Impact of antibiotic stewardship programmes in Asia: a systematic review and meta-analysis.

Background: The use of antibiotic stewardship programmes (ASPs) is increasing in Asia, but their effectiveness in reducing antibiotic consumption and their impact on clinical outcomes is not known. Objectives: To determine the impact of ASPs conducted in Asia on the consumption of antibiotics and on patients' clinical outcomes. Methods: We systematically searched the Embase and Medline (PubMed) databases for studies that compared antibiotic consumption or clinical outcomes of patients in an Asian hospital or clinic with an ASP (intervention) with those in a similar setting without an ASP (control). Meta-analyses of all-cause mortality and hospital-acquired infection (HAI) were performed using random-effects models. Results: The search identified 77 studies of which 22 and 19 reported antibiotic usage and cost, respectively. Among these, 20 (91%) studies reported reduced antibiotic usage and 19 (100%) reported cost savings in the intervention group. Duration of antibiotic therapy was reduced in six of seven studies in association with an ASP. Rates of all-cause mortality and HAI were not significantly different between the intervention and control groups. However, mortality rates were significantly improved by ASPs using drug monitoring, while HAI rates were also improved by ASPs that included infection control or hand hygiene programmes. Conclusions: In Asia, ASPs reduce antibiotic consumption in hospital and clinic settings and do not worsen clinical outcomes. The findings strongly support the broad implementation of antimicrobial stewardship interventions in hospital and clinic settings in Asia.

Ten years of hand hygiene excellence: a summary of outcomes, and a comparison of indicators, from award-winning hospitals worldwide.

BACKGROUND: Hand hygiene is a crucial measure for the prevention of healthcare-associated infections (HAIs). The Hand Hygiene Excellence Award (HHEA) is an international programme acknowledging healthcare facilities for their leadership in implementing hand hygiene improvement programmes, including the World Health Organisation's Multimodal Improvement Strategy. This study aimed at summarising the results of the HHEA campaign between 2010 and 2021 and investigating the relationship between different hand hygiene parameters based on data from participating healthcare facilities. METHODS: A retrospective analysis was performed on datasets from HHEA forms, including data on hand hygiene compliance, alcohol-based handrub (ABHR) consumption, and Hand Hygiene Self-Assessment Framework (HHSAF) scores. Descriptive statistics were reported for each variable. The correlation between variables was inspected through Kendall's test, while possible non-linear relationships between hand hygiene compliance, ABHR consumption and HHSAF scores were sought through the Locally Estimated Scatterplot Smoothing or logistic regression models. A tree-structured partitioning model was developed to further confirm the obtained findings. RESULTS: Ninety-seven healthcare facilities from 28 countries in three world regions (Asia-Pacific, Europe, Latin America) were awarded the HHEA and thus included in the analysis. HHSAF scores indicated an advanced hand hygiene promotion level (median 445 points, IQR 395-480). System change (100 [95-100] points) and institutional safety climate (85 [70-95] points) showed the highest and lowest score, respectively. In most cases, hand hygiene compliance was above 70%, with heterogeneity between countries. ABHR consumption above 20 millilitres per patient-day (ml/PD) was widely reported, with overall increasing trends. HHSAF scores were positively correlated with hand hygiene compliance (τ = 0.211, p = 0.007). We observed a positive correlation between compliance rates and ABHR consumption (τ = 0.193, p < 0.001), although the average predicted consumption was stable around 55-60 ml/PD for compliance rates above 80-85%. Logistic regression and partitioning tree analyses revealed that higher HHSAF scores were more likely in the high-ABHR consumption group at cut-offs around 57-59 ml/PD. CONCLUSION: Ten years after its inception, the HHEA proves to be a valuable hand hygiene improvement programme in healthcare facilities worldwide. Consistent results were provided by the different hand hygiene indicators and the HHSAF score represents a valuable proxy measure of hand hygiene compliance.

Years of life lost in the first wave of the 2009 influenza A(H1N1) pandemic in Hong Kong.

The impact of influenza pandemics might be overestimated; the published studies of years of life lost (YLL) have typically ignored the presence of underlying chronic conditions or health risk behaviors in most deaths. We used data on deaths involving laboratory-confirmed 2009 influenza A(H1N1) virus infection that occurred between April 2009 and May 2010 in Hong Kong, China, to adjust for these underlying risk factors. Life expectancy was corrected with hazard-based modifications to the life tables. The excess hazards posed by underlying risk factors were added to the "baseline" age-specific hazards in the local life tables to reflect the life expectancy associated with each underlying risk factor. Of 72 deceased persons with laboratory-confirmed 2009 influenza A(H1N1) virus infection, 56% had underlying risk factors. We estimated that the 2009 pandemic was associated with 1,540 (95% confidence interval: 1,350, 1,630) YLL after adjustment for age and underlying risk factors. This figure is approximately 25% lower than the YLL estimate of 2,080 derived after adjustment for age but not for risk factors. Our analysis demonstrates the potential scale of bias in YLL estimation if underlying risk factors are ignored. The estimation of YLL with correction for underlying risk factors in addition to age could also provide a framework for similar calculations elsewhere.

Carbapenem resistance among Gram-negative isolates collected from patients in ICU and non-ICU hospital wards in Hong Kong: SMART 2017-2020.

OBJECTIVES: The aim of this study was to estimate carbapenem resistance in Pseudomonas aeruginosa and Enterobacterales isolated from infected patients in intensive care unit (ICU) and non-ICU hospital wards in Hong Kong. METHODS: Isolates of Pseudomonas aeruginosa (ICU, n = 35; non-ICU, n = 264) and Enterobacterales (ICU, n = 129; non-ICU, n = 1390) were collected in four Hong Kong hospitals in 2017-2020. Clinical and Laboratory Standards Institute broth microdilution minimum inhibitory concentrations (MICs) were interpreted according to Clinical and Laboratory Standards Institute 2021 M100 breakpoints. ß-lactamase genes were identified in imipenem-, imipenem/relebactam-, and ceftolozane/tazobactam-nonsusceptible isolates. RESULTS: Ceftolozane/tazobactam demonstrated potent in vitro activity against both P. aeruginosa (ICU, 88.6%; non-ICU, 98.5%) and Enterobacterales (96.1%; 97.1%). Percent susceptible values for P. aeruginosa isolates from ICU and non-ICU patients, respectively, were as follows: meropenem (ICU, 74.3%; non-ICU, 84.1%) and imipenem (68.6%; 73.1%). Only 1 of 77 isolates tested for ß-lactamase genes carried a carbapenemase (VIM-2). Percent susceptible values for Enterobacterales isolates from ICU and non-ICU patients were as follows: meropenem (100%; 99.4%), ertapenem (100%; 98.0%), and imipenem (88.4%; 88.6%). A total of 62 Enterobacterales isolates were tested for ß-lactamase genes. Only three isolates carried a carbapenemase gene; two (both Escherichia coli) were metallo-ß-lactamase-positive (both NDM-5), and one (Klebsiella pneumoniae) was OXA-48-like-positive. CONCLUSIONS: Carbapenem-nonsusceptible isolates of P. aeruginosa were common (>15% of isolates). P. aeruginosa percent susceptible values for ceftolozane/tazobactam (97.3% susceptible overall) were ≥14% higher than those for carbapenems in both ICU and non-ICU isolates. Carbapenemases were rare among both P. aeruginosa (one isolate) and Enterobacterales (three isolates). Most Enterobacterales isolates tested from ICU and non-ICU patients in Hong Kong hospitals in 2017-2020 were susceptible to meropenem and ertapenem (≥98%); imipenem was less active (89% susceptible).

Activity of ceftolozane/tazobactam against Gram-negative isolates among different infections in Hong Kong: SMART 2017-2019.

Introduction. Ceftolozane/tazobactam was approved by the Drug Office, Department of Health, Government of the Hong Kong Special Administrative Region in 2017.Hypothesis/Gap Statement. Currently the in vitro activity of ceftolozane/tazobactam against Gram-negative pathogens isolated from patients in Hong Kong is undocumented. It would be prudent to document the activity of ceftolozane/tazobactam against Pseudomonas aeruginosa and Enterobacterales isolated from hospitalized patients in Hong Kong.Aim. To describe the in vitro susceptibility of recent clinical isolates of P. aeruginosa and the two most common Enterobacterales species (Klebsiella pneumoniae, Escherichia coli) cultured from respiratory tract, intra-abdominal, urinary tract and bloodstream infection samples to ceftolozane/tazobactam and other commonly used antimicrobial agents.Methodology. CLSI-defined broth microdilution MICs were determined and interpreted for Gram-negative isolates collected in Hong Kong from 2017 to 2019 by the SMART surveillance programme.Results. For P. aeruginosa, 96.7 % of isolates (n=210) were susceptible to ceftolozane/tazobactam, while susceptibility rates were ≥14 % lower to meropenem (82.9 % susceptible), cefepime (82.4 %), ceftazidime (81.4 %), piperacillin/tazobactam (76.7 %) and levofloxacin (79.5 %). Ceftolozane/tazobactam inhibited 85.7 % of piperacillin/tazobactam-nonsusceptible isolates, 80.6-82.1 % of cefepime-, ceftazidime- or meropenem-nonsusceptible isolates, and 75.9 % of multidrug-resistant (MDR) isolates of P. aeruginosa. For K. pneumoniae, 96.1 % of isolates (n=308) were susceptible to ceftolozane/tazobactam compared with meropenem (99.0 % susceptible), piperacillin/tazobactam (93.8 %), cefepime (85.7 %) and ceftazidime (85.4 %). The majority (88.3 %) of ESBL (extended-spectrum ß-lactamase) non-CRE (carbapenem-resistant Enterobacterales) phenotype isolates of K. pneumoniae were susceptible to ceftolozane/tazobactam, comparable to piperacillin/tazobactam (85.0 %) but lower than meropenem (100 %). For E. coli, 98.5 % of isolates (n=609) were susceptible to ceftolozane/tazobactam compared to meropenem (99.3 % susceptible), piperacillin/tazobactam (96.7 %), ceftazidime (82.3 %) and cefepime (76.5 %). The majority (96.7 %) of ESBL non-CRE phenotype isolates of E. coli were susceptible to ceftolozane/tazobactam, similar to both meropenem (100 %) and piperacillin/tazobactam (94.5 %).Conclusions. Overall, >96 % of clinical isolates of P. aeruginosa, K. pneumoniae and E. coli collected in Hong Kong in 2017-2019 were susceptible to ceftolozane/tazobactam, while the activity of several commonly prescribed ß-lactams was reduced, especially for P. aeruginosa. Continued surveillance of ceftolozane/tazobactam and other agents is warranted.

Clinical and nonclinical health care workers faced a similar risk of acquiring 2009 pandemic H1N1 infection.

Reporting of confirmed pandemic influenza A virus (pH1N1) 2009 infection was mandatory among health care workers in Hong Kong. Among 1158 confirmed infections, there was no significant difference in incidence among clinical versus nonclinical staff (relative risk, 0.98; 95% confidence interval, 0.78-1.20). Reported community exposure to pH1N1 was common and was similar in both groups.

Facemasks and hand hygiene to prevent influenza transmission in households: a cluster randomized trial.

BACKGROUND: Few data are available about the effectiveness of nonpharmaceutical interventions for preventing influenza virus transmission. OBJECTIVE: To investigate whether hand hygiene and use of facemasks prevents household transmission of influenza. DESIGN: Cluster randomized, controlled trial. Randomization was computer generated; allocation was concealed from treating physicians and clinics and implemented by study nurses at the time of the initial household visit. Participants and personnel administering the interventions were not blinded to group assignment. (ClinicalTrials.gov registration number: NCT00425893) SETTING: Households in Hong Kong. PATIENTS: 407 people presenting to outpatient clinics with influenza-like illness who were positive for influenza A or B virus by rapid testing (index patients) and 794 household members (contacts) in 259 households. INTERVENTION: Lifestyle education (control) (134 households), hand hygiene (136 households), or surgical facemasks plus hand hygiene (137 households) for all household members. MEASUREMENTS: Influenza virus infection in contacts, as confirmed by reverse-transcription polymerase chain reaction (RT-PCR) or diagnosed clinically after 7 days. RESULTS: Sixty (8%) contacts in the 259 households had RT-PCR-confirmed influenza virus infection in the 7 days after intervention. Hand hygiene with or without facemasks seemed to reduce influenza transmission, but the differences compared with the control group were not significant. In 154 households in which interventions were implemented within 36 hours of symptom onset in the index patient, transmission of RT-PCR-confirmed infection seemed reduced, an effect attributable to fewer infections among participants using facemasks plus hand hygiene (adjusted odds ratio, 0.33 [95% CI, 0.13 to 0.87]). Adherence to interventions varied. LIMITATION: The delay from index patient symptom onset to intervention and variable adherence may have mitigated intervention effectiveness. CONCLUSION: Hand hygiene and facemasks seemed to prevent household transmission of influenza virus when implemented within 36 hours of index patient symptom onset. These findings suggest that nonpharmaceutical interventions are important for mitigation of pandemic and interpandemic influenza. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

Author Correction: Respiratory virus shedding in exhaled breath and efficacy of face masks.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Respiratory virus shedding in exhaled breath and efficacy of face masks.

We identified seasonal human coronaviruses, influenza viruses and rhinoviruses in exhaled breath and coughs of children and adults with acute respiratory illness. Surgical face masks significantly reduced detection of influenza virus RNA in respiratory droplets and coronavirus RNA in aerosols, with a trend toward reduced detection of coronavirus RNA in respiratory droplets. Our results indicate that surgical face masks could prevent transmission of human coronaviruses and influenza viruses from symptomatic individuals.

Determinants of methicillin-resistant Staphylococcus aureus (MRSA) prevalence in the Asia-Pacific region: A systematic review and meta-analysis.

OBJECTIVES: Published literature on methicillin-resistant Staphylococcus aureus (MRSA) in the Asia-Pacific region was reviewed to document the prevalence of MRSA in the region and to examine the impact of variability in study design on the reported MRSA prevalence data. METHODS: This review included studies reporting MRSA prevalence between 2000 and 2016. Studies were excluded if they did not contain complete information on antimicrobial susceptibility testing (AST) methods. Primary outcomes were the proportion of MRSA among S. aureus isolates (resistance proportion) or among individual samples (prevalence). RESULTS: A total of 229 studies in 19 countries/territories were included in the study. There was substantial heterogeneity in both outcomes (resistance proportion, I2=99.59%; prevalence, I2=99.83%), precluding pooled averages, and meta-regression analyses revealed that these variations were explained by country income status and participant characteristics but not by methodological differences in AST. Also, no significant secular changes in MRSA prevalence or resistance proportions in Asia-Pacific were found. CONCLUSION: The resistance proportions and prevalence of MRSA infections in Asia-Pacific are comparable with those reported in other regions with no significant secular changes in the past decade. Country income status and characteristics of the sample population explained more variation in the reported resistance proportions and prevalence of MRSA than methodological differences in AST across locations in the region.

Epidemiology and genetic diversity of methicillin-resistant Staphylococcus aureus strains in residential care homes for elderly persons in Hong Kong.

OBJECTIVE: To determine the prevalence and molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) strains among residents in residential care homes for the elderly in Hong Kong. DESIGN: Cross-sectional and descriptive study. PARTICIPANTS: A total of 949 residents in 13 residential care homes for elderly persons in Hong Kong in January 2005. METHODS: MRSA colonization was assessed by culture of swab specimens from anterior nares and active skin lesions. Characteristics of residents were obtained by a standard questionnaire. All MRSA isolates were analyzed by polymerase chain reaction for their staphylococcal cassette chromosome (SCC) mec content and were typed by pulsed-field gel electrophoresis (PFGE) and multilocus sequencing. RESULTS: MRSA colonization was detected in 27 residents (2.8%). No MRSA was found in 2 facilities. The rate of MRSA carriage in the other 11 facilities ranged from 1.9% to 4.2%. In univariate analysis, functional immobility (odds ratio [OR], 1.4), history of hospital admission (OR, 2.3), and the use of nebulized medication (OR, 5.4) were significantly associated with MRSA colonization. The isolates had 11 unique antibiograms, with 14 isolates susceptible to all but 1 or 2 of the non- beta -lactam antimicrobial agents tested. The isolates exhibited SCCmec types I (1 isolate), II (2 isolates), III (1 isolate), IV/IVA (10 isolates), and V (13 isolates). No isolates had the Panton-Valentine leukocidin genes. PFGE analysis clustered all except 1 isolate into 7 PFGE types, designated HKU10 to HKU70. Between 1 and 4 unique PFGE types were found in the individual residential care facilities. CONCLUSION: This study documented the emergence of SCCmec types IV and V among genetically diverse MRSA strains in residential care homes for elderly persons in Hong Kong.

Diagnostic application of genotypic identification of mycobacteria.

This study evaluated conventional methods, GLC and three molecular tests, including 16S rRNA sequencing, for the identification of mycobacteria, and the experiences of the authors with the integration of these methods into a diagnostic clinical laboratory were also recorded. Of 1067 clinical isolates of mycobacteria identified by conventional tests, 365 were tested by Accuprobe hybridization assays and PCRs specific for Mycobacterium tuberculosis (MTB) complex or Mycobacterium avium complex (MAC), 202 were tested by 16S rRNA sequencing, and 142 were tested by GLC. Three runs of all tests were performed on a weekly basis. The identifications for 209 MTB complex and 118 MAC isolates obtained by species-specific PCR were in complete agreement with AccuProbe hybridization and conventional test results. The 16S rRNA sequence-based identification, at a similarity of > or =99 %, for 132 of 142 isolates was concordant with the identifications made by the biochemical methods, and for 134 isolates was concordant with the identifications made by GLC at species, group or complex level. 16S rRNA sequencing resulted in fewer incorrectly identified or unidentified organisms than GLC or conventional tests. For the slowly growing non-tuberculous mycobacteria, the mean turnaround times for identification were 4-5 days for 16S rRNA sequencing, 14-29 days for GLC and 22-23 days for conventional methods. Considering the large proportion of some species among clinical isolates, a strategy of initial screening with species-specific PCR (or AccuProbe assays) for the MTB complex and MAC, followed by direct sequencing of the strains that yield negative results, should make 16S rRNA sequencing more affordable for routine application in diagnostic laboratories.

Quantification of Influenza Virus RNA in Aerosols in Patient Rooms.

BACKGROUND: The potential for human influenza viruses to spread through fine particle aerosols remains controversial. The objective of our study was to determine whether influenza viruses could be detected in fine particles in hospital rooms. METHODS AND FINDINGS: We sampled the air in 2-bed patient isolation rooms for four hours, placing cyclone samplers at heights of 1.5m and 1.0m. We collected ten air samples each in the presence of at least one patient with confirmed influenza A virus infection, and tested the samples by reverse transcription polymerase chain reaction. We recovered influenza A virus RNA from 5/10 collections (50%); 4/5 were from particles>4 µm, 1/5 from 1-4 µm, and none in particles<1 µm. CONCLUSIONS: Detection of influenza virus RNA in aerosols at low concentrations in patient rooms suggests that healthcare workers and visitors might have frequent exposure to airborne influenza virus in proximity to infected patients. A limitation of our study was the small sample size. Further studies should be done to quantify the concentration of viable influenza virus in healthcare settings, and factors affecting the detection of influenza viruses in fine particles in the air.

An Asian study on the prevalence of atypical respiratory pathogens in community-acquired pneumonia.

BACKGROUND: In many parts of Asia, the inaccessibility and high cost of diagnostic tests have hampered the study of community-acquired pneumonia (CAP) caused by atypical respiratory pathogens. OBJECTIVE: This surveillance study examined the frequency of infection with Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila in 1756 patients presenting with signs and symptoms of CAP at 12 medical centres in Asia, using standardised laboratory techniques and interpretation criteria in all participating centres. METHODS: Diagnosis of current infection was based on significant changes in antibody titer or persisting high antibody titers, together with the presence of bacterial DNA in respiratory secretions, in the case of M. pneumoniae and C. pneumoniae infections, or bacterial antigen in urine, in the case of L. pneumophila serogroup 1 infection. RESULTS: Using these criteria, results from 1374 patients with paired sera showed that, overall, 23.5% of CAP cases were associated with infection with atypical respiratory pathogens, with M. pneumoniae, C. pneumoniae, and L. pneumophila being found in 12.2%, 4.7%, and 6.6% of cases, respectively. Persisting high antibody titers indicative of past exposure to M. pneumoniae, C. pneumoniae, and L. pneumophila were seen in 10.2%, 4.8%, and 18.9% of patients, respectively. CONCLUSION: These data reflect the overall high prevalence of these atypical pathogens among Asian patients with CAP.

Impact of the first hand sanitizing relay world record on compliance with hand hygiene in a hospital.

Staff of a large hospital in Hong Kong attempted and set the first Guinness World Record for the most participants in a hand sanitizing relay in May 2014. After this event, average compliance with hand hygiene increased from 72% (95% CI, 70%-74%) in 2013 to 85% (95% CI, 83%-87%) in June-July 2014, and the conceptual understanding of good hand hygiene practices improved.

Severe acute respiratory syndrome: scientific and anecdotal evidence for drug treatment.

Severe acute respiratory syndrome (SARS), caused by a highly infectious novel coronavirus (CoV), predominantly presents with severe pneumonitis leading to respiratory failure and death in approximately 10% of victims. Most cases present, after an incubation of 2 to 11 days, with fever and chills, which are followed by dry cough and dyspnea before the onset of respiratory failure. The management of SARS is controversial, largely due to the lack of data from controlled trials, which were logistically impossible to design or execute at the time of the overwhelming outbreak between March and June 2003. The use of an antiviral is logical although there is no effective agent against SARS-CoV, with the widespread use of ribavirin in 2003 attracting considerable scepticism. The use of ribavirin as a monotherapy in SARS is not recommended. Retrospective data suggest that administration of the anti-HIV drug Kaletra in combination with ribavirin could reduce mortality and incidence of respiratory failure. The use of corticosteroid was based on the similarity between SARS and bronchiolitis obliterans organizing pneumonia. Corticosteroid use is considered important in subsets of patients with SARS. As SARS may still resurge, it is imperative that past experience is analyzed. This review will attempt to address the rationale for pharmacotherapy in SARS using anecdotal and the limited published data.

Detection of katG Ser315Thr substitution in respiratory specimens from patients with isoniazid-resistant Mycobacterium tuberculosis using PCR-RFLP.

Mutations in the katG locus of catalase peroxidase in Mycobacterium tuberculosis (MTB) account for major isoniazid (INH) resistance. In the South China region, a collection of 906 respiratory specimens and 142 MTB isolates was used to evaluate the sensitivity and specificity of a PCR-RFLP method for the detection of INH resistance-associated mutations. Except for four catalase-negative MTB isolates, katG PCR for a 620-bp amplicon was successful for all purified MTB isolates. For respiratory specimens, diagnostic sensitivity and specificity of katG PCR was 85 and 100 %. Subsequent RFLP of the katG amplicons by MspI digestion identified that 51 % of INH-resistant MTB were associated with the Thr315 phenotype, and that codon 463 was a polymorphic site with no linkage to INH resistance. The Arg463 wild-type MTB isolates predominant in the Western world were replaced by isolates carrying Leu463 in the South China region. RFLP patterns of katG amplicons from respiratory specimens were identical to those of the corresponding MTB cultured colonies. This method has potential application for rapid diagnosis of INH resistance due to katG Ser315Thr mutation.

Determinants of an effective antibiotic campaign: Lessons from Hong Kong.

Hong Kong launched a publicity campaign on the use of antibiotics and antibiotic resistance in March/April 2011. Two population surveys were conducted in November 2010 (N=1569; response rate 69.2%) and June 2011 (N=1527; response rate 66.6%) before and after the campaign, respectively, to evaluate its impact. Adults aged ≥18 years were asked about their knowledge and attitude related to antibiotic use and antibiotic resistance. Information obtained from health professionals had the highest mean impact score. There was a significant increase in the proportion of respondents knowing that antibiotics could not cure influenza (from 58.0 to 65.0%; P<0.001) or viral infections (from 24.9 to 29.0%; P=0.002). Over one-quarter (27.7%) of respondents could recall the campaign, mostly through announcement of public interest (API) on television/radio. After regression analysis, age, personal hygiene practices in daily life, and the attitude that everyone had a role to play in alleviating the problem of antimicrobial resistance were found to be associated with campaign awareness.