCs) positive for Gram-negative bacilli in spiked and clinical BCs. Retrospective testing was performed on BC bottles spiked with a collection of well-characterized Enterobacterales isolates producing CTX-M (n = 15) and CTX-M-like (n = 27) ß-lactamases. Prospective testing of clinical, non-duplicate BCs (n = 350) was performed in two hospital microbiology laboratories from April 2021 to March 2022 following detection of Gram-negative bacilli by microscopic examination. Results were compared against molecular testing as the reference. In the spiked BCs, the CTX-M LFA correctly detected all CTX-M producers including 5 isolates with hybrid CTX-M variants. However, false-positive results were observed for several CTX-M-like ß-lactamases, including OXY-1-3, OXY-2-8, OXY-5-3, FONA-8, -9, -10, 11, 13 and SFO-1. In clinical BCs, the CTX-M LFA showed 100% (95% CI, 96.0-100%) sensitivity and 99.6% (97.9-100%) specificity. In conclusion, this study showed that rapid detection of CTX-M producers in BC broths can be reliably achieved using the CTX-M LFA, thus providing an opportunity for early optimization of antibiotics.

Gold drugs as colistin adjuvants in the fight against MCR-1 producing bacteria.

The emergence and rapid spread of the mobile colistin resistance gene mcr-1 among bacterial species and hosts significantly challenge the efficacy of "last-line" antibiotic colistin. Previously, we reported silver nitrate and auranofin serve as colistin adjuvants for combating mcr-1-positive bacteria. Herein, we uncovered more gold-based drugs and nanoparticles, and found that they exhibited varying degree of synergisms with colistin on killing mcr-1-positive bacteria. However, pre-activation of the drugs by either glutathione or N-acetyl cysteine, thus releasing and accumulating gold ions, is perquisite for their abilities to substitute zinc cofactor from MCR-1 enzyme. X-ray crystallography and biophysical studies further supported the proposed mechanism. This study not only provides basis for combining gold-based drugs and colistin for combating mcr-1-positive bacterial infections, but also undoubtedly opens a new horizon for metabolism details of gold-based drugs in overcoming antimicrobial resistance.

Comparative analysis of outer membrane vesicles from uropathogenic Escherichia coli reveal the role of aromatic amino acids synthesis proteins in motility.

Uropathogenic Escherichia coli (UPEC) are causative agent that causes urinary tract infections (UTIs) and the recent emergence of multidrug resistance (MDR) of UPEC increases the burden on the community. Recent studies of bacterial outer membrane vesicles (OMV) identified various factors including proteins, nucleic acids, and small molecules which provided inter-cellular communication within the bacterial population. However, the components of UPEC-specific OMVs and their functional role remain unclear. Here, we systematically determined the proteomes of UPEC-OMVs and identified the specific components that provide functions to the recipient bacteria. Based on the functional network of OMVs' proteomes, a group of signaling peptides was found in all OMVs which provide communication among bacteria. Moreover, we demonstrated that treatment with UPEC-OMVs affected the motility and biofilm formation of the recipient bacteria, and further identified aromatic amino acid (AAA) biosynthesis proteins as the key factors to provide their movement.

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

Hong Kong SAR has adopted universal masking, social distancing, testing of all symptomatic and high-risk groups for isolation of confirmed cases in healthcare facilities, and quarantine of contacts as epidemiological control measures without city lockdown or border closure. These measures successfully suppressed the community transmission of pre-Omicron SARS-CoV-2 variants or lineages during the first to the fourth wave. No nosocomial SARS-CoV-2 infection was documented among healthcare workers in the first 300 days. The strategy of COVID-19 containment was adopted to provide additional time to achieve population immunity by vaccination. The near-zero COVID-19 situation for about 8 months in 2021 did not enable adequate immunization of the eligible population. A combination of factors was identified, especially population complacency associated with the low local COVID-19 activity, together with vaccine hesitancy. The importation of the highly transmissible Omicron variant kickstarted the fifth wave of COVID-19, which could no longer be controlled by our initial measures. The explosive fifth wave, which was partially contributed by vertical airborne transmission in high-rise residential buildings, resulted in over one million cases of infection. In this review, we summarize the epidemiology of COVID-19 and the infection control and public health measures against the importation and dissemination of SARS-CoV-2 until day 1000.

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

The epidemiology of patients with gastrointestinal colonization of carbapenem-resistant Acinetobacter baumannii (CRAB) has not been systematically analyzed. We aimed to analyze the incidence, risk factors, and clinical outcomes of patients with newly identified gastrointestinal colonization of CRAB in a healthcare region in Hong Kong, where a multi-pronged screening strategy for gastrointestinal colonization of CRAB, together with other multidrug-resistant organisms (MDROs), was conducted by collecting fecal specimens (rectal swab or stool) upon admission and during hospitalization. From 1 October 2015 to 31 December 2019, a total of 161,339 fecal specimens from 63,588 patients, 61,856 (97.3%) of whom were hospitalized patients, and 54,525 (88.1%) were screened upon admission, with 1309 positive for CRAB (2.4% prevalence). Among patients positive for CRAB in fecal specimens, 698 (53.3%) had newly detected gastrointestinal colonization of CRAB, giving an incidence of 10.03 per 10,000 patient admissions and constituting 2646 CRAB colonization days in the general wards. Excluding the 164 patients with co-colonization of other MDROs, 534 patients had gastrointestinal colonization with only CRAB, and 12.5% (67/534) developed symptomatic CRAB infections at a median of 61 days (range: 2 to 671 days), during prospective follow-up for 2 years. Compared with age- and sex-matched controls, patients being referred from residential care homes for the elderly, the presence of indwelling devices, use of beta-lactam/beta-lactamase inhibitors, carbapenems, and proton pump inhibitors in the preceding 6 months, and history of hospitalization in the past 6 months were significantly associated with gastrointestinal colonization with CRAB, as shown by multivariable analysis. Log-rank test showed that cases had significantly shorter survival duration than controls (p < 0.001). The adjusted hazard ratio of gastrointestinal colonization of CRAB was 1.8 (95% CI: 1.5−2.2; p < 0.001), as shown by Cox regression analysis. Whole-genome sequencing of eight patients with CRAB isolates in their blood cultures and rectal swabs during the same episode of hospitalization revealed ST-195 as the predominant type, as shown by multilocus sequencing type. Gastrointestinal colonization of CRAB poses a considerable challenge for infection prevention and control.