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Lixia Li,1,* Xiaohui Huang,1,* Jingxian Liu,2,* Chao Li,1 Zhiyan Lin,1 Rongrong Ren,3 Yan Zhang,3 Haoshu Ding,3 Jihui Chen,1 Yanfei Mao3 1Department of Pharmacy, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Clinical Laboratory, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Anesthesiology and SICU, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yanfei Mao; Jihui Chen, Email maoyanfei@xinhuamed.com.cn; chenjihui@xinhuamed.com.cnBackground: Polymyxin B (PMB)-based combination therapies are used to treat severe carbapenem-resistant gram-negative bacterial (CR-GNB) infections. This observational study investigated the relationship between clinical factors, including PMB concentration, and clinical efficacy and safety.Patients and Methods: Polymyxin B regimens were optimized through therapeutic drug monitoring (TDM) and area under the concentration-time curve (AUC). In all, 382 samples were tested from 130 patients. Logistic regression was used to analyze the relationships between variables with clinical efficacy and 30-day mortality factors were analyzed by Cox regression. The sensitivity and specificity of Cmin and AUC for the occurrence of acute kidney injury (AKI) were determined by ROC curve analysis.Results: The clinical effectiveness of PMB was 65.4%. Multivariate logistic regression analysis revealed that lung infection, continuous renal replacement therapy, and C-reactive protein were independent factors significantly associated with efficacy. AKI occurred in 14.6% of the patients during treatment; age > 73 years (OR: 3.63; 95% CI: 1.035– 12.727; P = 0.044), Cmin greater than 2.3 μg/mL (OR: 7.37; 95% CI: 1.571– 34.580; P = 0.011), combined vancomycin (OR: 9.47; 95% CI: 1.732– 51.731; P = 0.009), and combined piperacillin-tazobactam (OR: 21.87; 95% CI: 3.139– 152.324; P = 0.002) were independent risk factors. The identified PMB cut-offs for predicting AKI were Cmin = 2.3 μg/mL and AUC = 82.0 mg h/L.Conclusion: Polymyxin B-based combination regimens are effective in treating CR-GNB infections, particularly bloodstream infections, but have shown unsatisfactory for lung infections. Cmin ≥ 2.3 μg /mL and AUC ≥ 82.0 mg h/L may increase PMB-associated AKI incidence. PMB dose should be adjusted based on TDM to ensure efficacy.Keywords: Polymyxin B, PMB therapeutic drug monitoring, TDM, carbapenem-resistant gram-negative bacteria, CR-GNB, clinical efficacy, acute kidney injury, AKI

Abstract This study aimed to investigate the epidemiological characteristics and trends over time of carbapenemase-producing (e.g., KPC, NDM, VIM, IMP, and OXA-48) Gram-negative bacteria (CPGNB). Non-duplicated multi-drug resistant Gram-negative bacteria (MDRGNB) were collected from the First Affiliated Hospital of Zhengzhou University from April 2019 to February 2023. Species identification of each isolate was performed using the Vitek2 system and confirmed by matrix-assisted laser desorption ionization-time of flight mass spectrometry according to the manufacturer's instructions. PCR detected carbapenem resistance genes in the strains, strains carrying carbapenem resistance genes were categorized as CPGNB strains after validation by carbapenem inactivation assay. A total of 5705 non-repetitive MDRGNB isolates belonging to 78 different species were collected during the study period, of which 1918 CPGNB were validated, with the respiratory tract being the primary source of specimens. Epidemiologic statistics showed a significant predominance of ICU-sourced strains compared to other departments. Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa were the significant CPGNB in Henan, and KPC and NDM were the predominant carbapenemases. Carbapenem-resistant infections in Henan Province showed an overall increasing trend, and the carriage of carbapenemase genes by CPGNB has become increasingly prevalent and complicated. The growing prevalence of CPGNB in the post-pandemic era poses a significant challenge to public safety.

Background/purpose(s): The continuously increasing carbapenem resistance within Enterobacterales and Pseudomonas poses a threat to public health, nevertheless, the molecular characteristics of which in southern China still remain limited. And carbapenemase identification is a key factor in effective early therapy of carbapenem-resistant bacteria infections. We aimed to determine the molecular characteristics of these pathogens and compare commercial combined disc tests (CDTs) with the modified carbapenem inactivation method (mCIM) and EDTA-CIM (eCIM) in detecting and distinguishing carbapenemases using whole genome sequencing (WGS). Methods: A total of 78 Enterobacterales, 30 Pseudomonas were obtained from two tertiary hospitals in southern China. Susceptibility tests were conducted using an automated VITEK2 compact system with confirmation via the Kirby-Bauer method. The WGS was conducted on all clinical isolates and the molecular characteristics were analyzed by screening the whole genome sequences. CDTs with or without cloxacillin, mCIM, and eCIM, were performed and compared by taking WGS results as the benchmark. Results: A total of 103 carbapenem non-susceptible and 5 carbapenem susceptible bacteria were determined, with Klebsiella pneumoniae (42.7%), Pseudomonas aeruginosa (23.3%) and Escherichia coli (18.4%) being most prevalent. Carbapenemase genes were detected in 58 (56.3%) of the 103 carbapenem-non-susceptible clinical isolates, including 46 NDM, 6 KPC, 3 IMP, 1 IPM+VIM, 1NDM+KPC, and 1 OXA-181. Carbapenemase-producing isolates were detected more frequently in Enterobacterales (76.3%). Among K. pneumoniae, the major sequence types were st307 and st11, while among E. coli and P. aeruginosa, the most prevalent ones were st410 and st242 respectively. For carbapenemase detection in Enterobacterales, the mCIM method achieved 100.00% (95% CI, 92.13-100.00%) sensitivity and 94.44% (70.63-99.71%) specificity (kappa, 0.96); for Pseudomonas, detection sensitivity was 100% (5.46-100.00%), and 100% (84.50-100.00%) specificity (kappa, 0.65). Commercial CDT carbapenemase detection sensitivity for Enterobacterales was 96.49% (86.84-99.39%), and 95.24% (74.13-99.75%) specificity (kappa, 0.90); for Pseudomonas, carbapenemase detection sensitivity was 100.00% (5.46-100.00%) and 37.93% (21.30-57.64%) specificity (kappa, 0.04). When cloxacillin testing was added, CDT specificity reached 84.61% (64.27-94.95%). Conclusion: The molecular epidemiology of carbapenem-non-susceptible isolates from pediatric patients in Southern China exhibited distinctive characteristics. Both the mCIM-eCIM combination and CDT methods effectively detected and differentiated carbapenemases among Enterobacterales isolates, and the former performed better than CDT among Pseudomonas. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to compare the efficacy and safety of colistin sulfate (CS) with polymyxin B sulfate (PMB) in the treatment of pneumonia induced by carbapenem-resistant Gram-negative bacteria (CR-GNB). Methodology: Patients diagnosed with pneumonia caused by CR-GNB and admitted to the intensive care unit (ICU) from January 2020 to September 2022 were enrolled in this study. The patients were divided into the CS group and the PMB group according to their medication regimens. Group-wise demographic data, clinical efficacy, prognosis, and adverse events were analyzed and compared. Results: A total of 120 patients (68 in the CS group and 52 in the PMB group) with pneumonia were included in the study. The majority of the pathogens were CR-Acinetobacter baumannii, followed by CR-Klebsiella pneumoniae, and CR-Pseudomonas aeruginosa. The clinical response rates in the CS and PMB groups after treatment were 62.0% and 65.4%, bacterial clearances were 44.0% and 36.5%, 28-day mortality rates were 16.0% and 13.5%, respectively; no significant differences between the two treatments were found. Nevertheless, the adverse effects were significantly less common in the CS group than in the PMB group, especially when treatments were administered intravenously. Conclusions: CS, a novel polymyxin E formulation, is as effective as PMB in treating pneumonia induced by CR-GNB while causing less side effects. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the epidemiological characteristics and trends over time of carbapenemase-producing (e.g., KPC, NDM, VIM, IMP, and OXA-48) Gram-negative bacteria (CPGNB). Non-duplicated multi-drug resistant Gram-negative bacteria (MDRGNB) were collected from the First Affiliated Hospital of Zhengzhou University from April 2019 to February 2023. Species identification of each isolate was performed using the Vitek2 system and confirmed by matrix-assisted laser desorption ionization-time of flight mass spectrometry according to the manufacturer's instructions. PCR detected carbapenem resistance genes in the strains, strains carrying carbapenem resistance genes were categorized as CPGNB strains after validation by carbapenem inactivation assay. A total of 5705 non-repetitive MDRGNB isolates belonging to 78 different species were collected during the study period, of which 1918 CPGNB were validated, with the respiratory tract being the primary source of specimens. Epidemiologic statistics showed a significant predominance of ICU-sourced strains compared to other departments. Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa were the significant CPGNB in Henan, and KPC and NDM were the predominant carbapenemases. Carbapenem-resistant infections in Henan Province showed an overall increasing trend, and the carriage of carbapenemase genes by CPGNB has become increasingly prevalent and complicated. The growing prevalence of CPGNB in the post-pandemic era poses a significant challenge to public safety. [ABSTRACT FROM AUTHOR]

Abstract Background Carbapenem-resistant Gram-negative bacteria (CR-GNB) are a critical public health threat globally; however, there are inadequate surveillance data, especially in intensive care units (ICU), to inform infection prevention and control in many resource-constrained settings. Here, we assessed the prevalence of CR-GNB infections and risk factors for acquisition in a Kenyan ICU. Methods A hospital-based cross-sectional study design was adopted, recruiting 162 patients clinically presenting with bacterial infection after 48 h of ICU admission, from January to October 2022 at the Nairobi West Hospital, Kenya. Demographics and clinical data were collected by case report form. The type of sample collected, including blood, tracheal aspirate, ascitic tap, urine, stool, and sputum depended on the patient’s clinical presentation and were transported to the hospital Microbiology laboratory in a cool box for processing within 2 h. The samples were analyzed by cultured and BD Phoenix system used for isolates’ identity and antimicrobial susceptibility. Results CR-GNB infections prevalence was 25.9% (42/162), with Klebsiella pneumoniae (35.7%, 15/42) and Pseudomonas aeruginosa (26.2%, 11/42) predominating. All isolates were multidrug-resistant (MDR). P. aeruginosa and A. baumannii were 100% colistin-resistant, while K. pneumoniae (33.3%) was tigecycline-resistant. History of antibiotics (aOR = 3.40, p = 0.005) and nasogastric tube (NGT) use (aOR = 5.84, p =

Abstract Background Predicting whether Carbapenem-Resistant Gram-Negative Bacterial (CRGNB) cause bloodstream infection when giving advice may guide the use of antibiotics because it takes 2–5 days conventionally to return the results from doctor's order. Methods It is a regional multi-center retrospective study in which patients with suspected bloodstream infections were divided into a positive and negative culture group. According to the positive results, patients were divided into the CRGNB group and other groups. We used the machine learning algorithm to predict whether the blood culture was positive and whether the pathogen was CRGNB once giving the order of blood culture. Results There were 952 patients with positive blood cultures, 418 patients in the CRGNB group, 534 in the non-CRGNB group, and 1422 with negative blood cultures. Mechanical ventilation, invasive catheterization, and carbapenem use history were the main high-risk factors for CRGNB bloodstream infection. The random forest model has the best prediction ability, with AUROC being 0.86, followed by the XGBoost prediction model in bloodstream infection prediction. In the CRGNB prediction model analysis, the SVM and random forest model have higher area under the receiver operating characteristic curves, which are 0.88 and 0.87, respectively. Conclusions The machine learning algorithm can accurately predict the occurrence of ICU-acquired bloodstream infection and identify whether CRGNB causes it once giving the order of blood culture.

Keyang Li,1,* Debao Li,2,* Hongliang Dong,1 Dongmei Ren,2 Dandan Gong,1 Shubo Wang,1 Yang Li,1 Yuanyuan Wu,1 Jikang Yang,3 Wenjuan Yan,4 Yi Li4 1Department of Clinical Pharmacy, Jiaozuo People’s Hospital, Jiaozuo, Henan, People’s Republic of China; 2Department of Clinical Laboratory, Jiaozuo People’s Hospital, Jiaozuo, Henan, People’s Republic of China; 3Infectious Diseases Department, Jiaozuo People’s Hospital, Jiaozuo, Henan, People’s Republic of China; 4Department of Clinical Laboratory, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenjuan Yan; Yi Li, Department of Clinical Laboratory, Henan Provincial People’s Hospital, Weiwu Road 7#, Jinshui District, Zhengzhou, Henan, 450003, People’s Republic of China, Tel +86 15225061830 ; +86 15939039006, Email yanwenjuan2008@126.com; liyilabmed@henu.edu.cnPurpose: Since the introduction of ceftazidime–avibactam (CZA) in the Chinese market, accumulating clinical evidence has substantiated its efficacy in the treatment of infections caused by carbapenem-resistant gram-negative bacteria (CR-GNB). Nevertheless, an ongoing debate persists concerning the choice between monotherapy and combination therapy when devising clinical anti-infection protocols.Patients and Methods: This retrospective, single-center observational study enrolled patients with CR-GNB infections who received CZA treatment between December 2019 and August 2023. The primary outcome assessed was 30-day mortality, and the secondary outcome measured was 14-day bacterial clearance. A multivariate Cox regression model was used to identify variables that were independently associated with 30-day mortality rate.Results: Eighty-three patients were enrolled in the study; of which, 45 received CZA monotherapy, whereas 38 received combination therapy. The overall 30-day mortality rate was 31.3%, and no significant difference was observed in the 30-day mortality rates between the CZA combination therapy and monotherapy groups (31.6% vs 31.1%, p=0.963). After adjustment by propensity score matching, the 30-day mortality rate was not significantly different between the two groups (28.6% vs 31.4%, p=0.794). Multivariate COX analysis revealed that age and SOFA score were independent predictors of 30-day mortality.Conclusion: Combination therapy with CZA and other antimicrobials was not found to have an advantage over monotherapy in reducing the 30-day mortality rate.Keywords: ceftazidime-avibactam, carbapenem-resistant gram-negative bacteria, combination therapy K. pneumoniae carbapenemase

Background: Predicting whether Carbapenem-Resistant Gram-Negative Bacterial (CRGNB) cause bloodstream infection when giving advice may guide the use of antibiotics because it takes 2–5 days conventionally to return the results from doctor's order. Methods: It is a regional multi-center retrospective study in which patients with suspected bloodstream infections were divided into a positive and negative culture group. According to the positive results, patients were divided into the CRGNB group and other groups. We used the machine learning algorithm to predict whether the blood culture was positive and whether the pathogen was CRGNB once giving the order of blood culture. Results: There were 952 patients with positive blood cultures, 418 patients in the CRGNB group, 534 in the non-CRGNB group, and 1422 with negative blood cultures. Mechanical ventilation, invasive catheterization, and carbapenem use history were the main high-risk factors for CRGNB bloodstream infection. The random forest model has the best prediction ability, with AUROC being 0.86, followed by the XGBoost prediction model in bloodstream infection prediction. In the CRGNB prediction model analysis, the SVM and random forest model have higher area under the receiver operating characteristic curves, which are 0.88 and 0.87, respectively. Conclusions: The machine learning algorithm can accurately predict the occurrence of ICU-acquired bloodstream infection and identify whether CRGNB causes it once giving the order of blood culture. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the rationality of clinical application of colistin sulfate for injection in the hospital, so as to provide reference for promoting the rational application in clinic. METHODS: General information, infection site, etiological examination results, usage and dosage, drug combination and course of treatment of patients with colistin sulfate for injection in the hospital from Dec. 2020 to Mar. 2023 were retrospectively collected. Rationality of clinical application of colistin sulfate for injection was analyzed by referring to drug instructions, guidelines, consensus and related literature. RESULTS: A total of 113 patients treated with colistin sulfate for injection were included, of which 24 patients (21. 2%) had no indication of medication. And 15 patients (13. 3%) were given a loading dose. The majority of patients (101 cases, 89. 4%) received the minimum intravenous daily dose of 1 million U. Totally 43 patients (38. 1%) were combined with aerosol inhalation and the aerosol inhalation dose was too low in one patient (0. 9%). Twenty-seven patients (23. 9%) received monotherapy and 4 patients (3. 5%) did not meet guidelines or consensus recommendations. The treatment course was too short in 19 patients(16. 8%) and too long in 8 patients (7. 1%). There were some problems in the clinical application of colistin sulfate for injection in our hospital, such as incomplete medication indication, too small dosage of aerosol inhalation, no drug combination and improper treatment course. CONCLUSIONS: The application of colistin sulfate for injection in the hospital needs to be further standardized, and in-depth research on pharmacokinetics/ pharmacodynamics and clinical application is urgently needed, so as to optimize the usage and dosage of colistin sulfate for injection, and improve the application rationality and treatment outcome. [ABSTRACT FROM AUTHOR]

Background and purpose: The production of metallo‐β‐lactamases is a major mechanisms adopted by bacterial pathogens to resist carbapenems. Repurposing approved drugs to restore the efficacy of carbapenems represents an efficient and cost‐effective approach to fight infections caused by carbapenem resistant pathogens. Experimental approach: The nitrocefin hydrolysis assay was employed to screen potential New Delhi metallo‐lactamase‐1 (NDM‐1) inhibitors from a commercially available U.S. Food and Drug Administration (FDA) approved drug library. The mechanism of inhibition was clarified by metal restoration, inductively coupled plasma mass spectrometry (ICP‐MS) and molecular dynamics simulation. The in vitro synergistic antibacterial effect of the identified inhibitors with meropenem was determined by the checkerboard minimum inhibitory concentration (MIC) assay, time‐dependent killing assay and combined disc test. Three mouse infection models were used to further evaluate the in vivo therapeutic efficacy of combined therapy. Key results: Twelve FDA‐approved compounds were initially screened to inhibit the ability of NDM‐1 to hydrolyse nitrocefin. Among these compounds, dexrazoxane, embelin, candesartan cilexetil and nordihydroguaiaretic acid were demonstrated to inhibit all tested metallo‐β‐lactamases and showed an in vitro synergistic bactericidal effect with meropenem against metallo‐β‐lactamases‐producing bacteria. Dexrazoxane, embelin and candesartan cilexetil are metal ion chelating agents, while the inhibition of NDM‐1 by nordihydroguaiaretic acid involves its direct binding to the active region of NDM‐1. Furthermore, these four drugs dramatically rescued the treatment efficacy of meropenem in three infection models. Conclusions and implications: Our observations indicated that dexrazoxane, embelin, candesartan cilexetil and nordihydroguaiaretic acid are promising carbapenem adjuvants against metallo‐β‐lactamases‐positive carbapenem resistant bacterial pathogens. [ABSTRACT FROM AUTHOR]

The current situation of multidrug-resistant bacteria infection in surgical patients is becoming increasingly severe. Effective prevention of cross transmission of multidrug-resistant bacteria and common site infections in ICU patients is the key step. In response to the key issues in the prevention and control of multidrug-resistant bacteria infection, a comprehensive strategy is implemented. Core measures such as early recognition, preemptive isolation, active screening, and graded prevention and control are taken for patients, and targeted preventive measures for common infection sites are combined to form a detection and control system of multidrug-resistant bacteria for ICU patients. By moving forward and extrapolating to the general ward, the prevention and control system effectively reduced the incidence of multidrug-resistant bacteria colonization/infection in surgical patients.

Jiaxin Yu,1,2 Wei Zuo,1,2 Hongwei Fan,1,3 Jiayu Wu,1,2 Luyao Qiao,1,2,4 Benyu Yang,1,2,5 Wenxi Li,1,2,5 Yang Yang,1,2,&ast; Bo Zhang1,2,&ast; 1Department of Pharmacy, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 2State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 3Department of Infectious Medicine, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 4Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 5School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Yang; Bo Zhang, Department of pharmacy, Peking Union Medical College Hospital, Dongdan Campus, No. 1 Shuaifuyuan Wangfujing Dongcheng, District, Beijing, 100730, People’s Republic of China, Tel/Fax +86 10 69156527, Email yangyangsdu2010@126.com; zhangbopumch@163.comPurpose: Ceftazidime-avibactam (C-A) is a treatment option for carbapenem-resistant gram-negative bacterial (CR-GNB) infections, but little is known regarding its suitability for the intensive care unit (ICU). The current study aimed to analyze use of C-A for critically ill patients, determine independent predictors of clinical outcome and mortality and explore routine dosages for patients in continuous renal replacement therapy (CRRT).Patients and Methods: A single-center, retrospective and observational study was conducted in critically ill patients receiving different C-A-based therapies for CR-GNB infections in a tertiary teaching hospital in Beijing, China. Demographic data, severity of infection, clinical outcomes and mortality were assessed. The primary and secondary outcome of this study was 90-day all-cause mortality and 14-day clinical response, respectively.Results: A total of 43 patients with CR-GNB infection were enrolled, including 14 (32.6%) patients received C-A monotherapy. C-A monotherapy and combination with other agents did not affect 14-day clinical response or 90-day survival. All-cause mortality at 90-days was 39.5% (17/43). Multivariate Cox analysis showed that concomitant with bloodstream infection was independent risk factors for 90-day mortality and that the time to initiation of C-A and Acute Physiology and Chronic Health Evaluation (APACHE) score was independent predictors of 14-day clinical response. Five CRRT patients who received high-dose C-A therapy (> 3.75 g/d) had prolonged survival compared with 5 who received low-dose C-A (< 3.75 g/d, p = 0.03).Conclusion: C-A was an effective therapy for severe CR-GNB infections and clinical response correlated with the time of C-A initiation. A dosage > 3.75g/d C-A was associated with prolonged survival of CRRT patients. Randomized controlled trials or multicenter studies are needed to confirm these findings.Keywords: ceftazidime-avibactam, renal replacement therapy, infections, intensive care unit, carbapenem-resistant gram-negative bacteria

Abstract Background The appropriate administration regimen of polymyxin B is yet controversial. The present study aimed to explore the optimal dose of polymyxin B under therapeutic drug monitoring (TDM) guidance. Methods In China’s Henan province, 26 hospitals participated in a randomized controlled trial. We included patients with sepsis caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) susceptible to polymyxin B. The patients were randomly divided into a high-dose (HD) group or a low-dose (LD) group and received 150 mg loading dose, 75 mg every 12 h and 100 mg loading dose, 50 mg every 12 h, respectively. TDM was employed to determine if the dose of polymyxin B needs adjustment based on the area under the concentration–time curve across 24 h at a steady state (ssAUC0–24) of 50–100 mg h/L. The primary outcome was the 14-day clinical response, and the secondary outcomes included 28- and 14-day mortality. Results This trial included 311 patients, with 152 assigned to the HD group and 159 assigned to the LD group. Intention-to-treat analysis showed that the 14-day clinical response was non-significant (p = 0.527): 95/152 (62.5%) in the HD group and 95/159 (59.7%) in the LD group. Kaplan–Meier’s 180-day survival curve showed survival advantage in the HD group than in the LD group (p = 0.037). More patients achieved the target ssAUC0–24 in the HD than in the LD group (63.8% vs. 38.9%; p = 0.005) and in the septic shock subgroup compared to all subjects (HD group: 71.4% vs. 63.8%, p = 0.037; LD group: 58.3% vs. 38.9%, p = 0.0005). Also, the target AUC compliance was not correlated with clinical outcomes but with acute kidney injury (AKI) (p = 0.019). Adverse events did not differ between the HD and LD groups. Conclusion A fixed polymyxin B loading dose of 150 mg and a maintenance dose of 75 mg every 12 h was safe for patients with sepsis caused by CR-GNB and improves long-term survival. The increased AUC was associated with increased incidence of AKI, and TDM results were valued to prevent AKI. Trial registration Trial registration ClinicalTrials.gov: ChiCTR2100043208, Registration date: January 26, 2021.

Objectives: Limited data on clinical and microbiological efficacy, patient mortality, and other associated factors are available for ceftazidime/avibactam (CAZ/AVI)-based regimens for carbapenem-resistant Gram-negative bacteria (CR-GNB). This study aimed to assess these issues retrospectively using multicenter data. Methods: This multicenter study included CR-GNB infected patients treated with CAZ/AVI-based regimens for more than three days. Patient characteristics, bacterial culture reports, drug-sensitivity test results, and antibiotic use, including CAZ/AVI use, were extracted from the patient's clinical records. The clinical and microbiological efficacy of the combined drug regimen and patient mortality were evaluated according to corresponding definitions. Univariate and multivariate logistic regressions were performed to explore the efficacy and mortality-related factors. Results: A total of 183 patients with CR-GNB infection were considered for the analysis according to the inclusion and exclusion criteria. After the treatment of CAZ/AVI-based regimens, the clinical efficacy was 75.4 %. The 7-day microbial efficacy and clearance rate after treatment were 43.7 % and 66.0 %, respectively. Moreover, 30-day all-cause and in-hospital mortality were 11.5 % and 14.2 %, respectively. Harboring renal dysfunction (creatinine clearance rate (CCR) of

Background: Carbapenem-resistant gram-negative bacterial (CRGNB) infections are increasing among kidney transplant recipients, and effective therapeutic options are limited. This study aimed to investigate the efficacy and adverse events associated with combination therapy tigecycline in renal transplant patients with CRGNB infections. Methods: This study retrospectively analyzed 40 Chinese patients with confirmed or suspected CRGNB infections who received tigecycline therapy. The patients' case features and clinical and microbiological data were analyzed. Results: A total of 40 renal transplant recipients received tigecycline therapy for a median duration of 9 (range, 3-25) days. CRGNB isolates were obtained from the organ preservation solution of the donor kidney in 28 patients, with confirmed transmission in 4 patients. Infections were detected in the bloodstream, urinary tract, sputum, and wound. The most prevalent isolates were Klebsiella pneumoniae (75%, 30/40), Acinetobacter baumannii (15%, 6/40), and Escherichia coli (10%, 4/40). A clinical response was observed in 32 (80%) patients. The 28-day all-cause mortality rate was 7.5% (3/40), while the oneyear all-cause mortality rate was 2.5% (1/40). While one patient died owing to severe pancreatitis, no serious adverse events related to tigecycline therapy were reported. However, multiple indices of liver function and pancreatitis precursors increased after treatment with tigecycline compared to before treatment. Conclusion: Tigecycline therapy appears to be well tolerated in renal transplant recipients with multidrug-resistant bacterial infections. Nevertheless, attention should be paid to adverse reactions related to tigecycline therapy, especially gastrointestinal reactions, and the related laboratory tests should be closely monitored. [ABSTRACT FROM AUTHOR]

Background: The appropriate administration regimen of polymyxin B is yet controversial. The present study aimed to explore the optimal dose of polymyxin B under therapeutic drug monitoring (TDM) guidance. Methods: In China's Henan province, 26 hospitals participated in a randomized controlled trial. We included patients with sepsis caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) susceptible to polymyxin B. The patients were randomly divided into a high-dose (HD) group or a low-dose (LD) group and received 150 mg loading dose, 75 mg every 12 h and 100 mg loading dose, 50 mg every 12 h, respectively. TDM was employed to determine if the dose of polymyxin B needs adjustment based on the area under the concentration–time curve across 24 h at a steady state (ssAUC0–24) of 50–100 mg h/L. The primary outcome was the 14-day clinical response, and the secondary outcomes included 28- and 14-day mortality. Results: This trial included 311 patients, with 152 assigned to the HD group and 159 assigned to the LD group. Intention-to-treat analysis showed that the 14-day clinical response was non-significant (p = 0.527): 95/152 (62.5%) in the HD group and 95/159 (59.7%) in the LD group. Kaplan–Meier's 180-day survival curve showed survival advantage in the HD group than in the LD group (p = 0.037). More patients achieved the target ssAUC0–24 in the HD than in the LD group (63.8% vs. 38.9%; p = 0.005) and in the septic shock subgroup compared to all subjects (HD group: 71.4% vs. 63.8%, p = 0.037; LD group: 58.3% vs. 38.9%, p = 0.0005). Also, the target AUC compliance was not correlated with clinical outcomes but with acute kidney injury (AKI) (p = 0.019). Adverse events did not differ between the HD and LD groups. Conclusion: A fixed polymyxin B loading dose of 150 mg and a maintenance dose of 75 mg every 12 h was safe for patients with sepsis caused by CR-GNB and improves long-term survival. The increased AUC was associated with increased incidence of AKI, and TDM results were valued to prevent AKI. Trial registration Trial registration ClinicalTrials.gov: ChiCTR2100043208, Registration date: January 26, 2021. [ABSTRACT FROM AUTHOR]

Limited data on clinical and microbiological efficacy, patient mortality, and other associated factors are available for ceftazidime/avibactam (CAZ/AVI)-based regimens for carbapenem-resistant Gram-negative bacteria (CR-GNB). This study aimed to assess these issues retrospectively using multicenter data. This multicenter study included CR-GNB infected patients treated with CAZ/AVI-based regimens for more than three days. Patient characteristics, bacterial culture reports, drug-sensitivity test results, and antibiotic use, including CAZ/AVI use, were extracted from the patient's clinical records. The clinical and microbiological efficacy of the combined drug regimen and patient mortality were evaluated according to corresponding definitions. Univariate and multivariate logistic regressions were performed to explore the efficacy and mortality-related factors. A total of 183 patients with CR-GNB infection were considered for the analysis according to the inclusion and exclusion criteria. After the treatment of CAZ/AVI-based regimens, the clinical efficacy was 75.4 %. The 7-day microbial efficacy and clearance rate after treatment were 43.7 % and 66.0 %, respectively. Moreover, 30-day all-cause and in-hospital mortality were 11.5 % and 14.2 %, respectively. Harboring renal dysfunction (creatinine clearance rate (CCR) of<20 mL/min), cardiovascular diseases, and digestive system diseases were independent risk factors for poor clinical efficacy of CAZ/AVI-based regimens. Bloodstream infection (BSI), patients with the adjusted doses of CAZ/AVI, and CAZ/AVI co-administration with carbapenem were independently associated factors of bacterial clearance by CAZ/AVI-based regimens. Age, total hospital stays, use of mechanical ventilation, and cumulative CAZ/AVI dose were independent factors associated with all-cause mortality. CAZ/AVI was an effective drug in treating CR-GNB infection. CAZ/AVI that is mostly excreted by the kidney and is accumulated in renal impairment should be renally adjusted. Renal dysfunction and the adjusted dose of CAZ/AVI were associated with efficacy. Clinicians should individualize CAZ/AVI regimen and dose by the level of renal function to achieve optimal efficacy and survival. The efficacy of CAZ/AVI in the treatment of CR-GNB infection, as well as the implementation of individualized precision drug administration of CAZ/AVI according to patients' different infection sites, renal function, bacterial types, bacterial resistance mechanisms, blood concentration monitoring and other conditions need to be further studied in multicenter. [ABSTRACT FROM AUTHOR]

Abstract Background Patients with cancer are at risk of multidrug-resistant bacteria colonization, but association of colonization with in-hospital mortality and one-year survival has not been established in critically ill patients with cancer. Methods Using logistic and Cox-regression analyses adjusted for confounders, in adult patients admitted at intensive care unit (ICU) with active cancer, we evaluate the association of colonization by carbapenem-resistant Gram-negative bacteria or vancomycin-resistant enterococci with in-hospital mortality and one-year survival. Results We included 714 patients and among them 140 were colonized (19.6%). Colonized patients more frequently came from ward, had longer hospital length of stay before ICU admission, had unplanned ICU admission, had worse performance status, higher predicted mortality upon ICU admission, and more hematological malignancies than patients without colonization. None of the patients presented conversion of colonization to infection by the same bacteria during hospital stay, but 20.7% presented conversion to infection after hospital discharge. Colonized patients had a higher in-hospital mortality compared to patients without colonization (44.3 vs. 33.4%; p

Abstract Background Tigecycline has in vitro bacteriostatic activity against a broad spectrum of bacteria, including carbapenem-resistant Gram-negative bacteria (CR-GNB). However, the role of tigecycline in treatment of nosocomial pneumonia caused by CR-GNB remains controversial and clinical evidences are limited. We aimed to investigate the clinical benefits of tigecycline as part of the combination treatment of nosocomial CR-GNB pneumonia in intensive care unit (ICU). Methods This multi-centre cohort study retrospectively enrolled ICU-admitted patients with nosocomial pneumonia caused by CR-GNB. Patients were categorized based on whether add-on tigecycline was used in combination with at least one anti-CR-GNB antibiotic. Clinical outcomes and all-cause mortality between patients with and without tigecycline were compared in the original and propensity score (PS)-matched cohorts. A subgroup analysis was also performed to explore the differences of clinical efficacies of add-on tigecycline treatment when combined with various anti-CR-GNB agents. Results We analysed 395 patients with CR-GNB nosocomial pneumonia, of whom 148 received tigecycline and 247 did not. More than 80% of the enrolled patients were infected by CR-Acinetobacter baumannii (CRAB). A trend of lower all-cause mortality on day 28 was noted in tigecycline group in the original cohort (27.7% vs. 36.0%, p = 0.088). In PS-matched cohort (102 patient pairs), patients with tigecycline had significantly lower clinical failure (46.1% vs. 62.7%, p = 0.017) and mortality rates (28.4% vs. 52.9%, p

Abstract Background Carbapenem-resistant gram-negative bacteria (CRGNB) have become a public health concern worldwide. The risk factors associated with CRGNB infection after colonization are unknown, nor is the optimal timing of antibiotic treatment, warranting further investigation. Methods A 4-year single-center prospective observational study was conducted. CRGNB-colonized patients were incorporated on admission into our observation cohort for an active surveillance culture program, and analysis of risk factors associated with infections after CRGNB colonization was performed. We divided patients into empirical antibiotic therapy groups and standard antibiotic therapy groups according to whether antibiotics were used before or after cultures yielded a result to explore the relationship between the timing of antibiotics and clinical efficacy. Results 152 out of 451 CRGNB-colonized patients in the prospective observational cohort developed CRGNB infection. The risk factors associated with CRGNB infection after colonization included CRKP (P

ABSTRACT: Objectives: This study constructed a carbapenem-resistant Gram-negative bacteria (CR-GNB) carriage prediction model to predict the CR-GNB incidence in a week. Methods: We used our database to select patients with complete CR-GNB screening records between the years 2015 and 2019 and constructed the model using multivariable logistic regression and three machine learning algorithms. Then we chose the optimal model and verified the accuracy by daily prediction and recorded the occurrence of CR-GNB in all intensive care unit patients admitted for 4 months. Results: There were 1385 patients with positive CR-GNB cultures and 1535 negative patients in this study. Forty-five variables had statistically significant differences. We included 16 variables in the multivariable logistic regression model and built three machine learning models for all variables. In terms of accuracy and the area under the receiver operating characteristic (AUROC) curve, random forest was better than XGBoost and decision tree and better than a multivariable logistic regression model (accuracy: 84%>82%>81%>72%, AUROC: 0.91>0.89=0.89>0.78). In a 4-month prospective study, 74 cases were predicted to have positive CR-GNB culture within 7 days, 132 cases were predicted to be negative, 86 cases were positive, and 120 cases were negative, with an overall accuracy of 85.92% and AUROC of 92.02%. Conclusion: Machine learning prediction models can predict the occurrence of CR-GNB colonisation or infection within a one-week period and can guide medical staff in real time to identify high-risk groups more accurately.

Background: Patients with cancer are at risk of multidrug-resistant bacteria colonization, but association of colonization with in-hospital mortality and one-year survival has not been established in critically ill patients with cancer. Methods: Using logistic and Cox-regression analyses adjusted for confounders, in adult patients admitted at intensive care unit (ICU) with active cancer, we evaluate the association of colonization by carbapenem-resistant Gram-negative bacteria or vancomycin-resistant enterococci with in-hospital mortality and one-year survival. Results: We included 714 patients and among them 140 were colonized (19.6%). Colonized patients more frequently came from ward, had longer hospital length of stay before ICU admission, had unplanned ICU admission, had worse performance status, higher predicted mortality upon ICU admission, and more hematological malignancies than patients without colonization. None of the patients presented conversion of colonization to infection by the same bacteria during hospital stay, but 20.7% presented conversion to infection after hospital discharge. Colonized patients had a higher in-hospital mortality compared to patients without colonization (44.3 vs. 33.4%; p < 0.01), but adjusting for confounders, colonization was not associated with in-hospital mortality [Odds ratio = 1.03 (0.77–1.99)]. Additionally, adjusting for confounders, colonization was not associated with one-year survival [Hazard ratio = 1.10 (0.87–1.40)]. Conclusions: Adult critically ill patients with active cancer and colonized by carbapenem-resistant Gram-negative bacteria or vancomycin-resistant enterococci active cancer have a worse health status compared to patients without colonization. However, adjusting for confounders, colonization by carbapenem-resistant Gram-negative bacteria or vancomycin-resistant enterococci are not associated with in-hospital mortality and one-year survival. [ABSTRACT FROM AUTHOR]

Background: With the number of critically ill patients increasing in gastroenterology departments (GEDs), infections associated with Carbapenem-resistant Gram-negative bacteria (CR-GNB) are of great concern in GED. However, no CR-GNB bloodstream infection (BSI) risk prediction model has been established for GED patients. Almost universally, CR-GNB colonization precedes or occurs concurrently with CR-GNB BSI. The objective of this study was to develop a nomogram that could predict the risk of acquiring secondary CR-GNB BSI in GED patients who are carriers of CR-GNB. Methods: We conducted a single-center retrospective case–control study from January 2020 to March 2022. Univariate and multivariable logistic regression analysis was used to identify independent risk factors of secondary CR-GNB bloodstream infections among CR-GNB carriers in the gastroenterology department. A nomogram was constructed according to a multivariable regression model. Various aspects of the established predicting nomogram were evaluated, including discrimination, calibration, and clinical utility. We assessed internal validation using bootstrapping. Results: The prediction nomogram includes the following predictors: high ECOG PS, severe acute pancreatitis, diabetes mellitus, neutropenia, a long stay in hospital, and parenteral nutrition. The model demonstrated good discrimination and good calibration. Conclusions: With an estimate of individual risk using the nomogram developed in this study, clinicians and nurses can identify patients with a high risk of secondary CR-GNB BSI early. [ABSTRACT FROM AUTHOR]

In this study, we analyzed the antibiotic resistance of carbapenem-resistant gramnegative bacteria (CR-GNB) in intensive care unit (ICU) patients and developed a predictive model. We retrospectively collected the data of patients with GNB infection admitted to the ICU of the First Affiliated Hospital of Fujian Medical University, who were then divided into a CR and a carbapenem-susceptible (CS) group for CR-GNB infection analysis. Patients admitted between December 1, 2017, and July 31, 2019, were assigned to the experimental cohort (n = 205), and their data were subjected to multivariate logistic regression analysis to identify independent risk factors for constructing the nomogram-based predictive model. Patients admitted between August 1, 2019, and September 1, 2020, were assigned to the validation cohort for validating the predictive model (n = 104). The Hosmer −Lemeshow test and receiver operating characteristic (ROC) curve analysis were used to validate the model’s performance. Overall, 309 patients with GNB infection were recruited. Of them, 97 and 212 were infected with CS-GNB and CR-GNB, respectively. Carbapenem-resistant Klebsiella pneumoniae (CRKP), carbapenemresistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) were the most prevalent CR-GNB. The multivariate logistic regression analysis results of the experimental cohort revealed that a history of combination antibiotic treatments (OR: 3.197, 95% CI: 1.561–6.549), hospital-acquired infection (OR: 3.563, 95% CI: 1.062–11.959) and mechanical ventilation ≥ 7 days (OR: 5.096, 95% CI: 1.865–13.923) were independent risk factors for CR-GNB infection, which were then used for nomogram construction. The model demonstrated a good fit of observed data (p = 0.999), with an area under the ROC curve (AUC) of 0.753 (95% CI: 0.685– 0.820) and 0.718 (95% CI: 0.619–0.816) for the experimental and validation cohort, respectively. The decision curve analysis results suggested that the model has a high practical value for clinical practice. The Hosmer−Lemeshow test indicated a good fit of the model in the validation cohort (p-value, 0.278). Overall, our proposed predictive model exhibited a good predictive value in identifying patients at high risk of developing CR-GNB infection in the ICU and could be used to guide preventive and treatment measures. [ABSTRACT FROM AUTHOR]

Background: Tigecycline has in vitro bacteriostatic activity against a broad spectrum of bacteria, including carbapenem-resistant Gram-negative bacteria (CR-GNB). However, the role of tigecycline in treatment of nosocomial pneumonia caused by CR-GNB remains controversial and clinical evidences are limited. We aimed to investigate the clinical benefits of tigecycline as part of the combination treatment of nosocomial CR-GNB pneumonia in intensive care unit (ICU). Methods: This multi-centre cohort study retrospectively enrolled ICU-admitted patients with nosocomial pneumonia caused by CR-GNB. Patients were categorized based on whether add-on tigecycline was used in combination with at least one anti-CR-GNB antibiotic. Clinical outcomes and all-cause mortality between patients with and without tigecycline were compared in the original and propensity score (PS)-matched cohorts. A subgroup analysis was also performed to explore the differences of clinical efficacies of add-on tigecycline treatment when combined with various anti-CR-GNB agents. Results: We analysed 395 patients with CR-GNB nosocomial pneumonia, of whom 148 received tigecycline and 247 did not. More than 80% of the enrolled patients were infected by CR-Acinetobacter baumannii (CRAB). A trend of lower all-cause mortality on day 28 was noted in tigecycline group in the original cohort (27.7% vs. 36.0%, p = 0.088). In PS-matched cohort (102 patient pairs), patients with tigecycline had significantly lower clinical failure (46.1% vs. 62.7%, p = 0.017) and mortality rates (28.4% vs. 52.9%, p < 0.001) on day 28. In multivariate analysis, tigecycline treatment was a protective factor against clinical failure (PS-matched cohort: aOR 0.52, 95% CI 0.28–0.95) and all-cause mortality (original cohort: aHR 0.69, 95% CI 0.47–0.99; PS-matched cohort: aHR 0.47, 95% CI 0.30–0.74) at 28 days. Kaplan–Meier survival analysis in subgroups of patients suggested significant clinical benefits of tigecycline when added to a colistin-included (log rank p value 0.005) and carbapenem-included (log rank p value 0.007) combination regimen. Conclusions: In this retrospective observational study that included ICU-admitted patients with nosocomial pneumonia caused by tigecycline-susceptible CR-GNB, mostly CRAB, tigecycline as part of a combination treatment regimen was associated with lower clinical failure and all-cause mortality rates. [ABSTRACT FROM AUTHOR]

Purpose: Infections with carbapenem-resistant gram-negative bacteria (in Germany classified as 4MRGN) are a growing threat in clinical care. This study was undertaken to understand the overall burden of 4MRGN infections in Germany in the context of a Health Technology Appraisal (HTA) for Ceftazidime/Avibactam (CAZ/AVI). Besides, the incidences mortality was an endpoint of interest. Methods: To assess infections with carbapenem-resistant gram-negative bacteria and related mortality, three different data sources have been used. From the German statistics office (DESTATIS) data have been retrieved to obtain the overall frequency these pathogens. Via two other databases, the German analysis database (DADB) and a Benchmarking of > 200 hospitals in a representative sample (BM-DB), the distribution of the infections and the mortality have been analyzed. Results: DESTATIS data showed a total of 11,863 carbapenem-resistant gram-negative bacteria codings, of which 10,348 represent infections and 1515 carriers. The most frequent infections were complicated urinary tract infections (cUTI) (n = 2,337), followed by pneumonia (n = 1006) and intra-abdominal infections (n = 730). A considerable amount of patients had multiple infections in one hospital episode (n = 1258). In-hospital mortality was 18.6% in DADB and 14.3% in the BM-DB population, respectively. In cases with additional bloodstream infections, DADB mortality was correspondingly higher at 33.0%. DADB data showed an incremental mortality increase of 5.7% after 30 days and 10.0% after 90 days resulting in a cumulative 90 day mortality of 34.3%. Conclusions: Infections with carbapenem-resistant gram-negative bacteria are still rare (6.8–12.4 per 100,000) but show a significant increase in mortality compared to infections with more sensitive pathogens. Using different data sources allowed obtaining a realistic picture. [ABSTRACT FROM AUTHOR]

Jian Qu,1,2 Ting-Ting Qi,1,2 Qiang Qu,3,4 Wen-Ming Long,5 Ying Chen,6 Yue Luo,7 Ying Wang1,2 1Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, 410011, People’s Republic of China; 2Institute of Clinical Pharmacy, Central South University, Changsha, 410011, People’s Republic of China; 3Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410078, People’s Republic of China; 4National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410078, People’s Republic of China; 5Department of Pharmacy, Jingzhou District, Second People’s Hospital of Huaihua City, Huaihua, 418400, People’s Republic of China; 6Department of Pharmacy, Wuhan University, Renmin Hospital, Wuhan, 430060, People’s Republic of China; 7Department of Pharmacy, The People’s Hospital of Liuyang, Liuyang, 410300, People’s Republic of ChinaCorrespondence: Ying Wang, Department of Pharmacy, The Second Xiangya Hospital, Central South University, Institute of Clinical Pharmacy, Central South University, No. 139 Middle Renmin Road, Changsha, 410011, People’s Republic of China, Tel +86-15173198700, Fax +86-731-85292072, Email wangying5211@csu.edu.cnBackground: The increasing prevalence of carbapenem-resistant Gram-negative bacteria (CR-GNB) represents a global healthcare crisis. This study explored the efficacy and safety of Polymyxin B (PMB)-based regimens and factors influencing their effectiveness.Methods: Patients with CR-GNB infections treated with PMB for more than three days were enrolled in this retrospective study from 1st June 2018 to 30th April 2020. Data were collected on patient characteristics, bacterial culture, and drug-sensitivity test results; anti-infection treatment regimens, particularly details of PMB use; and adverse drug reactions. Clinical and microbiological efficacy, mortality, and safety of PMB-based regimens in CR-GNB infected patients were evaluated. Univariate analysis and multivariate logistic regression analyses were used to assess factors influencing efficacy and mortality.Results: A total of 373 CR-GNB strains were cultured from 268 patients. About 41.04% of patients used PMB loading dose of 1.01 (0.84– 1.69) mg/kg. Maintenance dose was 0.85 (0.82– 1.00) mg/kg q12h. The clinical efficacy rate was 36.57% (98/268), the total bacterial clearance rate of PMB was 39.42%, and the all-cause mortality rate was 33.96%. The adverse drug reaction rate was 19.58%, among which the incidence of renal toxicity was highest (8.21%). Multivariate logistic regression analysis showed that clinical efficacy, bacterial clearance rate, and all-cause mortality were associated with patient-related facts, including mechanical ventilation use, underlying diseases (such as respiratory disease), the type and site of CR-GNB infection, and PMB administration timing and loading dose.Conclusion: PMB is a relatively safe and effective antibiotic drug for treatment of critically ill patients with CR-GNB infection; however, PMB use should be subject to guidelines recommendations for early administration, loading administration, and adequate administration, which could help to improve the clinical efficacy, microbiological efficacy, and mortality.Keywords: polymyxin B, carbapenem-resistant Gram-negative bacteria, clinical efficacy, bacterial elimination, mortality, adverse effect

Multidrug-resistant (MDR) Gram-negative bacteria (GNB) have raised concerns as common, frequent etiologic agents of nosocomial infections, and patients admitted to intensive care units (ICUs) present the highest risk for colonization and infection. The incidence of colonization and infection in trauma patients remains poorly investigated. The aim of this study was to assess the risk factors for Carbapenem-resistant (CR)-GNB colonization and the clinical impact of colonization acquisition in patients with severe trauma admitted to the ICU in a CR-GNB hyperendemic country. This is a retrospective observational study; clinical and laboratory data were extracted from the nosocomial infection surveillance system database. Among 54 severe trauma patients enrolled in the study, 28 patients were colonized by CR-GNB; 7 (12.96%) patients were already colonized at ICU admission; and 21 (38.89%) patients developed a new colonization during their ICU stay. Risk factors for colonization were the length of stay in the ICU (not colonized, 14.81 days ± 9.1 vs. colonized, 38.19 days ± 27.9; p-value = 0.001) and days of mechanical ventilation (not colonized, 8.46 days ± 7.67 vs. colonized, 22.19 days ± 15.09; p-value < 0.001). There was a strong statistical association between previous colonization and subsequent development of infection (OR = 80.6, 95% CI 4.5–1458.6, p-value < 0.001). Factors associated with the risk of infection in colonized patients also included a higher Charlson comorbidity index, a longer length of stay in the ICU, a longer duration of mechanical ventilation, and a longer duration of treatment with carbapenem and vasopressors (not infected vs. infected: 0(0–4) vs. 1(0–3), p = 0.012; 24.82 ± 16.77 vs. 47 ± 28.51, p = 0.016; 13.54 ± 15.84 vs. 31.7 ± 16.22, p = 0.008; 1.09 ± 1.14 vs. 7.82 ± 9.15, p = 0.008). The adoption of MDR-GNB colonization prevention strategies in critically ill patients with severe trauma is required to improve the quality of care and reduce nosocomial infections, length of hospital stay and mortality. [ABSTRACT FROM AUTHOR]

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Polymyxins was applied to treat ventilator associated pneumonia (VAP) caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) via different administration routes. The potential benefits of aerosolised polymyxins as adjunctive treatment for patients still were contradictory. This review assessed the safety and efficacy of intravenous combined with aerosolised polymyxins versus intravenous polymyxins monotherapy in patients with VAP caused by CR-GNB. Two reviewers independently evaluated and extracted date from Pubmed, Embase, Cochrane library and Web of science. The primary outcome was all-cause mortality and secondary outcomes included clinical cure rate, clinical improvement rate, microbiological eradication and nephrotoxicity. Differences for dichotomous outcomes were expressed as odds ratios (OR) with 95% confidence intervals (CI). Eleven eligible studies were included. The results showed that compared with intravenous polymyxins monotherapy, intravenous plus aerosolised polymyxins therapy significantly reduced all-cause mortality rate (OR = 0.75, 95% CI 0.57 - 0.99, P = 0.045) and improved clinical improvement rate (OR = 1.62, 95% CI 1.02 - 2.60, P = 0.043) and microbial eradication rate (OR = 2.07, 95% CI 1.40 - 3.05, P = 0.000). However, there were no significant difference in terms of clinical cure rate (OR = 1.59, 95% CI 0.96 - 2.63, P = 0.072) and nephrotoxicity (OR = 1.14, 95% CI 0.80 - 1.63, P = 0.467) for intravenous plus aerosolised polymyxins therapy. Subgroup analysis revealed that the clinical improvement rate was improved significantly in case-control studies. Aerosolised polymyxins maybe a useful adjunct to intravenous polymyxins for CR-GNB VAP patients., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Ltd.)

The wide spread of carbapenemases among gram-negative bacteria of the Enterobacterales order in hospitals around the world, including Russia, creates great difficulties in the effective use of antibiotics for these infections in the ICU. Ceftazidime-avibactam is the first antibiotic developed and studied for the treatment of infections caused by carbapenem-resistant enterobacteria. Ceftazidime-avibactam shows high activity against producers of class A and D serine carbapenemases (KPC and OXA-48). In combination with aztreonam it is effective in infections caused by producers of class B metallo-beta-lactamases (NDM and VIM). The review analyzes the results of 19 non-comparative and 10 comparative studies of ceftazidime-avibactam in infections caused by carbapenem-resistant Enterobacterales, as well as case reports. According to the data of non- comparative studies, the clinical efficacy of ceftazidime-avibactam ranged from 45.0 to 87.2%, on average 71.7±11.3%, and the eradication rate of KPC or OXA-48 carbapenemase producers ranged from 40.0 to 100%, on average 65.5±18.6%. The effectiveness of ceftazidime-avibactam in comparative studies was 67.9±17.3%, which was significantly higher compared to other antibiotics (44.3±14.4%, P=0.012). Treatment with ceftazidime-avibactam was accompanied by a significantly lower 30-day mortality in contrast to other antibiotics – 23.8±13.5% and 41.0±13.6%, respectively, P=0.001. The development of resistance in Enterobacterales species to ceftazidime-avibactam during therapy is rarely observed, on average 5.4±4.4%, which characterizes a rather low potential of the antibiotic in resistance selection. Early administration of ceftazidime-avibactam is accompanied by better treatment results as opposed to delayed therapy. Treatment of infections caused by carbapenem-resistant enterobacteria with ceftazidime-avibactam is associated with a significantly higher recovery rate and a lower mortality compared to other regimens of antibacterial therapy.

Background: Carbapenem-resistant gram-negative bacteria (CRGNB) have become a public health concern worldwide. The risk factors associated with CRGNB infection after colonization are unknown, nor is the optimal timing of antibiotic treatment, warranting further investigation. Methods: A 4-year single-center prospective observational study was conducted. CRGNB-colonized patients were incorporated on admission into our observation cohort for an active surveillance culture program, and analysis of risk factors associated with infections after CRGNB colonization was performed. We divided patients into empirical antibiotic therapy groups and standard antibiotic therapy groups according to whether antibiotics were used before or after cultures yielded a result to explore the relationship between the timing of antibiotics and clinical efficacy. Results: 152 out of 451 CRGNB-colonized patients in the prospective observational cohort developed CRGNB infection. The risk factors associated with CRGNB infection after colonization included CRKP (P < 0.001, OR = 3.27) and CRPA (P < 0.001, OR = 2.97) colonization, history of carbapenems use (P < 0.001, OR = 5.48), and immunocompromise (P < 0.001, OR = 7.07). There were 88 infected patients in the empirical antibiotic therapy groups and 64 in standard antibiotic therapy groups. The mortality was lower in empirical therapy groups than standard therapy groups (17.0% vs. 37.5%, P = 0.004, OR = 0.32). Conclusions: CRGNB colonized patients who are prone to infection have some high-risk factors included CRKP and CRPA colonization, immunocompromise, and prior carbapenems use. Once infection occurs in CRGNB-colonized patients, early use of effective antibiotics may be associated with reduced mortality, but more studies are needed. [ABSTRACT FROM AUTHOR]

ABSTRACT Carbapenem-resistant Gram-negative bacteria (CRGNB)-related health care-associated ventriculitis and meningitis (HCAVM) is dangerous. We aimed to report the antimicrobial resistance of the pathogens, treatment, and outcome. All cases with CRGNB-related HCAVM in2012–2020 were recruited. Antimicrobial agents were classified as active, untested, or inactive using antimicrobial susceptibility tests. The treatment stage was classified as empirical or targeted according to the report of pathogens. The treatment effect was classified as ineffective or effective according to HCAVM-related parameters. Overall, 92 cases were recruited. For most antimicrobial agents, the resistance rate was higher than 70.0%. The polymyxin resistance rate was the lowest at 11.6%. The chloramphenicol, trimethoprim-sulfamethoxazole, amikacin, levofloxacin, and tetracycline resistance rates were relatively low, ranging from 21.1% to 64.1%. The meropenem resistance rate was 81.9%. There was no significant trend for any antimicrobial agent tested. Meropenem was the most common antimicrobial agent used in empirical treatment; trimethoprim-sulfamethoxazole and polymyxin were the most used active antimicrobial agents, and meropenem/sulbactam and polymyxin were the most used untested antimicrobial agents in targeted treatment. In total, 42 (45.7%) cases received ineffective treatments. The ineffective treatment rate of cases that received active antimicrobial agents was lower than that of cases that received untested antimicrobial agents and cases that received inactive antimicrobial agents (29.3% [12/41] versus 46.2% [18/39] versus 100.0% [12/12], P < 0.001). Antimicrobial resistance was prevalent but without increasing trends. Active antimicrobial agents are necessary. Additionally, untested antimicrobial agents, including meropenem/sulbactam and polymyxin, might be optional. Inactive antimicrobial agents must be replaced. IMPORTANCE Carbapenem-resistant Gram-negative bacteria-related health care-associated ventriculitis and meningitis is a clinical threat because of the poor outcome and challenges in treatment. We reached several conclusions: (i) the antimicrobial resistance of pathogens is severe, and some antimicrobial agents represented by polymyxin are optional according to the antimicrobial susceptibility tests; (ii) in the background that the portion of carbapenems resistance in Gram-negative bacteria is increasing, there is no increasing trend for the antimicrobial resistance of carbapenem-resistant Gram-negative bacteria in the 9-year study; (iii) meropenem is the main antimicrobial agent in treatment, and trimethoprim-sulfamethoxazole, tigecycline, polymyxin, and meropenem/sulbactam are commonly used in the targeted treatment; (iv) the treatment effect was poor and affected by the treatment: timely active antimicrobial agents should be given. And untested antimicrobial agents represented by polymyxin and meropenem/sulbactam might be optional. Inactive antimicrobial agents must be replaced.

Background: This study investigated the high-risk factors associated with the increased vulnerability for subsequent clinical CR-GNB infection in carbapenem-resistant Gram-negative bacteria (CR-GNB)-colonized hematological malignancy (HM) patients and built a statistical model to predict subsequent infection. Method: All adult HM patients with positive rectoanal swabs culture for CR-GNB between January 2018 and June 2020 were prospectively followed to assess for any subsequent CR-GNB infections and to investigate the risk factors and clinical features of subsequent infection. Results: A total of 392 HM patients were enrolled. Of them, 46.7% developed a subsequent clinical CR-GNB infection, with 42 (10.7%) cases of confirmed infection and 141 (36%) cases of clinically diagnosed infection. Klebsiella pneumoniae was the dominant species. The overall mortality rate of patients colonized and infected with CR-GNB was 8.6% and 43.7%. A multivariate analysis showed that remission induction chemotherapy and the duration of agranulocytosis, mucositis, and hypoalbuminemia were significant predictors of subsequent infection after CR-GNB colonization. According to our novel risk-predictive scoring model, the high-risk group were >3 times more likely to develop a subsequent infection in comparison with the low-risk group. Conclusion: Our risk-predictive scoring model can early and accurately predict a subsequent CR-GNB infection in HM patients with CR-GNB colonization. The early administration of CR-GNB-targeted empirical therapy in the high-risk group is strongly recommended to decrease their mortality. [ABSTRACT FROM AUTHOR]

Polymyxin B (PMB), a kind of polymyxin, was widely used in carbapenem-resistant Gram-negative bacterial (CR-GNB) infections. However, adverse reactions such as nephrotoxicity and neurotoxicity limit its use in clinical practice. The aim of this study was to explore PMB associated with nephrotoxicity and its predictors. Patients who received PMB intravenous drip for more than 72 h were eligible for the study. Characteristics of patients, concomitant nephrotoxic agents, underlying disease, and antimicrobial susceptibility were submitted for descriptive analysis. Univariate analysis and binary logistic regression were used to assess the factors leading to acute kidney injury (AKI). AKI was assessed with serum creatinine variations according to the classification of risk (stage R), injury (stage I), failure (stage F), loss, and end-stage of kidney disease. Among 234 patients with CR-GNB infections who used PMB in our study, 67 (28.63%) patients developed AKI, including 31 (14.25%) patients in stage R, 15 (6.41%) patients in stage I, and 21 (8.97%) patients in stage F. The incident rate of PMB-related nephrotoxicity in patients with normal renal function was 32.82% (43/131). The higher risk factors of AKI include males [odds ratio (OR) = 3.237; 95% confidence interval (95%CI) = 1.426–7.350], digestive system diseases [OR = 2.481 (1.127–5.463)], using furosemide (>20 mg/day) [OR = 2.473 (1.102–5.551)], and baseline serum creatinine [OR = 0.994 (0.990–0.999)]. Nonparametric tests of K-independent samples showed that baseline serum creatinine and the PMB maintenance dose were associated with the severity of nephrotoxicity (both p < 0.05). Male, digestive system diseases, using furosemide (>20 mg/day), and high baseline serum creatinine were the independent risk factors of PMB-associated AKI development. The maintenance dose of PMB may be related to the severity of AKI. These risk factors should be taken into consideration when initiating PMB-based therapy. The serum creatinine value should be closely monitored when using PMB. [ABSTRACT FROM AUTHOR]

BackgroundThis study investigated the high-risk factors associated with the increased vulnerability for subsequent clinical CR-GNB infection in carbapenem-resistant Gram-negative bacteria (CR-GNB)-colonized hematological malignancy (HM) patients and built a statistical model to predict subsequent infection.MethodAll adult HM patients with positive rectoanal swabs culture for CR-GNB between January 2018 and June 2020 were prospectively followed to assess for any subsequent CR-GNB infections and to investigate the risk factors and clinical features of subsequent infection.ResultsA total of 392 HM patients were enrolled. Of them, 46.7% developed a subsequent clinical CR-GNB infection, with 42 (10.7%) cases of confirmed infection and 141 (36%) cases of clinically diagnosed infection. Klebsiella pneumoniae was the dominant species. The overall mortality rate of patients colonized and infected with CR-GNB was 8.6% and 43.7%. A multivariate analysis showed that remission induction chemotherapy and the duration of agranulocytosis, mucositis, and hypoalbuminemia were significant predictors of subsequent infection after CR-GNB colonization. According to our novel risk-predictive scoring model, the high-risk group were >3 times more likely to develop a subsequent infection in comparison with the low-risk group.ConclusionOur risk-predictive scoring model can early and accurately predict a subsequent CR-GNB infection in HM patients with CR-GNB colonization. The early administration of CR-GNB-targeted empirical therapy in the high-risk group is strongly recommended to decrease their mortality.

Polymyxin B (PMB), a kind of polymyxin, was widely used in carbapenem-resistant Gram-negative bacterial (CR-GNB) infections. However, adverse reactions such as nephrotoxicity and neurotoxicity limit its use in clinical practice. The aim of this study was to explore PMB associated with nephrotoxicity and its predictors. Patients who received PMB intravenous drip for more than 72 h were eligible for the study. Characteristics of patients, concomitant nephrotoxic agents, underlying disease, and antimicrobial susceptibility were submitted for descriptive analysis. Univariate analysis and binary logistic regression were used to assess the factors leading to acute kidney injury (AKI). AKI was assessed with serum creatinine variations according to the classification of risk (stage R), injury (stage I), failure (stage F), loss, and end-stage of kidney disease. Among 234 patients with CR-GNB infections who used PMB in our study, 67 (28.63%) patients developed AKI, including 31 (14.25%) patients in stage R, 15 (6.41%) patients in stage I, and 21 (8.97%) patients in stage F. The incident rate of PMB-related nephrotoxicity in patients with normal renal function was 32.82% (43/131). The higher risk factors of AKI include males [odds ratio (OR) = 3.237; 95% confidence interval (95%CI) = 1.426–7.350], digestive system diseases [OR = 2.481 (1.127–5.463)], using furosemide (>20 mg/day) [OR = 2.473 (1.102–5.551)], and baseline serum creatinine [OR = 0.994 (0.990–0.999)]. Nonparametric tests of K-independent samples showed that baseline serum creatinine and the PMB maintenance dose were associated with the severity of nephrotoxicity (both p < 0.05). Male, digestive system diseases, using furosemide (>20 mg/day), and high baseline serum creatinine were the independent risk factors of PMB-associated AKI development. The maintenance dose of PMB may be related to the severity of AKI. These risk factors should be taken into consideration when initiating PMB-based therapy. The serum creatinine value should be closely monitored when using PMB.

Objective To investigate the clinical efficacy of polymyxin B based combination therapy on patients with carbapenem-resistant gram-negative bacterial (CR-GNB) sepsis. Methods Clinical data of 48 patients with sepsis who used polymyxin B as the basis for combination therapy of CR-GNB infection were retrospectively analyzed. (1) According to the time from specimen collecting for inspection to the start of the use of polymyxin B, patients were divided into the early group (≤7 days, n=30) and the delayed group (＞7 days, n=18). (2) According to the duration of polymyxin B therapy, patients were divided into the ≤ 7 days group (n=16) and the ＞7 days group (n=32). (3) According to the different combination of polymyxin B-based therapy, patients were divided into the tegacyclin group (n=23), the carbapenem group (n=9) and the other drug groups (piperacillin tazobactam, cefoperazone sulbactam, ciprofloxacin and etimicin, n=16). The total bacterial clearance rate, effective rate and 28-d mortality were compared between groups. Results (1) The total bacterial clearance rate (76.7% vs. 44.4%, χ2=5.107, P＜0.05) and the efficacy rate (73.3% vs. 44.4%, χ2=4.006, P＜0.05) after therapy were higher in the early group than those in the delayed group. There was no significant difference in the 28-day mortality between the two groups (30.0% vs. 38.9%, χ2=0.400, P＞0.05). The total bacterial clearance rate (78.1% vs. 37.5%, χ2= 7.696, P＜0.01), efficacy rate (75.0% vs. 37.5%, χ2= 6.400, P＜0.05) and 28-day mortality (21.9% vs. 56.3%, χ2=5.672, P＜ 0.05) were significantly improved in the therapy duration ＞7-day group compared with the therapy duration ≤ 7-day group. (3) In the combination therapy of polymyxin B, total bacterial clearance rate (69.6% vs. 66.7% vs. 56.3%, χ2=0.823), efficacy rate (69.6% vs. 55.6% vs. 56.3%, χ2=1.051) and 28-day mortality (26.1% vs. 33.3% vs. 43.8%, χ2=1.390) showed no significant difference between the tegacyclin group, the carbapenem group and the other drug groups (all P＞0.05). Conclusion Polymyxin B should be used in combination with other anti-infective drugs in the early stage and sufficient course of therapy for patients with CR-GNB infected sepsis. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to forecast the monthly incidence rates of infections [infections/1000 bed-days (IBD)] due to carbapenem-resistant Klebsiella pneumoniae (CRKP), carbapenem-resistant Pseudomonas aeruginosa (CRPA), carbapenem-resistant Acinetobacter baumannii (CRAB) and total carbapenem-resistant Gram-negative bacteria (CRGNB) in an endemic intensive care unit (ICU) during the subsequent year (December 2016–December 2017) following the observational period. Methods: A 52-month observational period (August 2012–November 2016) was used. Two forecasting models, including a simple seasonal model for CRGNB, CRKP and CRPA and Winters’ additive model for CRAB infections, were applied. Results: The models predicted the highest infection rates for CRKP, CRAB and CRGNB in January and September 2017 (23.8/23.4, 24.6/28.5 and 46.8/46.7 IBD, respectively) and for CRPA in February and March 2017 (8.3 and 7.9, respectively). The highest observed rates for CRKP, CRAB and CRGNB were indeed in January and September 2017 (25.6/19.0, 34.2/23.8 and 59.8/42.8 IBD, respectively); and for CRPA in February and March of the same year (15.2 and 12.7, respectively). The increased rates may be associated with personnel’s annual work programme and behavioural factors. Conclusion: Forecasting models in endemic ICUs may assist in implementation strategies for infection control measures.

Introduction: The aim of this study was to compare the efficacy and safety of colistin sulfate (CS) with polymyxin B sulfate (PMB) in the treatment of pneumonia induced by carbapenem-resistant Gram-negative bacteria (CR-GNB)., Methodology: Patients diagnosed with pneumonia caused by CR-GNB and admitted to the intensive care unit (ICU) from January 2020 to September 2022 were enrolled in this study. The patients were divided into the CS group and the PMB group according to their medication regimens. Group-wise demographic data, clinical efficacy, prognosis, and adverse events were analyzed and compared., Results: A total of 120 patients (68 in the CS group and 52 in the PMB group) with pneumonia were included in the study. The majority of the pathogens were CR-Acinetobacter baumannii, followed by CR-Klebsiella pneumoniae, and CR-Pseudomonas aeruginosa. The clinical response rates in the CS and PMB groups after treatment were 62.0% and 65.4%, bacterial clearances were 44.0% and 36.5%, 28-day mortality rates were 16.0% and 13.5%, respectively; no significant differences between the two treatments were found. Nevertheless, the adverse effects were significantly less common in the CS group than in the PMB group, especially when treatments were administered intravenously., Conclusions: CS, a novel polymyxin E formulation, is as effective as PMB in treating pneumonia induced by CR-GNB while causing less side effects., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Di Liu, Fang Jie, Yongjie Ding, Hongping Qu, Dechang Chen, Jie Huang.)

Objectives: This study aimed to estimate the disease burden of BSIs caused by gram-negative bacteria (GNB-BSIs) in a Brazilian hospital from 2015 to 2019, measured in disability-adjusted life-years (DALYs)., Methods: A retrospective cohort study of adult patients with GNB-BSI was conducted from April 01, 2015 to March 31, 2019. This study was carried out in a 356-bed private hospital with a 68-bed medical intensive care unit located in Salvador, Brazil. Demographic and clinical data were collected through a review of medical records. DALYs were estimated using Monte Carlo Simulations, using life tables for Brazilians estimated for 2020 and the Global Burden of Diseases 2010 (GBD 2010)., Results: A total of 519 GNB-BSI episodes in 498 individuals were identified. The mean age was 59.92 ± 17.97 years, with 61.1% being male. The most common bacterial infections were Klebsiella pneumoniae and Escherichia coli (66.5%), whereas carbapenem-resistant gram-negative bacteria (CR-GNB) accounted for 32.7% of cases. The highest overall DALYs were observed in 2018 (752, 95% confidence interval [CI]: 520-1021 with Brazilian Life Tables and 782, 95% CI: 540-1062 with GBD 2010). Infections due to CR-GNB had the highest DALYs, particularly, in 2017, reaching 7050 (95% CI: 3200-12,150 with Brazilian Life Tables and 7350, 95% CI: 3350-12,700 with GBD 2010) DALYs per 1000 patient days and an estimated mortality rate of 40% per 1000 patient days., Conclusions: The persistently high DALYs associated with CR-GNB raise alarming concerns, potentially leading to over 300 deaths per 1000 patient days in the coming years. These findings underscore the urgency of addressing GNB-BSI as a significant public health issue in Brazil. These results are expected to provide helpful information for public health policymakers to prioritize interventions for infections due to antibiotic-resistant bacteria., Competing Interests: The authors have no competing interests to declare., (© 2024 The Author(s).)

Background/purposes: The continuously increasing carbapenem resistance within Enterobacterales and Pseudomonas poses a threat to public health, nevertheless, the molecular characteristics of which in southern China still remain limited. And carbapenemase identification is a key factor in effective early therapy of carbapenem-resistant bacteria infections. We aimed to determine the molecular characteristics of these pathogens and compare commercial combined disc tests (CDTs) with the modified carbapenem inactivation method (mCIM) and EDTA-CIM (eCIM) in detecting and distinguishing carbapenemases using whole genome sequencing (WGS)., Methods: A total of 78 Enterobacterales , 30 Pseudomonas were obtained from two tertiary hospitals in southern China. Susceptibility tests were conducted using an automated VITEK2 compact system with confirmation via the Kirby-Bauer method. The WGS was conducted on all clinical isolates and the molecular characteristics were analyzed by screening the whole genome sequences. CDTs with or without cloxacillin, mCIM, and eCIM, were performed and compared by taking WGS results as the benchmark., Results: A total of 103 carbapenem non-susceptible and 5 carbapenem susceptible bacteria were determined, with Klebsiella pneumoniae (42.7%), Pseudomonas aeruginosa (23.3%) and Escherichia coli (18.4%) being most prevalent. Carbapenemase genes were detected in 58 (56.3%) of the 103 carbapenem-non-susceptible clinical isolates, including 46 NDM, 6 KPC, 3 IMP, 1 IPM+VIM,1NDM+KPC, and 1 OXA-181. Carbapenemase-producing isolates were detected more frequently in Enterobacterales (76.3%). Among K. pneumoniae , the major sequence types were st307 and st11, while among E. coli and P. aeruginosa , the most prevalent ones were st410 and st242 respectively. For carbapenemase detection in Enterobacterales , the mCIM method achieved 100.00% (95% CI, 92.13-100.00%) sensitivity and 94.44% (70.63-99.71%) specificity (kappa, 0.96); for Pseudomonas , detection sensitivity was 100% (5.46-100.00%), and 100% (84.50-100.00%) specificity (kappa, 0.65). Commercial CDT carbapenemase detection sensitivity for Enterobacterales was 96.49% (86.84-99.39%), and 95.24% (74.13-99.75%) specificity (kappa, 0.90); for Pseudomonas , carbapenemase detection sensitivity was 100.00% (5.46-100.00%) and 37.93% (21.30-57.64%) specificity (kappa, 0.04). When cloxacillin testing was added, CDT specificity reached 84.61% (64.27-94.95%)., Conclusion: The molecular epidemiology of carbapenem-non-susceptible isolates from pediatric patients in Southern China exhibited distinctive characteristics. Both the mCIM-eCIM combination and CDT methods effectively detected and differentiated carbapenemases among Enterobacterales isolates, and the former performed better than CDT among Pseudomonas ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liang, Chen, Liang, Li, Cai, Lai, Zhong, Xie, Huang, Gao and Long.)

Donor-derived infections (DDIs) caused by carbapenem-resistant gram-negative bacteria (CR-GNB) in solid organ transplant recipients are potentially life-threatening. In this prospective study, we evaluated the incidence, factors associated with transmission, and the outcome of recipients with unexpected CR-GNB DDIs after the implementation of our local active surveillance system (LASS). LASS provides for early detection of unexpected donor CR-GNB infections, prophylaxis of recipients at high risk, and early diagnosis and treatment of DDIs. Whole genome sequencing confirmed DDI. Among 791 recipients, 38 (4.8%) were at high risk of unexpected CR-GNB DDI: 25 for carbapenem-resistant Enterobacterales (CRE) and 13 for carbapenem-resistant Acinetobacter baumannii (CRAB). Transmission did not occur in 27 (71%) cases, whereas DDIs occurred in 9 of 25 of CRE and 2 of 13 of CRAB cases. Incidence of CR-GNB DDI was 1.4%. Recipients of organs with CR-GNB-positive preservation fluid and liver recipients from a donor with CRE infection were at the highest risk of DDI. There was no difference in length of hospital stay or survival in patients with and without CR-GNB DDI. Our LASS contains transmission and mitigates the negative impacts of CR-GNB DDI. Under well-defined conditions, organs from donors with CR-GNB may be considered after a thorough evaluation of the risk/benefit profile., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

To investigate the association between adjunctive nebulized colistin and treatment outcomes in critically ill patients with nosocomial carbapenem-resistant Gram-negative bacterial (CR-GNB) pneumonia. This retrospective, multi-centre, cohort study included individuals admitted to the intensive care unit with nosocomial pneumonia caused by colistin-susceptible CR-GNB. Enrolled patients were divided into groups with/without nebulized colistin as adjunct to at least one effective intravenous antibiotic. Propensity score matching was performed in the original cohort (model 1) and a time-window bias-adjusted cohort (model 2). The association between adjunctive nebulized colistin and treatment outcomes was analysed. In total, 181 and 326 patients treated with and without nebulized colistin, respectively, were enrolled for analysis. The day 14 clinical failure rate and mortality rate were 41.4% (75/181) versus 46% (150/326), and 14.9% (27/181) versus 21.8% (71/326), respectively. In the propensity score-matching analysis, patients with nebulized colistin had lower day 14 clinical failure rates (model 1: 41% (68/166) versus 54.2% (90/166), p 0.016; model 2: 35.3% (41/116) versus 56.9% (66/116), p 0.001). On multivariate analysis, nebulized colistin was an independent factor associated with fewer day 14 clinical failures (model 1: adjusted odds ratio (aOR) 0.59, 95% CI 0.37–0.92; model 2: aOR 0.37, 95% CI 0.21–0.65). Nebulized colistin was not associated independently with a lower 14-day mortality rate in the time-dependent analysis in both models 1 and 2. Adjunctive nebulized colistin was associated with lower day 14 clinical failure rate, but not lower 14-day mortality rate, in critically ill patients with nosocomial pneumonia caused by colistin-susceptible CR-GNB. [ABSTRACT FROM AUTHOR]

Infection is the leading cause of complications and deaths after burns. However, the difference in infection patterns between the burn intensive care unit (BICU) and burn common wards (BCW) have not been clearly investigated. The present study aimed to compare the infection profile, antimicrobial resistance, and their changing patterns in burn patients in BICU and BCW. Clinical samples were analyzed between January 1, 2011, and December 31, 2019, in the Institute of Burn Research in Southwest China. The patient information, pathogen distribution, sources, and antimicrobial resistance were retrospectively collected. A total of 3457 and 4219 strains were detected in BICU and BCW, respectively. Wound secretions accounted for 86.6% and 44.9% in BCW and BICU, respectively. Compared with samples in BCW, samples in BICU had more fungi (11.8% vs. 8.1%), more Gram-negative bacteria (60.0% vs. 50.8%), and less Gram-positive bacteria (28.2% vs. 41.1%). Acinetobacter baumannii were the most common pathogen in BICU, compared with Staphylococcus aureus in BCW. S. aureus was the most frequent pathogen in wound secretions and tissues from both BICU and BCW. However, A. baumannii were the first in blood, sputum, and catheter samples from BICU. Overall, the multidrug-resistance (MDR) rate was higher in BICU than in BCW. However, the gap between BICU and BCW gradually shortened from 2011 to 2019. The prevalence of MDR A. baumannii and Klebsiella pneumonia significantly increased, especially in BCW. Furthermore, Carbapenem resistance among K. pneumoniae significantly increased in BICU (4.5% in 2011 vs. 40% in 2019) and BCW (0 in 2011 vs. 40% in 2019). However, the percentage of MDR P. aeruginosa sharply dropped from 85.7% to 24.5% in BICU. The incidence of MRSA was significantly higher in BICU than in BCW (94.2% vs. 71.0%) and stayed at a high level in BICU (89.5% to 96.3%). C. tropicalis and C. albicans were the two most frequent fungi. No resistance to Amphotericin B was detected. Our study shows that the infection profile is different between BICU and BCW, and multidrug resistance is more serious in BICU than BCW. Therefore, different infection-control strategies should be emphasized in different burn populations.

Background Short-term readmission is an important outcome reflecting the poor trajectory of sepsis survivors. The aim of this study was to identify the major risk factors for 30-day readmission among patients with gram-negative bacteremia. Methods This was a retrospective cohort study including all consecutive adults hospitalized in the medical departments in a referral hospital in Israel with gram-negative bacteremia between 2011 and 2020, who were discharged alive. Predictors for 30-day readmission were investigated, considering death after discharge as a competing event. Cephalosporin resistance was our predictor of interest. Subdistribution hazard ratios (HRs) of the cumulative incidence function were investigated using the Fine and Gray multivariable competing-risk regression model. The prediction models were cross-validated using the k-fold method. Results Among 2196 patients surviving hospitalization with gram-negative bacteremia, the mean age was 70 ± 16 years and 432 (19.6%) were readmitted within 30 days. Variables associated with readmission hazards were Arab ethnicity, active malignancy, conditions requiring immunosuppression, anxiolytics or hypnotics, anticoagulant or antiplatelet therapy, discharge with a nasogastric tube, higher predischarge heart rate, duration of antibiotic therapy during hospitalization, and bacteremia caused by cephalosporin-resistant bacteria (HR, 1.23 [95% confidence interval {CI},.99–1.52]). The area under the receiver operating characteristic curve for this model was 75.5% (95% CI, 71.3%–79.1%). In secondary models, cephalosporin resistance, inappropriate empirical antibiotic treatment, and lower predischarge albumin were significantly associated with readmission. Conclusions Thirty-day readmissions among patients with gram-negative bacteremia surviving the index admission were high. Readmission was related to comorbidities and infections caused by multidrug-resistant infections. Main point: Among 2196 adults surviving hospitalization with gram-negative bacteremia, 432 (19.6%) were rehospitalized within 30 days. Comorbidities, inappropriate empirical antibiotic treatment, bacteremia caused by cephalosporin-resistant bacteria, predischarge heart rate, and albumin were associated with readmissions. [ABSTRACT FROM AUTHOR]

Infection is the leading cause of complications and deaths after burns. However, the difference in infection patterns between the burn intensive care unit (BICU) and burn common wards (BCW) have not been clearly investigated. The present study aimed to compare the infection profile, antimicrobial resistance, and their changing patterns in burn patients in BICU and BCW. Clinical samples were analyzed between January 1, 2011, and December 31, 2019, in the Institute of Burn Research in Southwest China. The patient information, pathogen distribution, sources, and antimicrobial resistance were retrospectively collected. A total of 3457 and 4219 strains were detected in BICU and BCW, respectively. Wound secretions accounted for 86.6% and 44.9% in BCW and BICU, respectively. Compared with samples in BCW, samples in BICU had more fungi (11.8% vs. 8.1%), more Gram-negative bacteria (60.0% vs. 50.8%), and less Gram-positive bacteria (28.2% vs. 41.1%). Acinetobacter baumannii were the most common pathogen in BICU, compared with Staphylococcus aureus in BCW. S. aureus was the most frequent pathogen in wound secretions and tissues from both BICU and BCW. However, A. baumannii were the first in blood, sputum, and catheter samples from BICU. Overall, the multidrug-resistance (MDR) rate was higher in BICU than in BCW. However, the gap between BICU and BCW gradually shortened from 2011 to 2019. The prevalence of MDR A. baumannii and Klebsiella pneumonia significantly increased, especially in BCW. Furthermore, Carbapenem resistance among K. pneumoniae significantly increased in BICU (4.5% in 2011 vs. 40% in 2019) and BCW (0 in 2011 vs. 40% in 2019). However, the percentage of MDR P. aeruginosa sharply dropped from 85.7% to 24.5% in BICU. The incidence of MRSA was significantly higher in BICU than in BCW (94.2% vs. 71.0%) and stayed at a high level in BICU (89.5% to 96.3%). C. tropicalis and C. albicans were the two most frequent fungi. No resistance to Amphotericin B was detected. Our study shows that the infection profile is different between BICU and BCW, and multidrug resistance is more serious in BICU than BCW. Therefore, different infection-control strategies should be emphasized in different burn populations. [ABSTRACT FROM AUTHOR]