Risk reduction analysis of mix-and-match vaccination strategy in healthcare workers during SARS-CoV-2 Omicron variant predominant period: A multi-center cohort study in Taiwan.

This study investigated the relative effectiveness of a mix-and-match vaccination strategy, primarily comprising ChAdOx1 nCOV-19, mRNA-1273, BNT162b2, and a protein-based vaccine, MVC-COV1901, against COVID-19 in a healthcare worker (HCW) cohort in Taiwan during a period when the Omicron variant was predominant. The analysis included a total of 21,729 HCWs and recorded 3,672 infections with no severe disease nor death. Two main findings were observed from the study. Firstly, for those with ChAdOx1 nCOV-19 as primary series, a booster dose with BNT162b2 was associated with a small decrease in the risk of acquiring infection compared to those with mRNA-1273 as a booster (Adjust hazard ratio [Adj HR] 0.864; 95% confidence interval [CI] 0.761‒0.981, P = .024). Secondly, for HCWs receiving an mRNA-1273 booster, compared to those receiving ChAdOx1 nCOV-19 as the primary series, mixed primary series and homologous mRNA-1273 primary series were associated with a higher (Adj HR 1.144; 95% CI 1.021‒1.282, P = .021) and lower risk (Adj HR 0.735; 95% CI 0.671‒0.805, P < .001) of acquiring infection, respectively. Our study demonstrated that mix-and-match vaccination strategy may be associated with different level of risk reduction in acquiring infection, and sizable, prospective studies are encouraged to further elucidate our observation.

Clinical Features, Antimicrobial Resistance, and Serogroups of Nontyphoidal Salmonella Isolated From Infants Less Than 3 Months Old in the Recent Decade.

BACKGROUND: Antibiotic treatment is indicated for infants with nontyphoidal Salmonella (NTS) enterocolitis. However, whether antimicrobial resistance (AMR) is a problem among young infants is unknown. This study investigated the characteristics of NTS infections in young infants. METHODS: Infants less than 3 months old with NTS infections were enrolled and grouped into 2 cohorts (diagnosed 2010-2015 or 2016-2021). Salmonella isolated from blood or cerebrospinal fluid was defined as invasive NTS (iNTS). The clinical features, AMR and serogroups were compared between cohorts. RESULTS: In total, 102 young infants had NTS infections, 6.9% of which were iNTS. Infants with iNTS infections were younger, hospitalized longer, and received longer antibiotic courses. More than half of cases of iNTS were resistant to ciprofloxacin, ceftriaxone and greater than or equal to 3 antibiotics. iNTS was mainly observed in Salmonella groups C2 and E. Over the past decade, group B (44%), group E (26%) and group C2 (16%) have been the most common serogroups. NTS significantly increased AMR to ciprofloxacin, ceftriaxone and trimethoprim-sulfamethoxazole, and greater than or equal to 3 antibiotics. Both multidrug resistance and extensive drug resistance in NTS also significantly increased. CONCLUSIONS: The serogroups varied with time, and the main causes of iNTS, groups C2 and E, increased over the past decade. The prevalence of AMR also increased, especially for iNTS. Given the low iNTS rate and high AMR, routine antibiotic use among infants with NTS infections between 1 and 3 months old should be reconsidered. Further large-scale research is required to formulate therapeutic strategies.

Prevalence, Serotypes, and Antimicrobial Resistance Patterns of Non-Typhoid Salmonella in Food in Northern Taiwan.

Salmonella is one of the most common bacteria causing food poisoning worldwide. We evaluated the prevalence, the serotypes, and the antimicrobial resistance (AMR) of Salmonella isolates from many kinds of food, particularly pork and chicken in retail, in Taiwan between January 2017 and December 2019. The E-test was used to assess antimicrobial susceptibility and a polymerase chain reaction was performed for serotyping. A total of 459 different foods were investigated, and 117 Salmonella strains were isolated. Retail pork and chicken were the most common Salmonella-contaminated foods (64.1% and 29.1%, respectively). Of the 117 isolates, 23 serotypes were identified. The serotypes Derby (16.2%), Anatum (13.7%), and Agona (8.5%) were the most prevalent. The resistance rates to ciprofloxacin, ceftriaxone, and carbapenem were 41.9%, 11.1%, and 1.7%, respectively. The Derby and Anatum serotypes were prevalent in chicken and pork; the Anatum serotype had significantly higher ciprofloxacin and ceftriaxone resistance rates and was highly prevalent in 2017 and 2018. Multi-locus sequence typing analysis revealed that the 58 randomly chosen Salmonella isolates belonged to 18 sequence types (STs). ST64 (Anatum, 16 out of 58, 27.6%) was the most common, followed by ST321 (Muenster, 6/58, 10.3%), ST831 (Give, 5/58, 8.6%), ST155 (London, 4/58, 6.9%) and ST314 (Kentucky, 4/58, 6.9%). Multidrug-resistant Salmonella strains were remarkably observed in the serotypes Anatum (ST64) and Goldcoast (ST358). This study revealed that retail pork was commonly contaminated with antimicrobial-resistant Salmonella. Thus, periodic investigations of Salmonella serotypes and AMR are needed.

Emergence and spread in Taiwan of multidrug-resistant serotypes of nontyphoidal Salmonella.

PURPOSE: Antimicrobial resistance of nontyphoidal Salmonella (NTS) is a threat to public health worldwide. METHODS: A study on longitudinally collected NTS isolates from a medical center in Taiwan from 2011 to 2019 was undertaken. The multidrug resistance (MDR) and extensively drug resistance (XDR) phenotypes were determined according to internationally used definitions. Molecular serotyping was performed on the resistant NTS. RESULTS: Notably 16.1% (870/5412) of the isolates were MDR, while XDR accounted for 2.1% (111/5412). Both MDR and XDR NTS have increased significantly from 2011 to 2019, especially from 2015 to 2017 (MDR from 9.6% in 2015 to 23.1% 2017; XDR from 1.4% in 2016 to 4.7% in 2017). S. Anatum was the commonest NTS serotype expressing MDR and XDR, in 256/559 (45.8%) and 81/111 (73.0%) of the isolates, respectively, followed by S. Typhimurium and S. Goldcoast. Children < 18 years old contributed to 69.0% of all MDR cases and 64.0% of all XDR cases; majority of them aged less than 5 years. CONCLUSIONS: Increasing MDR and XDR NTS is a threat to public health. MDR and XDR NTS usually caused gastroenteritis in children < 5 years old. Multiple NTS serotypes expressing MDR and XDR indicate multiple food vehicles involved in the transmission. Proper food hygiene practice should never be over-reinforced.

Microbiological and genomic investigations of invasive Salmonella enterica serovar Panama from a large outbreak in Taiwan.

BACKGROUND/PURPOSE: Salmonella Panama was considered an invasive non-typhoidal Salmonella (iNTS) serovar. Comprehensive clinical, microbiological, and genomic studies on S. Panama are scarce. We aimed to characterize the clinical and microbiological characteristics of S. Panama infection. Virulence mechanism of S. Panama and other iNTS serovars were also examined. METHODS: Based on data from the longitudinal surveillance system for Salmonella deployed in Taiwan since 2004, a case-control study was undertaken to evaluate clinical characteristics of S. Panama infection during an outbreak in 2015-2016. Cellular experiments were conducted to compare pathogenicity of S. Panama and other iNTS with S. Typhimurium. RESULTS: Most patients (41/44, 93.2%) infected by S. Panama were <5 years old (median, 1.3 years). The case-control study showed that 28 out of the 41 (68.3%) manifested as bacteremia, compared to S. Typhimurium (11.1%). Patients infected by S. Panama had longer durations of fever (P = 0.005) and hospitalization (P < 0.001). Genomic analyses split the isolates into three clades: two clones caused the outbreak, whereas another one accounted for the sporadic infections before 2015. Cellular experiments revealed that S. Panama and other iNTS serovars showed higher monolayer penetration and intracellular survival within macrophages, compared to S. Typhimurium. CONCLUSION: This study confirmed that S. Panama is a clinically invasive serovar. Different iNTS serovars express common virulence phenotypes, but they may acquire invasiveness through distinct expression or combinations of virulence genes.

Characterization and Source Investigation of Multidrug-Resistant Salmonella Anatum from a Sustained Outbreak, Taiwan.

An ongoing outbreak of multidrug-resistant Salmonella enterica serovar Anatum began in Taiwan in 2015. Pork and poultry were identified as vehicles for transmission. Contaminated meat contributed to the high rate of infections among children. Nearly identical Salmonella Anatum strains have been identified in the United Kingdom, the United States, and the Philippines.

Highly antimicrobial-resistant Nontyphoidal Salmonella from retail meats and clinical impact in children, Taiwan.

BACKGROUND: The epidemiology of nontyphoidal Salmonella (NTS) resistant to ciprofloxacin or ceftriaxone and its impact on patients' clinical course are rarely reported. METHODS: Children with culture-proven salmonellosis treated in a medical center in northern Taiwan in 2017 were enrolled. To trace the source of Salmonella, Salmonella isolated from food samples were collected from markets. Antimicrobial susceptibility and serotypes were determined. RESULTS: Among the 453 isolates, 122 (26.9%) were highly antimicrobial-resistant, as defined by resistance to ciprofloxacin or ceftriaxone or both. The most prevalent highly resistant serotype was S. Anatum (66, 54.1%). Salmonella was detected in 94.1%, 66.7%, and 8.6% of examined pork, chicken, and vegetables examined, respectively. S. Anatum (6, 21.4%) and S. Derby (6, 21.4%) were the major serotypes isolated. Majority of the S. Anatum (5, 83.3%) were highly antimicrobial-resistant. More patients infected by highly resistant Salmonella required carbapenem treatment (OR = 23.5, 95% confidence interval [CI] 2.8-192.7, P < 0.001). Patients with ceftriaxone-resistant NTS infections had a significantly longer hospital stay than others (P < 0.001). Totally, 34 (7.5%) presented with invasive diseases (31 bacteremia, 1 intestinal perforation, 1 toxic megacolon and 1 septic arthritis). Risk factors for invasive disease included prolonged fever for ≧5 days and infection occurring in warmer season from May to October. The rise of ambient temperature in northern Taiwan was associated with increasing Salmonella infections. CONCLUSIONS: Retail meats were the main source of highly antimicrobial-resistant NTS in northern Taiwan. Highly antimicrobial resistance significantly impacted the clinical course and treatment of children with NTS infection.

Emergence and Evolution of High-Level Cephalosporin-Resistant Salmonella Goldcoast in Northern Taiwan.

BACKGROUND: Nontyphoidal Salmonella (NTS) is an important foodborne pathogen worldwide. We investigated a 2018 outbreak of highly antimicrobial-resistant Salmonella enterica serotype Goldcoast in northern Taiwan. METHODS: We collected 30 clinical isolates and 2 meat isolates from this outbreak in New Taipei and Taoyuan, Taiwan in 2018. The clinical manifestations and the treatment of the patients were reviewed. To trace the source, we examined NTS isolated from food samples collected from the markets in northern Taiwan. All of the isolates along with an additional human isolate from China were sequenced and compared with the sequences of Salmonella Goldcoast reported by other countries. RESULTS: The outbreak involved 14 pediatric patients (<5 years old) and 16 adults (36 to 83 years old). Nine patients with invasive or severe disease required carbapenem treatment. The MIC90 of ceftriaxone and ciprofloxacin for the outbreak isolates was >256 µg/mL and 1 µg/mL, respectively, and a conjugative 278-kilobase plasmid harboring bla CTX-M-55 and qnrS1 contributed towards the resistance. Whole-genome sequencing revealed a clonal relationship among the outbreak isolates and the 2 collected from the retail meats. The outbreak clone was phylogenetically close to that of Salmonella Goldcoast reported in the United Kingdom, Poland, and China, whereas similar resistance plasmids were found in China and Cambodia. CONCLUSIONS: The clinical spectrum of the high-level cephalosporin-resistant Salmonella Goldcoast is similar to that of other NTS serotypes, but severe cases required carbapenem treatment. The study confirmed the emergence of a highly antimicrobial-resistant clone of Salmonella Goldcoast, highlighting the importance of surveillance for food safety.

Recombinant chimeric vaccine composed of PRRSV antigens and truncated Pseudomonas exotoxin A (PE-K13).

A Pseudomonas exotoxin (PE-KDEL)-based chimeric subunit vaccine system was recently developed using a reverse vaccinology technique. In this study, the plasmids containing PE-PRRS chimeric subunits were constructed that composed of porcine reproductive and respiratory syndrome virus (PRRSV) antigen moieties, a ligand moiety and a Pseudomonas exotoxin A deleted domain III (PE (ΔIII)), and a carboxyl terminal moiety that includes a polypeptide with amino acid sequence KDEL (K3). The PE-PRRS combination vaccine can effectively induce not only PRRSV-specific INF-γ cellular immunity but also a slow-reacting and complement-requiring type serum neutralizing antibody in pigs. In a specific pathogen free (SPF) pig challenge model, body temperature (colonic temperature), occurrence of PRRSV viremia, nasal excretions, gross and histopathological appearances of pneumonia, and serum antibody activity (IFA and SN) titers significantly differed between the immunized group and the control group. The survey showed that a 0.3mg/dose PE-PRRS vaccine formula conferred protection against PRRSV. A field trial of PE-PRRS vaccine was performed to study the immune response of pregnant sows after vaccination in a PRRSV persist farm. The RT-PCR analysis of viremia and serological titers showed that the PE-PRRS vaccine not only increased sow reproductive performance and evoked its immune response to PRRS viremia, it also activated maternal immune protections to prevent piglets from inflicting viremia. In conclusion, we developed a novel and effective PRRS cytotoxic T-cells (CTLs)-based vaccine containing Pseudomonas exotoxin (PE-KDEL) carrier in combination with PRRSV conserved epitopes against PRRS virus.