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Abstract Background Staphylococcus aureus is one of the most important bacteria in human colonization and infection. Clonal complex1 (CC1) is one of the largest and most important S. aureus CCs, and it is a predominant clone in S. aureus colonization and can cause a series of S. aureus infections including bloodstream infections. No studies on the relationship of CC1 S. aureus between colonization and infection have been published. Methods To figure out if there are some significant factors in CC1 S. aureus help its colonization or infection, 15 CC1 S. aureus isolates including ten from colonization and five from bloodstream infections were enrolled in this study. Whole-genome sequencing and bioinformatics analysis were performed. Results Virulence factor regulators XdrA, YSIRK signal peptide, CPBP family and OmpR family specifically found in infection isolates can promote virulence factors and enhance the pathogenicity of S. aureus. In addition, some significant differences in metabolism and human diseases were discovered between colonization and infection. Fst family of type I toxin–antitoxin system that mainly maintains stable inheritance was specifically found in CC1 S. aureus colonization isolates and might help S. aureus survive for colonization. No significant differences in genomic evolutionary relationship were found among CC1 S. aureus isolates between colonization and infection. Conclusions Virulence factor regulators and metabolic state can promote CC1 S. aureus pathogenic process compared with colonization, and it seems that the strains of colonization origin cannot have pathogenic potential. Experimental confirmation and a bigger number of CC1 S. aureus strains are necessary for further study about the details and mechanism between colonization and infection.

BackgroundPseudomonas aeruginosa (P. aeruginosa) accounts for high antimicrobial resistance and mortality rates of bloodstream infections (BSIs). We aim to investigate incidence, antimicrobial resistance and risk factors for mortality of P. aeruginosa BSIs among inpatients.MethodsA retrospective cohort study were conducted at two tertiary hospitals in 2017–2021. Medical and laboratory records of all inpatients diagnosed with P. aeruginosa BSIs were reviewed. A generalized linear mixed model was used to identify risk factors for mortality.ResultsA total of 285 patients with P. aeruginosa BSIs were identified. Incidence of P. aeruginosa BSIs fluctuated between 2.37 and 3.51 per 100,000 patient-days over the study period. Out of 285 P. aeruginosa isolates, 97 (34.04%) were carbapenem-resistant (CR) and 75 (26.32%) were multidrug-resistant (MDR). These isolates showed low resistance to aminoglycosides (9.51–11.62%), broad-spectrum cephalosporins (17.19–17.61%), fluoroquinolones (17.25–19.43%), and polymyxin B (1.69%). The crude 30-day mortality rate was 17.89% (51/285). Healthcare costs of patients with MDR/CR isolates were significantly higher than those of patients with non-MDR/CR isolates (P < 0.001/=0.002). Inappropriate definitive therapy [adjusted odds ratio (aOR) 4.47, 95% confidence interval (95% CI) 1.35–14.77; P = 0.014], ICU stay (aOR 2.89, 95% CI: 1.26–6.63; P = 0.012) and corticosteroids use (aOR 2.89, 95% CI: 1.31–6.41; P = 0.009) were independently associated with 30-day mortality.ConclusionIncidence of P. aeruginosa BSIs showed an upward trend during 2017–2020 but dropped in 2021. MDR/CR P. aeruginosa BSIs are associated with higher healthcare costs. Awareness is required that patients with inappropriate definitive antimicrobial therapy, ICU stay and corticosteroids use are at higher risk of death from P. aeruginosa BSIs.

Background: Infection is the predominant contributor to morbidity and mortality in burn patients, and burn wound infection (BWI) is the most common reason. The objective of this research was to analyze the incidence, factors and progression of BWI, in terms of events and bacteria. Methods: Clinical variables of all qualified patients admitted to burn wards were analyzed retrospectively in 2021 at a tertiary hospital in eastern China through univariate analysis and multivariate logistic regression. The Kaplan–Meier method was also used for plotting survival curves. Isolates and resistance data were evaluated to demonstrate the evolution of targeted antibiotics of strains from BWI. Results: A total of 580 (median age, 39.5 years (23–56 years); 372/580 (64.14%) male) patients were evaluated, 348 (60.0%) of whom experienced BWI. A variety of factors are associated with BWI. Multivariate logistic regression analysis showed that depth and area of burn and duration from burn to first hospitalization are independent risk factors for BWI. For BWI onset in these patients, 47.24% (274/580) occurred in the first week. The most frequently isolated causative organism was Staphylococcus aureus (15.7%) in patients with BWI. The duration of transition from Gram-positive strains (median 3 days, (2–7 days)) to Gram-negative (median 10 days, (4–17 days)) ones isolated from burn wound shrunk. Hospital length of stay was considered as a protective factor for BWI. Conclusion: The precise assessment of factors affecting BWI in burn patients enhances prompt and suitable management. Swab cultures for surveillance could be utilized to monitor the microbiological status of burn patients.

In order to develop a new type of antioxidants with high efficiency, a series of β-ionone thiazolylhydrazone derivatives were designed and synthesized from β-ionone, and their structures were characterized by 1H-NMR, 13C-NMR, FT-IR, and HR-MS. The antioxidant test in vitro indicated that most of the target compounds had high biological activity. Among them, compound 1k exhibited very strong DPPH (1,1-diphenyl-2-picrylhydrazyl radical)-scavenging activity with a half-maximal effective concentration (IC50) of 86.525 μM. Furthermore, in the ABTS (2,2-azinobis (3-ethylbenzothiazoline-6-sulfonate) diammonium salt)-scavenging experiment, compound 1m exhibited excellent activity with an IC50 of 65.408 μM. Their biological activities were significantly better than those of the positive control Trolox. These two compounds, which have good free-radical-scavenging activity in vitro, were used as representative compounds in the anti-browning experiment of fresh-cut potatoes. The results showed that 1k and 1m had the same anti-browning ability as kojic acid, and they were effective browning inhibitors. In addition, it is well known that microbial infection is one of the reasons for food oxidation. Therefore, we investigated the antifungal activity of 25 target compounds against eight plant fungi at a concentration of 125 mg/L. The results indicated that these compounds all have some antifungal activity and may become new potential fungicides. Notably, compound 1u showed the best inhibitory effect against Poria vaporaria, with an inhibition rate as high as 77.71%; it is expected to become the dominant structure for the development of new antifungal agents.

In this paper, four new compounds with quinazolinone structure were designed and synthesized based on the special biological activity of quinazolinone. The four new compounds containing quinazolinone structures were synthesized using a one-pot method after intramolecular cyclization and dehydration catalyzed by aqueous methylamine solution. Their structures were characterized using 1H NMR, 13C NMR, FT-IR, and HRMS, and the crystal structure of 2a was characterized using X-ray diffraction. In their potential antifungal activity tests, it was found that the four newly synthesized compounds exhibited significant antifungal activity against all seven phytopathogenic fungi at concentrations of 150 and 300 mg/L. Among them, the target compound 2c showed the best inhibitory effect against Fusarium oxysporum f. sp. Niveum fungus, with 62.42% inhibition at a concentration of 300 mg/L. Compound 2c is expected to be a leading compound for the treatment of watermelon Fusarium wilt in the future, which is worth further study.

Abstract Background Staphylococcus aureus is the most dominant human pathogen, responsible for a variety of chronic and severe infections. There is mounting evidence that persisters are associated with treatment failure and relapse of persistent infections. While some essential oils were reported to have antimicrobial activity against growing S. aureus, activity of essential oils against the stationary phase S. aureus enriched in persisters has not been investigated. Methods In this study, we evaluated the activity of 143 essential oils against both growing and stationary phase S. aureus by minimum inhibitory concentration (MIC) testing and by colony forming unit assay. Results We identified 39 essential oils (Oregano, Cinnamon bark, Thyme white, Bandit “Thieves”, Lemongrass (Cymbopogon flexuosus), Sandalwood oil, Health shield, Allspice, Amyris, Palmarosa, Cinnamon leaf, Clove bud, Citronella, Geranium bourbon, Marjoram, Peppermint, Lemongrass, Cornmint, Elemi, Ho wood, Head ease, Lemon eucalyptus, Litsea cubeba, Myrrh, Parsley seed, Coriander oil, Dillweed, Hyssop, Neroli, Rosewood oil, Tea tree, Cajeput, Clove bud, Lavender, Sleep tight, Vetiver, Palo santo, Sage oil, Yarrow) at 0.5% (v/v) concentration, 10 essential oils (Cinnamon bark, Oregano, Thyme white, Bandit “Thieves”, Lemongrass, Sandalwood oil, Health shield, Allspice, Amyris, Palmarosa at 0.25% (v/v) concentration, and 7 essential oils (Oregano, Cinnamon bark, Thyme white, Lemongrass, Allspice, Amyris, Palmarosa at 0.125% (v/v) concentration to have high activity against stationary phase S. aureus with no visible growth on agar plates after five-day exposure. Among the 10 essential oils which showed high activity at 0.25% (v/v) concentration, 9 (Oregano, Cinnamon bark, Thyme white, Bandit “Thieves”, Lemongrass, Health shield, Allspice, Palmarosa, Amyris showed higher activity than the known persister drug tosufloxacin, while Sandalwood oil had activity at a higher concentration. In Oregano essential oil combination studies with antibiotics, Oregano plus tosufloxacin (or levofloxacin, ciprofloxacin) and rifampin completely eradicated stationary phase S. aureus cells, but had no apparent enhancement for linezolid, vancomycin, sulfamethoxazole, trimethoprim, azithromycin or gentamicin. Conclusions Our findings indicate that some essential oils have excellent activity against both growing and stationary phase S. aureus. Further studies are needed to identify the active components, evaluate safety, pharmacokinetics, and their activity to eradicate S. aureus infections in vivo.

Background: Bloodstream infections are recognized as important nosocomial infections. Escherichia coli (E. coli) is the most prevalent Gram-negative bacillary pathogen causing bloodstream infections (BSIs). This retrospective study investigated drug susceptibility and molecular epidemiology of E. coli isolated from patients with BSI in Shanghai, China.Methods: We collected E. coli isolated from the blood cultures of patients with BSI between January 2016 and December 2019. We randomly selected 20 strains each year to investigate antimicrobial resistance, resistance genes, and molecular epidemiological characteristics. Antimicrobial susceptibility testing was performed by the disk diffusion method. PCR was performed to detect extended-spectrum β-lactamases (ESBLs), carbapenemase genes, and housekeeping genes, and phyloviz was applied to analyze multilocus sequence typing (MLST).Results: Penicillins, first- and second-generation cephalosporins and fluoroquinolones have high resistance rates (>60%). Among the 80 randomly selected strains, 47 (58.8%) produced ESBLs, and one produced carbapenemase. Sequencing of resistance genes identified blaCTX−M−14 (34%, 16/47), blaCTX−M−15 (23.4%, 11/47) and blaCTX−M−27 (14.8%, 7/47) as the most prevalent genotypes of ESBLs. ST131 (14/80) was the most prevalent sequence type (ST), followed by ST1193 (10/80), ST648 (7/80).Conclusions: Our findings suggest that amikacin, carbapenems, and piperacillin-tazobactam have relatively low resistance rates and may be the preferred antibiotic regimens for empiric therapy. ST131 and blaCTX−M−14 are still the main prevalent in Shanghai with a rapid increase in the occurrence of ST1193 is rapidly increasing and more diverse blaCTX genes.

Background: Bloodstream infections (BSIs) are recognized as important nosocomial infections. Klebsiella pneumoniae is one of the major causes of bacteremia. This retrospective study focused on drug susceptibility and molecular epidemiology of K. pneumoniae isolated from intensive care unit (ICU) patients with BSI in Shanghai, China.Methods: Consecutive K. pneumoniae isolates were collected from ICU patients. Antibiotic susceptibility testing was conducted by the broth microdilution method. PCR was performed to detect antimicrobial resistance genes. We also completed multilocus sequence typing (MLST) and GoeBURST was used to analyze the result of MLST.Results: A total of 78 K. pneumoniae isolates were enrolled. K. pneumoniae from ICU-BSIs were highly resistant to almost all common antibiotics. The most frequent resistance determinants responsible for extended-spectrum β-lactamase (ESBL) producers were blaCTX−M−14, blaCTX−M−15, and blaCTX−M−55. KPC was the only enzyme, which was detected by the carbapenemase producers. The most principal sequence types (STs) were ST11, ST15, and ST23.Conclusion: This study presents for the first time the antibiotic resistance phenotype and molecular epidemiology of K. pneumoniae isolated from ICU patients with BSIs in Shanghai. ICU-BSI K. pneumoniae is characteristic of a high resistance rate. The occurrence of the KPC-2 enzyme may result from nosocomial clonal dissemination of ST11 K. pneumoniae.

Urinary tract infection (UTI) is one of the most common bacterial infections and UTI is the most common extraintestinal infectious disease entity in women worldwide. Uropathogenic Escherichia coli (UPEC) is the leading cause of UTI. While antimicrobial resistance has emerged as one of the principal problems of UTI, little is known about the epidemiology of UPEC isolated from female patients in Shanghai. This study aimed to describe the antimicrobial resistance and molecular epidemiology of UPEC isolated from female patients in Shanghai, China. UPEC isolates were collected from female patients from July 2019 to June 2020 in Shanghai and a total of 151 isolates were obtained randomly. Antimicrobial susceptibility testing was performed using the disk diffusion method. Multilocus sequencing type, phylogenetic groups, antimicrobial resistance genes, and virulence genes were detected by polymerase chain reaction. In our study, no carbapenem-resistant isolates were found, but fluoroquinolone-resistant and multi-drug resistant UPEC accounted for 62.25% and 42.38%, respectively. The phylogenetic group B2 (58.94%) predominated, followed by phylogenetic group D (26.49%). The most prevalent sequence type was ST1193 (25.83%), which was first reported in Shanghai. The rate of extended-spectrum β-lactamase (ESBL)-positive isolates was 39.74% and the dominant ESBL genotype was blaCTX-M-14 (21/60), followed by blaCTX-M-55 (12/60). Mutations in gyrA were detected in the majority of fluoroquinolone-resistant isolates (90/94), followed by parC (85/94) and parE (71/94). The aac (3) -IIa was also found in 85% of aminoglycoside resistance isolates. Among 151 UPEC isolates, the common virulence genes were csgA (97.35%), fimH (92.72%), sitA (82.12%), and malX (65.56%). In conclusion, the high antimicrobial resistance of UPEC isolated from female patients, harboring a series of virulence genes, are troublesome for medical practitioners in Shanghai. At present, the prevalent ST1193 and emerging blaCTX-M-55 make UTI therapy more challenging.

Background: Streptococcus pneumoniae, which cause noninvasive pneumococcal diseases, severely impair children's health. This study analyzed serotype distribution and antimicrobial resistance of S. pneumoniae from January 2012 to December 2012 in a Children's Hospital, Shanghai. Methods: A total of 328 pneumococcal isolates were serotyped by multiplex sequential PCR and/or capsule-quellung reaction. The minimum inhibitory concentrations for 11 antimicrobial agents were determined by broth microdilution method. Results: Among 328 strains, 19F (36.3%), 19A (13.4%), 6A (11.9%), 23F (11.0%), 14 (5.8%), 6B (5.2%), and 15B/C (4.3%) were the most common serotypes. The coverage rates of 7-, 10-, and 13-valent conjugate vaccines (PCV7, PCV10, and PCV13) were 58.2%, 58.2%, and 84.1%, respectively. Out of the isolates, 26 (7.9%) strains were penicillin resistant. Most of the strains displayed high resistance rate to macrolides (98.5% to erythromycin, 97.9% to azithromycin, and 97.0% to clindamycin). Conclusions: The potential coverage of PCV13 is higher than PCV7 and PCV10 because of the emergence of 19A and there should be long-term and systematic surveillance for non-vaccine serotypes. Keywords: Streptococcus pneumoniae, Serotype, Antimicrobial resistance

Bartonella henselae can cause various infections in humans, ranging from benign and self-limiting diseases to severe and life-threatening diseases as well as persistent infections that are difficult to treat. To develop more effective treatments for persistent Bartonella infections, in this study, we performed a high-throughput screen of an FDA-approved drug library against stationary phase B. henselae using the SYBR Green I/propidium iodide (PI) viability assay. We identified 110 drug candidates that had better activity against stationary phase B. henselae than ciprofloxacin, and among the top 52 drug candidates tested, 41 drugs were confirmed by microscopy to have higher activity than the current frontline antibiotic erythromycin. The identified top drug candidates include pyrvinium pamoate, daptomycin, methylene blue, azole drugs (clotrimazole, miconazole, sulconazole, econazole, oxiconazole, butoconazole, bifonazole), aminoglycosides (gentamicin and streptomycin, amikacin, kanamycin), amifostine (Ethyol), antiviral Lopinavir/ritonavir, colistin, nitroxoline, nitrofurantoin, verteporfin, pentamidine, berberine, aprepitant, olsalazine, clinafloxacin, and clofoctol. Pyrvinium pamoate, daptomycin, methylene blue, clotrimazole, and gentamicin and streptomycin at their respective maximum drug concentration in serum (Cmax) had the capacity to completely eradicate stationary phase B. henselae after 3-day drug exposure in subculture studies. While the currently used drugs for treating bartonellosis, including rifampin, erythromycin, azithromycin, doxycycline, and ciprofloxacin, had very low minimal inhibitory concentration (MIC) against growing B. henselae, they had relatively poor activity against stationary phase B. henselae, except aminoglycosides. The identified FDA-approved agents with activity against stationary phase B. henselae should facilitate development of more effective treatments for persistent Bartonella infections.

Streptococcus pneumoniae is a common pathogenic cause of pediatric infections. This study investigated the serotype distribution, antimicrobial susceptibility, and molecular epidemiology of pneumococci before the introduction of conjugate vaccines in Shanghai, China.A total of 284 clinical pneumococcal isolates (270, 5, 4,3, and 2 of which were isolated from sputum, bronchoalveolar lavage fluid, blood, cerebral spinal fluid, and ear secretions, respectively) from children less than 14 years of age who had not been vaccinated with a conjugate vaccine, were collected between January and December in 2013. All isolates were serotyped by multiplex polymerase chain reaction or quellung reactions and antimicrobial susceptibility testing was performed using the broth microdilution method. The molecular epidemiology of S.pneumoniae was analyzed by multilocus sequence typing (MLST).Among the 284 pneumococcal isolates, 19F (33.5%), 19A (14.1%), 23F (12.0%), and 6A (8.8%) were the most common serotypes and the coverage rates of the 7-, 10-, and 13-valent pneumococcal conjugate vaccines (PCV7, PCV10, and PCV13) were 58.6%, 59.4% and 85.1%, respectively. Antimicrobial susceptibility showed that the prevalence rates of S.pneumoniae resistance to penicillin were 11.3% (32/284). Approximately 88.0% (250/284) of the isolates exhibited multi-drug resistance. MLST analysis revealed a high level of diversity, with 65 sequence types (STs) among 267 isolates. Specifically, the four predominant STs were ST271 (24.3%, 65/267), ST320 (11.2%, 30/267), ST81 (9.7%, 26/267), and ST3173 (5.2%, 14/267), which were mainly associated with serotypes 19F, 19A, 23F, and 6A, respectively.The prevalent serotypes among clinical isolates from children were 19F, 19A, 23F, and 6A and these isolates showed high resistance rates to β-lactams and macrolides. The Taiwan19F-14 clone played a predominant role in the dissemination of pneumococcal isolates in Shanghai, China. Therefore, continued and regional surveillance on pneumococcal isolates may be necessary.