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.

Hemophagocytic Lymphohistiocytosis Secondary to Disseminated Histoplasmosis in HIV Seronegative Patients: A Case Report and Review of the Literature.

Hemophagocytic lymphohistiocytosis (HLH) secondary to Histoplasma capsulatum infection is a rare disorder with poor outcome. Although cases of patients with human immunodeficiency virus (HIV) infection have been well documented, little study has reported in the setting of HIV seronegative. In this study, we report a case of HLH secondary to histoplasmosis in an immunocompetent patient in China and review all cases on this situation. The objective was to summary their epidemiology, clinical characteristics, diagnostic approaches, and therapeutic response. A 46-year-old male cooker presented fever, fatigue, anorexia, and weight loss. Bone marrow examination suggest fungus organism and hemophagocytosis, and further, bone marrow culture confirmed Histoplasma capsulatum, as the etiology of HLH. The patient was successfully treated. We reviewed a total of the 13 cases (including our patient) of HLH with histoplasmosis in intact immunology patients. Twelve of the 13 patients are from endemic areas, and nine of the 12 cases are from emerging endemic areas, India and China. Three patients had sojourn history may related to the disease onset. Twelve of the 13 cases fulfilled HLH-2004 criteria. The diagnosis of Histoplasma capsulatum infection was established by histological examination (13 of 13), culture (4 of 13), molecular method (2 of 13), and antigen or serological assays (2 of 13). Amphotericin B, posaconazole, and itraconazole show favorable activity against the fungus, seven patients used specific treatment for HLH. For analysis of outcomes, two of the 13 patients died. Our present case report and literature review show that disseminated Histoplasma capsulatum infection with HLH in the immunocompetent population becomes increasingly common in emerging endemic areas and have high mortality. It is necessary for clinicians to improve the awareness of disease diagnosis due to the atypical population and disease presentation. Timely diagnosis and early use of antifungal agents will lead to favorable prognosis.

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.

Clinical Characteristics and Risk Factors for Bloodstream Infection Due to Carbapenem-Resistant Klebsiella pneumoniae in Patients with Hematologic Malignancies.

PURPOSE: The aim was to examine the clinical characteristics and risk factors for bloodstream infection (BSI) due to carbapenem-resistant Klebsiella pneumoniae (CRKP) in patients with hematologic malignancies. MATERIALS AND METHODS: A single-centre, retrospective case-control study representing 734 patients with hematologic malignancies between January 1, 2017, and December 31, 2018, was conducted. Demographic and clinical data were collected from the hospital electronic medical records system. RESULTS: Among the 734 patients with hematologic malignancies, 3% (22/734) of the patients developed CRKP BSI during their hospitalization. Overall 28-day all-cause mortality reached 77.3% (17/22). Patients with Pitt bacteremia score (PBS) >4, pneumonia and septic shock were more frequent in the non-survivors versus the survivors. Compared with the non-survivors in antimicrobial treatment, combination therapy of tigecycline and polymyxin B was more common in the survivors. The independent risk factors associated with CRKP BSI were CRKP rectal colonization (OR, 11.067; CI=4.43-27.644; P<0.001; 3 points), severe neutropenia (OR, 4.095; CI=0.876-19.141; P=0.073; 1 point) and invasive mechanical ventilation (IMV) within the previous 30 days to onset of BSI (OR, 18.444; CI=1.787-190.343; P=0.014; 4 points). The total risk score of ≥5 indicated that the probability of CRKP BSI occurrence was above 48%. CONCLUSION: CRKP BSI in patients with hematologic malignancies is associated with high mortality. The risk factor-based prediction model might help clinicians to start prompt effective anti-infective therapy in patients with suspicion of CRKP BSI and improve outcomes.

Clinical and Microbiological Characteristics of Community-Onset Carbapenem-Resistant Enterobacteriaceae Isolates.

OBJECTIVE: The aim of this study was to investigate the clinical and microbiological features of community-onset CRE (CO-CRE) obtained from outpatients at a tertiary hospital in China. PATIENTS AND METHODS: We isolated 64 CRE strains from outpatients and divided them into three groups: 36 hospital-acquired CRE (HA-CRE), 28 CO-CRE including 15 community-acquired CRE (CA-CRE) and 13 healthcare-associated CRE (HCA-CRE). Clinical information was collected. The antibiotic susceptibilities of the 28 CO-CRE strains were tested. Whole-genome sequencing (WGS) was conducted, and then drug resistance gene analysis was performed. CgMLST and SNP comparisons were used to analyze the genomic relationship with E. coli and K. pneumoniae strains, respectively. RESULTS: In this study, the 28 CO-CRE isolates included K. pneumoniae (53.6%), E. coli (28.6%), E. cloacae (7.1%), C. freundii (7.1%) and E. asburiae (3.6%). The CO-CRE isolates were mainly isolated from urine samples (75%). The ceftazidime/avibactam resistance rate of community-onset E. coli was significantly higher than that of community-onset K. pneumoniae, while the aztreonam, ciprofloxacin, levofloxacin, and chloramphenicol resistance rates were significantly lower (P<0.05). Thirteen of the 15 K. pneumoniae strains belonged to ST11 containing blaKPC-2. Correspondingly, 8 E. coli strains belonged to 7 STs, and they all were NDM producers. K. pneumoniae belonged to two major clusters, while E. coli was sporadic. The number of SNPs separating ST11 K. pneumoniae isolates ranged from 7 to 2154. CONCLUSION: Community-onset CRE is not rare, and the dissemination of E. coli was sporadic while K. pneumoniae was clonal spread with similar STs as HA-CRE. Active surveillance of CRE in the community setting is in demand.

Importance of fibrosis 4 index score and mode of anti-fungal treatment to the outcome of Cryptococcal meningitis in hepatitis B virus-infected patients.

BACKGROUND: Hepatitis B virus (HBV) and the associated cirrhosis are risk factors for cryptococcal meningitis (CM). However, the clinical features of co-infection with HBV and CM are unclear. METHODS: Seventy-nine HBV-infected CM patients and 79 HBV-uninfected CM patients were enrolled in a case-control matching study from 476 CM patients. Fibrosis 4 index (FIB4) was used for assessment of HBV-related fibrosis/cirrhosis. Demographic characteristics, symptoms, routine blood tests, liver function and cerebrospinal fluid (CSF) profiles were compared between the two groups. Kaplan-Meier analysis and Cox proportional hazards model were used to assess factors associated with 10-week mortality. RESULTS: Male gender was associated with HBV-infected CM patients (p = .006). CM patients with HBV experienced similar frequencies of symptoms but had lower white blood cell (WBC) (p < .001), platelet (p < .001) and albumin (p = .012), and increased aspartate amino transaminase (AST) (p = .009) and total bilirubin (TBIL) levels (p < .001). Patients with and without HBV infection had similar 10-week cumulative survival rates (85.9 ± 4.2% vs. 78.6 ± 5.4%, p = .569). The hazard ratio was 3.7 times higher for those with FIB4 ≥ 3.25 (p = .020) and 4.5 times higher for those with HBV infection not treated with Amphotericin B + flucytosine ± fluconazole (p = .023). CONCLUSION: HBV-infected CM population experience lower WBC, platelet and albumin, and higher AST and TBIL. Ten-week survival rate was similar between HBV-infected and HBV-uninfected CM patients. CM patients with high FIB4 or not treated with Amphotericin B + flucytosine ± fluconazole are at a higher risk of death.