Pseudomonas aeruginosa High-Risk Sequence Type 463 Co-Producing KPC-2 and AFM-1 Carbapenemases, China, 2020-2022.

We report the clonal spread and evolution of high-risk Pseudomonas aeruginosa sequence type 463 co-producing KPC-2 and AFM-1 carbapenemases isolated from hospital patients in China during 2020-2022. Those strains pose a substantial public health threat and surveillance and stricter infection-control measures are essential to prevent further infections.

Clinical and microbiological characteristics of carbapenem-resistant Enterobacteriaceae causing post-operative central nervous system infections in China.

OBJECTIVES: Postoperative central nervous system infections (PCNSIs) caused by carbapenem-resistant Enterobacteriaceae (CRE) frequently result in unfavourable outcomes. However, CRE PCNSIs have not been well described from a clinical and microbiological perspective. METHODS: A total of 254 PCNSIs cases were included (January 2017 through June 2020), and clinical features were compared based on pathogenic classification. Cox regression analysis was performed to assess risk factors for mortality. Antibiotic susceptibility testing and whole genome sequencing were conducted on CRE isolates preserved. MLST, cgMLST, resistance genes and virulence genes were further analysed. RESULTS: Among 254 PCNSI cases, 15.4% were caused by Enterobacteriaceae including 28 cases by CRE. The 28-day mortality rates for CRE, CSE and non-Enterobacteriaceae PCNSIs were 50.0%, 27.3%, and 7.4%, respectively. 42.9% (12/28) of the CRE PCNSIs patients achieved clinical cure, with 25.0% achieved microbiological clearance. ST11-KL64 carrying blaKPC-2 was dominant in CRE (17/23, 73.9%), and the 28-day mortality rate of its infection was 58.5%. Most CRKP carried rampA/rampA2 genes (17/23, 73.9%). CONCLUSION: ST11-KL64 CRKP carrying blaKPC-2 dominated among CRE PCNSIs. Targeted anti-infective combination therapy based on ceftazidime/avibactam or amikacin, combined with intrathecal administration of amikacin, was found to be effective. These findings render a new insight into the clinical and microbiological landscape of CRE PCNSIs.

Risk factors and outcomes of inpatients with carbapenem-resistant Pseudomonas aeruginosa bloodstream infections in China: a 9-year trend and multicenter cohort study.

Objective: Bacteremia caused by carbapenem-resistant Pseudomonas aeruginosa (CRPA) has high mortality, threatening the healthcare quality worldwide. Analysis is required to update the epidemiological data of CRPA bloodstream infections (BSI) and evaluate the prevalent strains in China. Moreover, it is necessary to clarify the risk factors associated with the development and mortality of CRPA bacteremia. Methods: This is a 9-year multicenter retrospective study, enrolling 137 patients with CRPA BSI and 137 carbapenem-susceptible P. aeruginosa (CSPA) BSI during January 2012 and December 2020. Antimicrobials susceptibility between the two groups were compared. Risk factors of CRPA BSI were identified by binary logistic regression for development and cox regression for mortality. The Kaplan-Meier method was used to compare time to mortality. CRPA and difficult-to-treat resistant P. aeruginosa (DTRPA) detection rate was analyzed year-by-year in ZYH. Results: A total of 7,384 P. aeruginosa clinical samples were cultured in ZYH during 9 years, and notable increase of CRPA and DTRPA detection rate in P. aeruginosa BSI was identified (from 17 to 60%; from 2.1 to 25%). Multivariate analysis revealed that prior ICU hospitalization, immunosuppressive therapy and exposure to carbapenems were independent risk factors for development of CRPA BSI. The 30-day crude mortality of 137 CRPA BSI was 39%. A total of 46 DTRPA were identified, and the 30-day mortality for patients infected by DTRPA was 50%. The 30-day crude mortality of CRPA BSI was independently associated with multiple organ failure and higher Pitt bacteremia score, whereas receipt appropriate therapy improved prognosis. Conclusion: A significant increase in the detection rate of CRPA and DTRPA in P. aeruginosa BSI was identified. Strict policies for carbapenems usage, cautious decisions regarding the usage of immunosuppressive agent and standard care for patients with prior ICU hospitalization are necessary for CRPA BSI management.

Environmental Monitoring of Parvovirus B19 in the Kidney Transplantation Ward of a Chinese Teaching Hospital.

Purpose: Parvovirus B19 (B19V) infection is a viral threat after kidney transplantation. It is mainly transmitted by close-contact inhalation of aerosolized viral particles. The risk of nosocomial spread of B19V in the transplantation ward is quite high. This study aimed to evaluate the quality of routine disinfection and the effectiveness of isolation measures in the wards of B19V-infected kidney transplant recipients. Patients and Methods: Throat swab samples of 19 kidney transplant recipients admitted to the isolation ward and three healthcare workers (HCWs) were collected for viral DNA detection. Routine disinfection procedures were performed twice a day in general and B19V isolation wards. Environmental surface and air samples were collected for viral DNA detection before and after disinfection. Results: A total of four patients were diagnosed with B19V infection and transferred to the B19V isolation ward, of which only two had positive throat swab samples. The other 15 patients and all HCWs tested negative for B19V. A total of 88 environmental surface and air samples were collected. Eight of the environmental samples collected in the B19V isolation ward before disinfection tested positive for B19V, while one sample tested positive after disinfection. In the general wards, all environmental samples collected before disinfection tested negative for B19V. All 24 samples collected from ambient air, whether in B19V isolation or general wards, before or after disinfection, tested negative for B19V. Conclusion: Existing methods of routine or terminal disinfection for air and object surfaces were effective in eliminating B19V from object surfaces and ambient air in the isolation and general wards. Material surfaces that are exposed to high frequency and easily contaminated by blood, body fluids, and indoor air were the focus of cleaning and disinfection. Nosocomial cross-infection of other immunocompromised patients and HCWs can be avoided if appropriate prevention and control measures are taken.

Molecular Characterization of Carbapenem-Resistant Acinetobacter baumannii Isolates Among Intensive Care Unit Patients and Environment.

Objective: Critical patients in intensive care unit (ICU) are highly susceptible to acquiring carbapenem-resistant Acinetobacter baumannii (CRAB) infection. To investigate the relationship between nosocomial infections and environmental health, we studied the distribution and homology of CRAB isolates from patients and environment and evaluated the effectiveness of infection control measures. Methods: In the 4-month study, we conducted a monthly CRAB screening of the ICU environment prior to disinfection in a Chinese teaching hospital. The ICU underwent routine disinfection procedures twice a day. We collected samples from the environment around the patients before disinfection. Clinical specimens from patients were also screened. The samples obtained were studied for phenotype and homology via antibiotic susceptibility testing, pulsed-field gel electrophoresis (PFGE), and whole-genome sequencing (WGS). Results: Ten specimens were sampled from ICU environments. Five were obtained in May 2020, and sputums from patient a in bed A at this time were cultured for CRAB isolates; in June 2020 another 5 environmental specimens were obtained from the same bed unit for CRAB, and sputums from patient b in bed A at this time were also cultured for CRAB isolates. Following intensive infection control measures, environmental sampling was negative in July and August. These 18 CRAB isolates all carried OXA-66 and OXA-23 genes and showed a similar resistance phenotype. WGS showed a close relationship among specimens from patients' sputum and their surroundings, but no homology between patients. Conclusion: The analysis of cgMLST and SNPs is more accurate for strain homology analysis. Our data confirm that CRAB isolates spread from patient to environment in ICU; however, contact isolation and disinfection measures are effective in avoiding transmission, highlighting the importance of continued education and surveillance of CRAB. WGS could provide rich information on antimicrobial resistance, which is of great value in scientific research and clinical diagnosis.

Bloodstream Infections Caused by Klebsiella pneumoniae Carbapenemase-Producing P. aeruginosa Sequence Type 463, Associated With High Mortality Rates in China: A Retrospective Cohort Study.

Objectives: Recently, KPC-producing P. aeruginosa has rapidly emerged and expanded in East China. Here we described the clinical impact and characteristics of bloodstream infections (BSIs) from the dominant KPC-producing CRPA belonging to Sequence Type (ST) 463. Methods: Retrospective cohort study was performed with CRPA BSI cases from 2019 to 2020 in a hospital in East China. Clinical characteristics, risk factors, and all-course mortality were evaluated. All CRPA isolates had whole-genome sequencing, antimicrobial susceptibility testing, and serum resistance assay. Representative isolates were tested for virulence in a Galleria mellonella infection model. Results: Among the 50 CRPA BSI cases, ST463 predominated (48.0%). In multivariate analysis, we found three independent risk factors for fatal outcome: KPC carriage (OR 4.8; CI95% 1.0-23.7; P = 0.05), Pitt bacteremia score (OR 1.3; CI95% 1.0-1.6; P = 0.02), and underlying hematological disease (OR 8.5; CI95% 1.6-46.4; P = 0.01). The baseline clinical variables were not statistically different across STs, however the 28-day mortality was significantly higher in ST463 cases than that in non-ST463 cases (66.7% vs 33.3%, P = 0.03). ExoU and exoS virulence genes coexisted in all ST463 isolates, and the carbapenem resistant gene blaKPC were produced in almost all ST463 isolates, significantly higher than in the non-ST463 group(95.8% vs 7.7%, P<0.001). ST463 CRPA isolates also showed higher resistance rates to antipseudomonal cephalosporins, monobactam, and fluoroquinolones. And ST463 CRPA was confirmed hypervirulence in the larvae model. The genome of one ST463 CRPA strain showed that the blaKPC-2 gene was the sole resistance gene located on a 41,104bp plasmid pZYPA01, carried on a 7-kb composite transposon-like element flanked by two IS26 elements (IS26-Tn3-tnpA-ISKpn27-blaKPC-2-ISKpn6-IS26). Plasmid from various species presented core blaKPC-2 was franked by mobile genetic element ISKpn27 and ISKpn6. Conclusions: In the ST463 CRPA BSI cohort, the mortality rates were higher than those in the non-ST463 CRPA BSI. The ST463 CRPA clone coharboring the blaKPC and exoU/exoS genes emerged and spread in East China, which might develop to a new threat in the clinic. Our results suggest that the surveillance of the new high-risk clone, ST463 CRPA, should be strengthened in China, even worldwide in the future.

A comparison of demographic, epidemiological and clinical characteristics of hospital influenza-related viral pneumonia patients.

BACKGROUND: Through the comparison of the demographic, epidemiological, and clinical characteristics of hospital human influenza (influenza A (H1N1) pdm09, H3N2, and B)-related and hospitalized avian-origin influenza A (H7N9)-related viral pneumonia patients, find the different between them. METHODS: A retrospective study was conducted in hospitalized influenza-related viral pneumonia patients. RESULTS: Human influenza A-related patients in the 35-49-year-old group were more than those with B pneumonia patients (p = 0.027), and relatively less in the ≥ 65-year-old group than B pneumonia patients (p = 0.079). The proportion of comorbid condition to human influenza A pneumonia was 58%, lower than B pneumonia and H7N9 pneumonia patients (78% vs. 77.8%; p = 0.013). The proportion of invasive mechanical ventilation (IMV), lymphocytopenia, elevated lactate dehydrogenase to hospitalized human influenza A-related viral pneumonia patients was higher than B pneumonia patients (p < 0.05), but lower than H7N9 pneumonia patients (p < 0.05). In the multivariate analysis, pulmonary consolidation (odds ratio (OR): 13.67; 95% confidence interval (CI) 1.54-121.12; p = 0.019) and positive bacterial culture (sputum) (OR: 7.71; 95% CI 2.48-24.03; p < 0.001) were independently associated with IMV, while shock (OR: 13.16; 95% CI 2.06-84.07; p = 0.006), white blood cell count > 10,000/mm3 (OR: 7.22; 95% CI 1.47-35.58; p = 0.015) and positive bacterial culture(blood or sputum) (OR: 6.27; 95% CI 1.36-28.85; p = 0.018) were independently associated with death in the three types hospitalized influenza-related viral pneumonia patients. CONCLUSIONS: Hospital influenza B-related viral pneumonia mainly affects the elderly and people with underlying diseases, while human influenza A pneumonia mainly affects the young adults; however, the mortality was similar. The hospitalized human influenza A-related viral pneumonia patients was severer than B pneumonia patients, but milder than H7N9 pneumonia patients. Pulmonary consolidation and positive bacterial culture (sputum) were independently associated with IMV, while shock, white blood cell count > 10,000/mm3, and positive bacterial culture (blood or sputum) were independently associated with death to three types hospitalized influenza-related viral pneumonia patients.

SARS-CoV-2 RNA detection of hospital isolation wards hygiene monitoring during the Coronavirus Disease 2019 outbreak in a Chinese hospital.

OBJECTIVES: The aim of this paper was to monitor the presence of SARS-Cov-2 among hospital environment surfaces, sewage, and personal protective equipment (PPE) of staffs in isolation wards in the First Affiliated Hospital of Zhejiang University, China. METHODS: Surfaces of objects were routinely wiped with 1000mg/L chlorine containing disinfectant. Air and sewage disinfection was proceeded routinely and strictly. Hospital environmental surfaces and PPE of staffs in isolation wards were sampled using swabs. The sewage from various inlet and outlets were sampled. The respiratory and stool specimens of patients were collected. The respiratory specimens of staffs in the isolation wards were also sampled once a week. Quantitative real-time reverse transcription PCR (qRT-PCR) methods were used to confirm the existence of SARS-Cov-2 RNA. Viral culture was done for the samples positive for SARS-Cov-2 RNA. RESULTS: During the study period, 33 laboratory-confirmed patients were hospitalized in isolation wards in the hospital. None of SARS-Cov-2 RNA was detected among the 36 objects surface samples and 9 staffs PPE samples in isolation wards. Though the 3 sewage samples from the inlet of preprocessing disinfection pool were positive for SARS-CoV-2 RNA and the sample from the outlet of preprocessing disinfection pool was weakly positive, the sewage sample from the outlet of the last disinfection pool was negative. All of the 5 sewage samples from various points were negative by viral culture of SARS-Cov-2. None of the respiratory specimens of staffs in the isolation wards were positive. CONCLUSIONS: Though SARS-Cov-2 RNA of the sewage samples were positive from inlets of the sewage disinfection pool and negative from the outlet of the last sewage disinfection pool, no viable virus was detected by culture. The monitoring data in this study suggested that the strict disinfection and hand hygiene could decrease the hospital-associated COVID-19 infection risk of the staffs in isolation wards.

Dual-functionalized liposome by co-delivery of paclitaxel with sorafenib for synergistic antitumor efficacy and reversion of multidrug resistance.

Multidrug resistance (MDR) remains one of the major reasons for inefficiency of many chemotherapeutic agents in cancer therapy. In this study, a D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and polylysine-deoxycholic acid copolymer (PLL-DA) co-modified cationic liposome coating with hyaluronic acid (HA) was constructed for co-delivery of paclitaxel (PTX) and chemosensitizing agent, sorafenib (SOR) to treat the MDR cancer. The multifunctional liposome (HA-TPD-CL-PTX/SOR) presented good stability against rat plasma and was capable of reversing surface zeta potential under acidic conditions in the presence of HAase. Additionally, experimental result confirmed that the PLL-DA copolymer would facilitate the endo-lysosomal escape of the liposome. In vitro study demonstrated that HA-TPD-CL-PTX/SOR could significantly enhance drug accumulation in resistant MCF-7/MDR cells by inhibiting the P-gp efflux, and effectively inhibited growth of tumor cells. Furthermore, the liposome showed an enhanced anticancer activity in vivo, with a tumor growth inhibition rate of 78.52%. In summary, HA-TPD-CL-PTX/SOR exhibited a great potential for effective therapy of resistant cancers by combining with chemotherapeutic agents and could be a promising nano-carrier for reversing MDR and improving the effectiveness of chemotherapy.