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To assess the efficacy and safety of colistin sulfate in treating infections caused by carbapenem-resistant organisms (CRO) and to analyze potential factors impacting its effectiveness. Methods: In this retrospective study, medical records of CRO-infected patients from June 2020 to June 2023 were analyzed, divided into effective and ineffective treatment groups, and compared for clinical outcomes and adverse reactions. Multifactorial logistic regression and ROC curve analysis were used to identify influencing factors. Results: The study included 226 patients, with 124 in the effective treatment group and 102 in the ineffective group. A total of 293 CRO strains were cultured. The clinical efficacy rate of colistin sulfate was 54.87%, the microbiological efficacy rate 46.46%, and the hospital mortality rate 20.80%, with nephrotoxicity observed in 11.50% of patients. Multifactorial analysis identified APACHE II scores and vasoactive drug use as independent predictors of ineffective treatment, while treatment duration and albumin levels predicted effective treatment. ROC analysis indicated that albumin levels > 34 g/L, APACHE II scores < 13, and treatment duration > 10 days correlated with better clinical efficacy. Conclusion: Colistin sulfate is both safe and effective in clinical settings. Factors such as treatment duration, albumin levels, APACHE II scores, and vasoactive drug use independently affect its clinical efficacy, providing valuable guidance for its informed clinical application. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant organisms (CROs) are a significant public health threat globally, particularly in countries like India with high antibiotic resistance rates. The current study investigates the prevalence of CROs, detects resistance mechanisms using phenotypic methods and assesses the efficacy of newer antibiotics against CROs. A prospective study conducted at a tertiary care hospital in India during 2021–23. Clinical specimens were processed and bacterial identification was performed using MALDI-TOF mass spectrometry followed by antimicrobial susceptibility testing using CLSI guidelines against a plethora of newer antibiotics for CROs. Carbapenemase production was detected using phenotypic methods, and the presence of the mcr-1 gene was assessed by real-time PCR. During the study period, predominantly (70 %) Gram-negative bacteria were isolated; amongst which 5692 strains were carbapenem-resistant, wherein resistance to different carbapenems ranged from 34.1% to 79 %. Majority of the carbapenemase producers were metallo-β-lactamases (MBL) producers (75 %). Colistin resistance was noted in 5.4 % of selected carbapenem-resistant isolates. Among newer antibiotics, cefiderocol demonstrated the lowest resistance rates (0–14 %), while resistance to newer β-lactam/β-lactamase inhibitor combinations was very high in carbapenem-resistant isolates. Fosfomycin, minocycline and tigecycline, each showing variable efficacy depending on the site of infection. Moreover, newer β-lactam/β-lactamase inhibitor combinations offer restricted benefits due to widespread prevalence of MBL in the region. The escalating prevalence of CROs in India underscores the urgency for alternative treatment options beyond colistin. Hence, highlighting the critical importance of developing effective strategies to combat carbapenem resistance. [ABSTRACT FROM AUTHOR]

ABSTRACT: Objectives: The objective is to explore the correlation between rectal swab culture and the overall 30-d survival of hematologic patients diagnosed with carbapenem-resistant organism (CRO) bloodstream infection. Methods: A total of 434 haematological patients who were complicated with Gram-negative bacilli (GNB) bloodstream infections (BSIs) caused by Gram-negative bacteria between January 2020 and December 2021 were included in our retrospective study. Based on their drug susceptibility results, we classified patients into CRO BSIs and non-CRO BSIs cases. Through group comparison, to uncover the correlation between the positive screening of rectal swabs and reducing the mortality of CRO BSI in patients with haematological diseases. Results: Among the 434 cases of Gram-negative bacteria bloodstream infection, 96 were identified as carbapenem-resistant bloodstream infection, which consisted of 57 cases of carbapenem-resistant Klebsiella pneumoniae (CR-KP), 19 cases of carbapenem-resistant Pseudomonas aeruginosa (CR-PA), 11 cases of carbapenem-resistant Escherichia coli (CR-CO), 5 cases of carbapenem-resistant Acinetobacter baumannii (CR-AB), and 4 cases of other Enterobacteriaceae. Before the onset of CRO bloodstream infection, rectal swab cultures were conducted on 36 patients, and the positive result rate was 75.0% (27/36), with 20 cases of CR-KP, 6 cases of CR-CO, and one case of carbapenem-resistant Enterobacter cloacae. It was observed that the rectal and blood cultures had matching outcomes in 75.0% of cases. The mortality rate within 30 d for CRO BSIs was 53.1% (51/96), while for carbapenem-resistant Enterobacteriaceae (CRE) BSIs it was 62.5% (45/72). Univariate analysis showed that 30-d mortality was significantly reduced when there were positive rectal culture results preceding bloodstream infection (P < 0.001), as well as preemptive anti-infection treatment (P < 0.001). Multivariate analysis demonstrated that preemptive adjustment to an effective antibiotic regimen, guided by positive rectal culture results, had a significant effect on decreasing 30-d mortality following CRO BSIs (P = 0.002). Furthermore, for the management of CRE BSIs, antibiotic treatments utilising ceftazidime/avibactam (CAV/AVI) may be more beneficial compared to those that use tigecycline (TGC) or polymyxin (PMB). Conclusion: CRO BSI, especially CRE BSI, can be life-threatening for those with haematological diseases. Utilising rectal culture can effectively identify CRO strains with high sensitivity and specificity. Adjusting antibiotic treatment based on the preemptive positive rectal culture results may significantly decrease 30-d mortality rates for haematological patients with CRO BSIs.

Abstract The widespread occurrence of carbapenem-resistant organisms has garnered significant public attention. Arthropods, including flies, are important vectors of multidrug-resistant bacteria. In this study, we reported the simultaneous carriage of four carbapenem-resistant isolates from different species, namely, Escherichia coli (E. coli), Providencia manganoxydans (P. manganoxydan), Myroides odoratimimus (M. odoratimimus) and Proteus mirabilis (P. mirabilis), from a single fly in China. These isolates were characterized through antimicrobial susceptibility testing, conjugation assays, whole-genome sequencing, and bioinformatics analysis. M. odoratimimus showed intrinsic resistance to carbapenems. The mechanisms of carbapenem resistance in E. coli, P. manganoxydans, and P. mirabilis were due to the production of NDM-5, NDM-1 and NDM-1, respectively. Genetic context of the bla NDM genes in these three isolates varied. The bla NDM-5 gene in E. coli was located on an IncHI2/HI2A multidrug-resistant plasmid, which was conjugatively transferable. The bla NDM-1 gene in P. mirabilis resided on the pPM14-NDM_123k-like nonconjugative plasmid. The bla NDM-1 gene in P. manganoxydans was found in a nonconjugatively transferable, multidrug-resistant region. The results of this study enhance our understanding of the dissemination of carbapenem-resistant organisms and suggest the need for a more comprehensive approach to antibiotic resistance research encompassing humans, animals, and the environment.

Objectives. This study aimed to evaluate and compare the performance of different assays for antimicrobial susceptibility testing (AST) and minimum inhibitory concentration (MIC) determination for reserve antibiotics in carbapenem-resistant Enterobacterales (CREs), Pseudomonas aeruginosa (CRPAs), and Acinetobacter baumannii (CRABs). Methods. An analysis was conducted on 100 consecutive isolates: 50 CREs, 35 CRPAs, and 15 CRABs. Sensititre broth microdilution was used as a reference standard to evaluate the performance of VITEK 2 card AST-XN24 (bioMérieux), the respective gradient tests (bioMérieux), and UMIC colistin broth microdilution test strips (Bruker Daltonics). Errors, essential agreement (EA), and categorical agreement of MICs for colistin (COL), meropenem–vaborbactam (MVB), imipenem–relebactam (IRL), and eravacycline (ERV) were assessed. Results. The agreement between both of the COL broth microdilution (BMD) methods was perfect (100/100). The gradient test and VITEK 2 analysis yielded comparable EA rates (92/100 and 72/79, respectively), with the latter not registering any very major errors (VMEs). The MVB gradient test achieved EA in 66 of 85 isolates and VITEK 2 in 70/85. For IRL, EA was reached in 69 and 64 of 85 cases by gradient test and VITEK 2 analysis, respectively. The ERV gradient test yielded false results in nearly all (12/15) CRABs but achieved EA in 46 of 50 CREs. The VITEK system recorded EA for ERV in 60 of 65 isolates. Conclusions. We observed substantial variability in the measured MICs between BMD and the alternative methods. In only a few constellations, VITEK 2 or gradient tests could substitute the reference method. BMD is the method of choice for COL analysis, with VITEK 2 representing an alternative method for CRPA testing. Alternative methods for MVB did not provide reliable results, except for Enterobacterales, when tested with the gradient test. However, resistant results need to be confirmed by BMD. Only BMD can be used for IRL MIC determination. VITEK 2 was mostly accurate in measuring ERV MICs, while the corresponding gradient test yielded reliable results exclusively in CREs. It is essential that laboratories are aware of which testing method provides reliable results for each combination of microorganisms and reserve antibiotics.

ABSTRACT: Background: To investigate the clinical distribution and changing trend of antibiotic resistance profiles of multidrug-resistant organisms (MDROs), a retrospective study was undertaken. Methods: The characteristics of MDROs isolated from 2016 to March 2023 were retrospectively analysed. The detection rate of these MDROs was compared prior to COVID-19 (Period 1, 2016–2019), during the COVID-19 pandemic with restrictions (Period 2, 2020–2022), and after the end of zero-policy (Period 3, Jan-March, 2023). Antibiotic-resistant genes were detected. Results: The overall detection rates of CRPA, CRAB, CREC, CRKP, MRSA, and VREfm were 22.6%, 22.6%, 1.3%, 4.0%, 19.5%, and 3.1%, respectively. The detection rate of CRAB was significantly lower in Period 2 and 3 compared with Period 1 (P < 0.0001). The detection rate of CRPA and VREfm was significantly increased in Period 3 compared with Period 1 and 2 (P < 0.0001). The resistance rate to ticarcillin/clavulanic acid (TIM) and piperacillin/tazobactam (TZP) has gradually increased in CRPA since 2018. NDM and KPC were the most common carbapenemase genes identified in CREC (60.0%) and CRKP isolates (47.8%), respectively. All the 10 VREfm isolates carried the vanA gene. Conclusions: The detection rate of CRAB has decreased since 2018, but a significantly increased prevalence of CRPA and VREfm was seen after the end of zero-policy. An increasing resistance rate to TIM and TZP was seen in CRPA. NDM, KPC, and vanA were the common genes harboured by CREC, CRKP, and VREfm, respectively. Ongoing surveillance after the COVID-19 era is suggested.

The widespread occurrence of carbapenem-resistant organisms has garnered significant public attention. Arthropods, including flies, are important vectors of multidrug-resistant bacteria. In this study, we reported the simultaneous carriage of four carbapenem-resistant isolates from different species, namely, Escherichia coli (E. coli), Providencia manganoxydans (P. manganoxydan), Myroides odoratimimus (M. odoratimimus) and Proteus mirabilis (P. mirabilis), from a single fly in China. These isolates were characterized through antimicrobial susceptibility testing, conjugation assays, whole-genome sequencing, and bioinformatics analysis. M. odoratimimus showed intrinsic resistance to carbapenems. The mechanisms of carbapenem resistance in E. coli, P. manganoxydans, and P. mirabilis were due to the production of NDM-5, NDM-1 and NDM-1, respectively. Genetic context of the blaNDM genes in these three isolates varied. The blaNDM-5 gene in E. coli was located on an IncHI2/HI2A multidrug-resistant plasmid, which was conjugatively transferable. The blaNDM-1 gene in P. mirabilis resided on the pPM14-NDM_123k-like nonconjugative plasmid. The blaNDM-1 gene in P. manganoxydans was found in a nonconjugatively transferable, multidrug-resistant region. The results of this study enhance our understanding of the dissemination of carbapenem-resistant organisms and suggest the need for a more comprehensive approach to antibiotic resistance research encompassing humans, animals, and the environment. [ABSTRACT FROM AUTHOR]

Abstract Background To study the efficacy and nephrotoxicity of polymyxin B in the treatment of elderly patients with carbapenem-resistant organism (CRO) infection. Methods The clinical and microbiological data of patients with CRO-infected sepsis treated with polymyxin B were retrospectively analyzed. The effective rate, bacterial clearance, incidence and recovery rate of acute renal injury (AKI) and prognosis-related indicators in AKI at different stages were compared. Results The effective rate of 215 elderly patients with CRO infection treated with polymyxin was 50.7%. The total bacterial clearance rate was 44.2%, the total incidence of AKI was 37.2%, the recovery rate of AKI was 35%, and the incidence range of polymyxin B-related AKI was 10.2–37.2%. Logistic multivariate regression analysis showed that the predictors of AKI in elderly patients were high APACHE II score, long duration of polymyxin, chronic renal insufficiency and ineffective outcome; the ROC curve showed that the cutoff value for predicting AKI was a serum creatinine concentration of 73 mmol/L before polymyxin B use, and the AUC was 0.931. Conclusions Rational use of polymyxin B is safe and effective in elderly patients with CRO infection, and its effective outcome can improve the recovery rate of AKI.

Background: To study the efficacy and nephrotoxicity of polymyxin B in the treatment of elderly patients with carbapenem-resistant organism (CRO) infection. Methods: The clinical and microbiological data of patients with CRO-infected sepsis treated with polymyxin B were retrospectively analyzed. The effective rate, bacterial clearance, incidence and recovery rate of acute renal injury (AKI) and prognosis-related indicators in AKI at different stages were compared. Results: The effective rate of 215 elderly patients with CRO infection treated with polymyxin was 50.7%. The total bacterial clearance rate was 44.2%, the total incidence of AKI was 37.2%, the recovery rate of AKI was 35%, and the incidence range of polymyxin B-related AKI was 10.2–37.2%. Logistic multivariate regression analysis showed that the predictors of AKI in elderly patients were high APACHE II score, long duration of polymyxin, chronic renal insufficiency and ineffective outcome; the ROC curve showed that the cutoff value for predicting AKI was a serum creatinine concentration of 73 mmol/L before polymyxin B use, and the AUC was 0.931. Conclusions: Rational use of polymyxin B is safe and effective in elderly patients with CRO infection, and its effective outcome can improve the recovery rate of AKI. [ABSTRACT FROM AUTHOR]

The acute crisis of carbapenem resistance impedes the empirical use of carbapenems in medical emergencies, especially, bloodstream infections. Carbapenemase-producing carbapenem-resistant organisms (CP-CROs) attribute high case-fatality, necessitating rapid diagnostics to initiate early targeted antibiotics. Expensive diagnostics are the major driver of antibiotic misuse, neglecting evidence-based treatment in India. One in-house molecular diagnostics assay was customized for rapid detection of CP-CROs using positive blood-culture (BC) broths at a low-cost. The assay was validated using a known-set of isolates and evaluated on positive BC broths. DNA was extracted from positive BC broths using a modified alkali-wash/heat-lysis method. One end-point multiplex-PCR was customized targeting five carbapenemases (KPC, NDM, VIM, OXA-48-, and OXA-23-type) with 16S-rDNA as internal extraction control. Carbapenem resistance due to other carbapenemases, efflux-pump activity, and loss of porins was not under the scope of the assay. Promising analytical performances (sensitivity and specificity, >90%; kappa = 0.87), encouraged to assess diagnostic value, qualified the assay for the WHO minimal requirements (both≥95%) for a multiplex-PCR. Higher LR+ (>10) and lower LR− (<0.1) indicate a good diagnostic tool for ruling in or ruling out CRO bloodstream infections. Inclusion of OXA-23-type improved assay positivity. Multiple carbapenemases were detected in>30% of samples. Good concordance was found (kappa = 0.91) with twenty-six discrepant results. The results were available in 3 hours. The running cost of the assay was US$10 per sample. Fast and reliable detection of carbapenemase(s) allows clinicians and infection-control practitioners to execute early-directed therapy and containment measures. This convenient approach facilitates implementing the assay in resource-limited healthcare settings. [ABSTRACT FROM AUTHOR]

Abstract Background Polymyxin B is the first-line therapy for Carbapenem-resistant organism (CRO) nosocomial pneumonia. However, clinical data for its pharmacokinetic/pharmacodynamic (PK/PD) relationship are limited. This study aimed to investigate the relationship between polymyxin B exposure and efficacy for the treatment of CRO pneumonia in critically ill patients, and to optimize the individual dosing regimens. Methods Patients treated with polymyxin B for CRO pneumonia were enrolled. Blood samples were assayed using a validated high-performance liquid chromatography-tandem mass spectrometry method. Population PK analysis and Monte Carlo simulation were performed using Phoenix NLME software. Logistic regression analyses and receiver operating characteristic (ROC) curve were employed to identify the significant predictors and PK/PD indices of polymyxin B efficacy. Results A total of 105 patients were included, and the population PK model was developed based on 295 plasma concentrations. AUCss,24 h/MIC (AOR = 0.97, 95% CI 0.95–0.99, p = 0.009), daily dose (AOR = 0.98, 95% CI 0.97–0.99, p = 0.028), and combination of inhaled polymyxin B (AOR = 0.32, 95% CI 0.11–0.94, p = 0.039) were independent risk factors for polymyxin B efficacy. ROC curve showed that AUCss,24 h/MIC is the most predictive PK/PD index of polymyxin B for the treatment of nosocomial pneumonia caused by CRO, and the optimal cutoff point value was 66.9 in patients receiving combination therapy with another antimicrobial. Model-based simulation suggests that the maintaining daily dose of 75 and 100 mg Q12 h could achieve ≥ 90% PTA of this clinical target at MIC values ≤ 0.5 and 1 mg/L, respectively. For patients unable to achieve the target concentration by intravenous administration, adjunctive inhalation of polymyxin B would be beneficial. Conclusions For CRO pneumonia, daily dose of 75 and 100 mg Q12 h was recommended for clinical efficacy. Inhalation of polymyxin B is beneficial for patients who cannot achieve the target concentration by intravenous administration.

Background: Polymyxin B is the first-line therapy for Carbapenem-resistant organism (CRO) nosocomial pneumonia. However, clinical data for its pharmacokinetic/pharmacodynamic (PK/PD) relationship are limited. This study aimed to investigate the relationship between polymyxin B exposure and efficacy for the treatment of CRO pneumonia in critically ill patients, and to optimize the individual dosing regimens. Methods: Patients treated with polymyxin B for CRO pneumonia were enrolled. Blood samples were assayed using a validated high-performance liquid chromatography-tandem mass spectrometry method. Population PK analysis and Monte Carlo simulation were performed using Phoenix NLME software. Logistic regression analyses and receiver operating characteristic (ROC) curve were employed to identify the significant predictors and PK/PD indices of polymyxin B efficacy. Results: A total of 105 patients were included, and the population PK model was developed based on 295 plasma concentrations. AUCss,24 h/MIC (AOR = 0.97, 95% CI 0.95–0.99, p = 0.009), daily dose (AOR = 0.98, 95% CI 0.97–0.99, p = 0.028), and combination of inhaled polymyxin B (AOR = 0.32, 95% CI 0.11–0.94, p = 0.039) were independent risk factors for polymyxin B efficacy. ROC curve showed that AUCss,24 h/MIC is the most predictive PK/PD index of polymyxin B for the treatment of nosocomial pneumonia caused by CRO, and the optimal cutoff point value was 66.9 in patients receiving combination therapy with another antimicrobial. Model-based simulation suggests that the maintaining daily dose of 75 and 100 mg Q12 h could achieve ≥ 90% PTA of this clinical target at MIC values ≤ 0.5 and 1 mg/L, respectively. For patients unable to achieve the target concentration by intravenous administration, adjunctive inhalation of polymyxin B would be beneficial. Conclusions: For CRO pneumonia, daily dose of 75 and 100 mg Q12 h was recommended for clinical efficacy. Inhalation of polymyxin B is beneficial for patients who cannot achieve the target concentration by intravenous administration. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to assess the current incidence and risk factors for polymyxin B-associated acute kidney injury (AKI) in Chinese hospitals for a more effective clinical use for polymyxin B. Methods: This multicenter, retrospective cohort study included patients from 14 Chinese teaching hospitals who received polymyxin B therapy. Univariate and multivariate logistic regression models were used to determine the factors associated with polymyxin B-associated incident AKI. Furthermore, a multivariate logistic regression model was used to identify the independent risk factors for AKI. Results: A total of 251 patients were included in the analysis. The overall incidence of AKI was 33.5%. A multivariate logistic regression model identified the loading dose (hazard ratio (HR), 1.84; 95% confidence interval (CI), 1.01–3.38; P = 0.0491) and the use of two or more nephrotoxic drugs (HR, 3.56; 95% CI, 1.55–8.18; P = 0.0029) as independent risk factors for the occurrence of AKI. Meanwhile, the estimated glomerular filtration rate had a protective effect (HR, 0.99; 95% CI, 0.98–0.99; P = 0.0006) on the occurrence of AKI. The daily dose, cumulative dose, and treatment duration of polymyxin B did not affect the occurrence of AKI. Conclusions: The use of polymyxin B loading doses and the combined use of multiple nephrotoxic drugs are independent risk factors for polymyxin B-associated AKI. The severity of AKI may be higher in patients with elevated baseline creatinine levels.

Carbapenem-resistant organism (CRO) are defined as gram-negative bacteria. The lack of safe and effective antibiotics has led to an increase in incidence rate. The purpose of this study is to establish and determine a risk nomogram to predict CRO infection in hospitalized patients. Hospitalized patients' information were collected from the electronic medical record system of hospital between January 2019 and December 2022. Based on the inclusion and exclusion criteria, we identified 131390 inpatients who met the criteria for this study. For the training cohort, the area under the curves (AUC) for predicting the CRO infection was 0.935. For the validation cohort, the AUC for predicting the CRO infection was 0.937. We have developed the first novel nomogram to predict CRO infection in hospitalized patients, which is reliable and high-performance. The nomogram performs well among hospitalized patients and has good predictive ability. [ABSTRACT FROM AUTHOR]

Objectives: Patients with acute‐on‐chronic liver failure (ACLF) have a high risk of infection after liver transplantation (LT). In this study, we aimed to evaluate the prevalence of early post‐LT infection (within one month after LT) in recipients with ACLF, and to compare the survival rate between patients with or without post‐LT infection. Methods: Patients with ACLF who underwent LT between January 2015 and December 2017 were retrospectively included. Characteristics of the patients, prevalence, site and pathogen of post‐LT infection, and its risk factors were evaluated. Results: A total of 62 patients with ACLF developed bacterial or fungal infection after LT. The 30‐day, 90‐day, and 1‐year survival rates in the infected group were found to be significantly lower than those in the non‐infected group (67.7% vs 98.5%, 64.5% vs 97.7%, and 48.4% vs 95.4%; all P < 0.001). The most common pathogens involved were carbapenem‐resistant gram‐negative organisms, including Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter lwoffi. Multivariate analysis demonstrated that reoperation and length of intensive care unit stay were independently associated with post‐LT infection. In addition, living donor LT and early allograft dysfunction were independently associated with 30‐day all‐cause mortality, whereas red blood cell transfusion and post‐LT infection were independently associated with all‐cause 30‐day and 90‐day mortality after LT. Conclusions: Early infection after LT is a major prognostic factor in patients with ACLF. Constant vigilance for the risk factors of early infection after LT is needed for timely diagnosis and prompt intervention. [ABSTRACT FROM AUTHOR]

Introduction: Infections caused by Gram-negative bacteria, in particular carbapenem-resistant organisms (CRO), pose a great threat to liver transplant (LT) recipients. Understanding the risk factors for Gram-negative and CRO infections and the drug resistance of corresponding bacteria will help guide the prevention and treatment of these infections. Methods: Data on the composition, distribution and drug resistance of Gram-negative bacteria and CRO among LT recipients were collected. The risk factors for Gram-negative and CRO infections were identified via univariate and multivariate analysis. Results: A total of 45 episodes of Gram-negative infection, including 20 episodes of CRO infection, occurred in 19.9% (27/136) of LT recipients. Klebsiella pneumoniae was the dominant pathogenic bacteria (14/45; 31.1%). The most common site of infection was the abdominal cavity/bile duct (11/27; 40.7%). Eleven (8.1%) patients died within 2 months after LT, and two deaths were related to Gram-negative infection. Gram-negative bacteria were relatively sensitive to tigecycline and polymyxin B, with resistance of 26.7 and 11.1%, respectively. CRO had lower resistance to ceftazidime/avibactam (45.5%) and polymyxin B (10%). A univariate analysis showed that male sex, infection within 2 months prior to LT, duration of surgery ≥ 400 min, reoperation, indwelling urethral catheter use ≥ 3 days and elevated alanine aminotransferase on day 1 post-LT were associated with Gram-negative infection. Multivariate logistic regression analysis revealed that infection within 2 months prior to LT [odds ratio (OR) = 4.426, 95%CI: 1.634–11.99, P = 0.003], duration of surgery ≥ 400 min [OR = 3.047, 95%CI: 1.194–7.773, P = 0.02] and indwelling urethral catheter use ≥ 3 days [OR = 5.728, 95%CI: 1.226–26.763, P = 0.026] were independent risk factors for Gram-negative infection after LT, and that only carbapenem use ≥ 3 days within 15 days prior to infection [OR = 14, 95%CI: 1.862–105.268, P = 0.01] was related to the occurrence of CRO infections. Conclusion: The incidence of Gram-negative and CRO infections was high in the early post-LT period. The most common infection site was the abdominal cavity/bile duct, and the dominant pathogen was K. pneumoniae. Patients with infections within 2 months prior to LT, prolonged surgery time or delayed urethral catheter removal were prone to Gram-negative infection. Carbapenem exposure was correlated with CRO infections. [ABSTRACT FROM AUTHOR]

IntroductionIt is not clear whether polymyxin B/tigecycline (PMB/TGC) combination is better than PMB or TGC alone in the treatment of hospital-acquired pneumonia (HAP) caused by carbapenem-resistant organisms (CROs).MethodsWe conducted a multicenter, retrospective cohort study in patients with HAP caused by CROs. The primary outcome was 28-day mortality, and the secondary outcomes included clinical success and the incidence of acute kidney injury (AKI). Multivariate Cox regression analysis was performed to examine the relationship between antimicrobial treatments and 28-day mortality by adjusting other potential confounding factors.ResultsA total of 364 eligible patients were included in the final analysis, i.e., 99 in the PMB group, 173 in the TGC group, and 92 in the PMB/TGC combination group. The 28-day mortality rate was 28.3% (28/99) in the PMB group, 39.3% (68/173) in the TGC group, and 48.9% (45/92) in the PMB/TGC combination group (p = 0.014). The multivariate Cox regression model showed that there was a statistically significant lower risk of 28-day mortality among participants in the PMB group when compared with the PMB/TGC combination group [hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.31–0.81, p = 0.004] and that participants in the TGC group had a lower risk of 28-day mortality than in the PMB/TGC combination group but without statistical significance. The incidence of AKI in the PMB group (52.5%) and the PMB/TGC combination group (53.3%) was significantly higher than that in the TGC group (33.5%, p = 0.001).ConclusionThe appropriate PMB/TGC combination was not superior to appropriate PMB therapy in the treatment of HAP caused by carbapenem-resistant Enterobacteriaceae/carbapenem-resistant Acinetobacter baumannii (CRE/CRAB) in terms of 28-day mortality.

• Polymyxin-associated nephrotoxicity remains a major concern in the clinical setting • The overall incidence of AKI was 33.5% among 14 Chinese teaching hospitals • Loading dose and use of multiple nephrotoxic drugs are independent risk factors for AKI • Severity of AKI may be higher in patients with elevated baseline creatinine levels This study aimed to assess the current incidence and risk factors for polymyxin B-associated acute kidney injury (AKI) in Chinese hospitals for a more effective clinical use for polymyxin B. This multicenter, retrospective cohort study included patients from 14 Chinese teaching hospitals who received polymyxin B therapy. Univariate and multivariate logistic regression models were used to determine the factors associated with polymyxin B-associated incident AKI. Furthermore, a multivariate logistic regression model was used to identify the independent risk factors for AKI. A total of 251 patients were included in the analysis. The overall incidence of AKI was 33.5%. A multivariate logistic regression model identified the loading dose (hazard ratio (HR), 1.84; 95% confidence interval (CI), 1.01–3.38; P = 0.0491) and the use of two or more nephrotoxic drugs (HR, 3.56; 95% CI, 1.55–8.18; P = 0.0029) as independent risk factors for the occurrence of AKI. Meanwhile, the estimated glomerular filtration rate had a protective effect (HR, 0.99; 95% CI, 0.98–0.99; P = 0.0006) on the occurrence of AKI. The daily dose, cumulative dose, and treatment duration of polymyxin B did not affect the occurrence of AKI. The use of polymyxin B loading doses and the combined use of multiple nephrotoxic drugs are independent risk factors for polymyxin B-associated AKI. The severity of AKI may be higher in patients with elevated baseline creatinine levels. [ABSTRACT FROM AUTHOR]

Background: To investigate the clinical distribution and changing trend of antibiotic resistance profiles of multidrug-resistant organisms (MDROs), a retrospective study was undertaken., Methods: The characteristics of MDROs isolated from 2016 to March 2023 were retrospectively analysed. The detection rate of these MDROs was compared prior to COVID-19 (Period 1, 2016-2019), during the COVID-19 pandemic with restrictions (Period 2, 2020-2022), and after the end of zero-policy (Period 3, Jan-March, 2023). Antibiotic-resistant genes were detected., Results: The overall detection rates of CRPA, CRAB, CREC, CRKP, MRSA, and VREfm were 22.6%, 22.6%, 1.3%, 4.0%, 19.5%, and 3.1%, respectively. The detection rate of CRAB was significantly lower in Period 2 and 3 compared with Period 1 (P < 0.0001). The detection rate of CRPA and VREfm was significantly increased in Period 3 compared with Period 1 and 2 (P < 0.0001). The resistance rate to ticarcillin/clavulanic acid (TIM) and piperacillin/tazobactam (TZP) has gradually increased in CRPA since 2018. NDM and KPC were the most common carbapenemase genes identified in CREC (60.0%) and CRKP isolates (47.8%), respectively. All the 10 VREfm isolates carried the vanA gene., Conclusions: The detection rate of CRAB has decreased since 2018, but a significantly increased prevalence of CRPA and VREfm was seen after the end of zero-policy. An increasing resistance rate to TIM and TZP was seen in CRPA. NDM, KPC, and vanA were the common genes harboured by CREC, CRKP, and VREfm, respectively. Ongoing surveillance after the COVID-19 era is suggested., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: The objective is to explore the correlation between rectal swab culture and the overall 30-d survival of hematologic patients diagnosed with carbapenem-resistant organism (CRO) bloodstream infection., Methods: A total of 434 haematological patients who were complicated with Gram-negative bacilli (GNB) bloodstream infections (BSIs) caused by Gram-negative bacteria between January 2020 and December 2021 were included in our retrospective study. Based on their drug susceptibility results, we classified patients into CRO BSIs and non-CRO BSIs cases. Through group comparison, to uncover the correlation between the positive screening of rectal swabs and reducing the mortality of CRO BSI in patients with haematological diseases., Results: Among the 434 cases of Gram-negative bacteria bloodstream infection, 96 were identified as carbapenem-resistant bloodstream infection, which consisted of 57 cases of carbapenem-resistant Klebsiella pneumoniae (CR-KP), 19 cases of carbapenem-resistant Pseudomonas aeruginosa (CR-PA), 11 cases of carbapenem-resistant Escherichia coli (CR-CO), 5 cases of carbapenem-resistant Acinetobacter baumannii (CR-AB), and 4 cases of other Enterobacteriaceae. Before the onset of CRO bloodstream infection, rectal swab cultures were conducted on 36 patients, and the positive result rate was 75.0% (27/36), with 20 cases of CR-KP, 6 cases of CR-CO, and one case of carbapenem-resistant Enterobacter cloacae. It was observed that the rectal and blood cultures had matching outcomes in 75.0% of cases. The mortality rate within 30 d for CRO BSIs was 53.1% (51/96), while for carbapenem-resistant Enterobacteriaceae (CRE) BSIs it was 62.5% (45/72). Univariate analysis showed that 30-d mortality was significantly reduced when there were positive rectal culture results preceding bloodstream infection (P < 0.001), as well as preemptive anti-infection treatment (P < 0.001). Multivariate analysis demonstrated that preemptive adjustment to an effective antibiotic regimen, guided by positive rectal culture results, had a significant effect on decreasing 30-d mortality following CRO BSIs (P= 0.002). Furthermore, for the management of CRE BSIs, antibiotic treatments utilising ceftazidime/avibactam (CAV/AVI) may be more beneficial compared to those that use tigecycline (TGC) or polymyxin (PMB)., Conclusion: CRO BSI, especially CRE BSI, can be life-threatening for those with haematological diseases. Utilising rectal culture can effectively identify CRO strains with high sensitivity and specificity. Adjusting antibiotic treatment based on the preemptive positive rectal culture results may significantly decrease 30-d mortality rates for haematological patients with CRO BSIs., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: To investigate the distribution and clinical characteristics of pathogenic bacteria following hematopoietic stem cell transplantation (HSCT), as well as to provide a preliminary research foundation for key microbial monitoring, and clinical diagnosis and treatment of infections after HSCT in hematological patients. Methods: We retrospectively analyzed the clinical data of 190 patients who tested positive for microbial testing [G-bacteria blood culture and/or carbapenem-resistant organism (CRO) screening of perianal swabs] at our center from January 2018 to December 2022. Patients were divided into blood culture positive, perianal swab positive, and double positive groups based on the testing results. The three patient groups underwent statistical analysis and comparison. Results: The top four pathogenic bacteria isolated from sixty-three patients with G-bacteria bloodstream infection (BSI) were Escherichia coli (28 strains, 43.75% ), Klebsiella pneumonia (26 strains, 40.63% ), Pseudomonas aeruginosa (3 strains, 4.69% ), and Enterobacter cloacae (3 strains, 4.69% ). The top three pathogenic bacteria isolated from 147 patients with CRO perianal colonization were carbapenem-resistant Klebsiella pneumoniae (58 strains, 32.58% ), carbapenem-resistant Escherichia coli (49 strains, 27.53% ), and carbapenem-resistant Enterobacter cloacae (20 strains, 11.24% ). The 3-year disease-free survival (DFS ) and overall survival (OS) of double positive group patients were significantly lower compared to those in the blood culture and perianal swab positive groups (DFS: 35.6% vs 53.7% vs 68.6%, P =0.001; OS: 44.4% vs 62.4% vs 76.9%, P <0.001), while non-relapse mortality (NRM) was significantly higher (50.0% vs 34.9% vs 10.6%, P <0.001). Failed engraftment of platelets and BSI are independent risk factors for NRM ( P <0.001). Using polymyxin and/or ceftazidime-avibactam for more than 7 days is an independent protective factor for NRM ( P =0.035) . Conclusion: This study suggests that the occurrence of BSI significantly increases the NRM after HSCT in patients with hematological diseases; CRO colonization into the bloodstream has a significant impact on the DFS and OS of HSCT patients.

• Risk factors and prognosis of CRO infection in patients with hematological malignancies after CAR-T therapy are unclear. • CRO infection was an independent risk factor for poor outcome in patients treated with CAR-T therapy. • Hypoproteinemia and CRO colonization predicted the high-risk group of patients with CRO infection after CAR-T infusion. • MRSA-active drugs for prophylaxis of bacterial infection were associated with poor prognosis in patients treated with CAR-T therapy. • Compared with viral and fungal infections, CRO infection particularly affected 1-year prognosis of patients receiving CAR-T therapy. Carbapenem-resistant organisms (CRO) are a high priority issue because there are limited medications available to treat CRO infections, and these pathogens replicate rapidly in immunosuppressed patients, including those with hematological malignancy. Risk factors and prognosis of CRO infections after chimeric antigen receptor-modified T cells (CAR-T) therapy are unclear. This study was conducted to analyse the risk factors for CRO infection in patients with hematological malignancies following CAR-T therapy, and prognosis 1 year after CAR-T infusion. Patients who were diagnosed with hematological malignancies and treated with CAR-T therapy between June 2018 and December 2020 at our center were included. The case group consisted of 35 patients who developed CRO infections within 1 year of CAR-T infusion, and the control group comprised 280 patients who did not develop CRO infections. Shockingly, therapy failure occurred in 62.82% of CRO patients vs. 13.21% of the control group (P =0.000). Patients with CRO colonization (odds ratio [OR]=15.48, confidence interval [CI] (6.43-37.25), P =0.000) and hypoproteinemia (OR=2.84, CI (1.20-6.73), P =0.018) were susceptible to CRO infections. CRO infections (hazard ratio [HR]=4.40, CI (2.32-8.37), P =0.000), prophylaxis with combination regimens containing methicillin-resistant Staphylococcus aureus (MRSA)-active agents (HR=5.42, CI (2.65-11.11), P =0.000), and bacterial infections occurring within 30 days of CAR-T infusion (HR=1.97, CI (1.08-3.59), P =0.028) were risk factors for poor outcomes within 1 year. This study shows that prophylaxis of CRO infection should be a top priority in CAR-T therapy, the serum albumin level of patients should be dynamically monitored and interventions put in place if necessary, and caution is required in prophylaxis with anti-MRSA activity agents. [ABSTRACT FROM AUTHOR]

Objective: To explore the clinical characteristics of hospitalized patients with hematologic diseases complicated with carbapenem-resistant organisms (CRO) infection and analyze the risk factors of 30-day all-cause mortality., Methods: The clinical data and laboratory test data of 77 hospitalized patients with hematologic diseases complicated with CRO infection in department of hematology of the Third Hospital of Shanxi Medical University from January 2015 to December 2020 were retrospectively analysed, the risk factors of 30-day all-cause mortality after CRO infection were analyzed by multivariate logistic regression., Results: Among the total of 77 patients with hematologic diseases complicated with CRO infection, 29 died and 48 survived within 30 days of infection, with a case fatality rate of 37.66%. A total of 93 strains of CRO were isolated from these patients, of which Acinetobacter baumannii had the highest detection rate (25.81%, 24/93), followed by Pseudomonas aeruginosa (18.28%, 17/93). The lung was the most common site of CRO infection. The detected pathogens were highly resistant to carbapenems, and 64.52% (60/93) of the pathogens were resistant to imipenem with minimum inhibitory concentration (MIC)≥16 μg/ml. The results of the univariate analysis showed that albumin concentration <25 g/L ( P =0.048), serum creatinine concentration≥120 μmol/L ( P =0.023), age-adjusted Charlson comorbidity index (ACCI) ( P =0.037) and primary treatments (supportive treatment, immunosuppressive therapy, chemotherapy, HSCT) ( P =0.048) were significantly associated with 30-day all-cause mortality after infection. The results of multivariate logistic regression analysis showed that when CRO infection confirmed, albumin concentration <25 g/L ( P =0.014, OR =6.171), serum creatinine concentration≥120 μmol/L ( P =0.009, OR =10.867) were independent risk factors for 30-day mortality of patients with hematologic diseases complicated with CRO infection., Conclusion: The mortality rate of CRO-infected patients with hematologic diseases is high. The detected pathogenic bacteria are highly resistant to imipenem. The albumin concentration <25 g/L and the serum creatinine concentration≥ 120 μmol/L at diagnosis of CRO infection were independent risk factors for 30-day mortality of the patients with hematologic diseases.

Introduction: It is not clear whether polymyxin B/tigecycline (PMB/TGC) combination is better than PMB or TGC alone in the treatment of hospital-acquired pneumonia (HAP) caused by carbapenem-resistant organisms (CROs)., Methods: We conducted a multicenter, retrospective cohort study in patients with HAP caused by CROs. The primary outcome was 28-day mortality, and the secondary outcomes included clinical success and the incidence of acute kidney injury (AKI). Multivariate Cox regression analysis was performed to examine the relationship between antimicrobial treatments and 28-day mortality by adjusting other potential confounding factors., Results: A total of 364 eligible patients were included in the final analysis, i.e., 99 in the PMB group, 173 in the TGC group, and 92 in the PMB/TGC combination group. The 28-day mortality rate was 28.3% (28/99) in the PMB group, 39.3% (68/173) in the TGC group, and 48.9% (45/92) in the PMB/TGC combination group ( p = 0.014). The multivariate Cox regression model showed that there was a statistically significant lower risk of 28-day mortality among participants in the PMB group when compared with the PMB/TGC combination group [hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.31-0.81, p = 0.004] and that participants in the TGC group had a lower risk of 28-day mortality than in the PMB/TGC combination group but without statistical significance. The incidence of AKI in the PMB group (52.5%) and the PMB/TGC combination group (53.3%) was significantly higher than that in the TGC group (33.5%, p = 0.001)., Conclusion: The appropriate PMB/TGC combination was not superior to appropriate PMB therapy in the treatment of HAP caused by carbapenem-resistant Enterobacteriaceae /carbapenem-resistant Acinetobacter baumannii (CRE/CRAB) in terms of 28-day mortality., 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 © 2022 Chang, Wang, Zhao, Yang, Wu, Sun, Huang, Cheng, Chen, Song, Chen, Chen, Gan, Ma, Xing, Wang, Gu, Zou and Cao.)

Objective: To study the distribution and drug resistance of Carbapenem-Resistant Organism (CRO) and to analysis the risk factors of CRO 30-day mortality. Methods: A total of 181 patients with CRO infection diagnosed in Department of Hematology, Fujian Medical University Union Hospital from January 2018 to June 2020 were retrospectively investigated. The clinical and laboratory data of the patients were collected, the prognosis of patients diagnosed with CRO infection in day 30 was followed up, and the risk factors of prognosis were analyzed. The clinical significance of Carbapenem-Resistant Enterobacteriaceae (CRE) active screening was further evaluated in the CRE subgroup. Results: Among the total of 181 CRO isolates, 47.2% were CRE, 37.0% were Pseudomonas aeruginosa, and 32.6% were Klebsiella pneumoniae, which were highly resistant to carbapenem and had high MIC value, 76.8% (139/181) of CRO were MIC of imipenem resistance≥16 μg/ml. The main sources of isolates were blood and sputum. The 30-day all-cause mortality rates of patients with CRO or CRE infection were (41.4±3.7) % and (44.7±5.4) %, respectively. The COX multivariate regression analysis showed that the level of procalcitonin >0.2 ng/ml and the MIC value of imipenem resistance ≥ 16 μg/ml were independent risk factors for 30-day mortality of CRO infected patients. The CRE subgroup analysis showed that MIC value of imipenem resistance ≥16 μg/ml were independent risk factors for 30-day mortality of CRE infected patients. The 30-day cumulative survival rate of patients with CRE active screening was higher than the patients without CRE active screening [ (68.0±9.3) % vs (50.0±6.5) %, P =0.21]. Conclusion: The high MIC value of imipenem resistance isolates seriously affects the prognosis of patients with CRO infection in the hematology department, and the mortality rate was high. CRE active screening is expected for early prevention, early diagnosis, and early treatment for high-risk patients.

The optimal method to screen for gastrointestinal colonization with carbapenem-resistant organisms (CRO) has yet to be established. The direct MacConkey (direct MAC) plate method demonstrates high sensitivity for CRO detection, but established zone diameter (ZD) criteria for ertapenem (≤27 mm) and meropenem (≤32 mm) result in high rates of false positives upon confirmatory testing. To increase specificity, we screened for CRO in two high-risk wards using the direct MAC plate method, recorded ZDs for each sample, and generated receiver operating characteristic (ROC) curves to evaluate the optimal ZD cutoff criteria. Of 6,868 swabs obtained over an 18-month period, 4,766 (69%) had growth on MAC plates, and 2,500 (36%) met criteria for further evaluation based on previously established ZDs around the carbapenem disks. A total of 812 (12%) swabs were confirmed positive for at least one CRO and included 213 (3%) carbapenemase-producing organisms (CPO), resulting in a specificity of 78% for the direct MAC plate method. Reducing the ertapenem and meropenem ZDs to ≤25 mm improved specificity to 83%, decreasing the confirmatory testing workload by 32%. The sensitivities with the lower ZD criteria were 89% for CRO and 94% for CPO, respectively. The direct MAC plate method criteria for CRO testing can be modified to balance the sensitivity and specificity of CRO while reducing the burden on clinical microbiology laboratories. These modifications can be particularly helpful in regions with a low CRO prevalence., (Copyright © 2019 American Society for Microbiology.)