Background 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.

Polymyxin B-Based Regimens for Patients Infected with Carbapenem-Resistant Gram-Negative Bacteria: Clinical and Microbiological Efficacy, Mortality, and Safety

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.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.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.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. 

https://www.dovepress.com/getfile.php?fileID=79286

In recent years, polymyxin B‐associated acute kidney injury (PB‐AKI) in critically ill patients has been reported frequently, but polymyxin B (PB) is mainly cleared through non‐renal pathways, and the reasons of PB‐AKI remain unclear. The aim of this study was to investigate the relationship between the serum concentration of PB and PB‐AKI. We conducted a prospective cohort study in an intensive care unit between May 2019 and July 2021. Over the study period, 52 patients were included and divided into an AKI group (n = 26) and a non‐AKI group (n = 26). The loading dose of PB in the AKI group was significantly higher than that in the non‐AKI group. The C1/2, Cmin, and estimated area under the concentration–time curve (AUC)0–24 of PB in the AKI group were dramatically increased compared with those in the non‐AKI group, but the Cmax between the two groups showed no differences. Upon obtaining the ROC curve, the areas for the C1/2, Cmin, and estimated AUC0–24 were 0.742, 0.710, and 0.710, respectively. The sensitivity was ascertained to be 61.54%, and the specificity was 76.92% when the cutoff value for the estimated AUC0–24 of 97.72 mg·h/L was used preferentially. The incidence of PB‐AKI is high and related to the loading dose of PB. PB‐AKI could be predicted when the estimated AUC0–24 of PB was greater than 97.72 mg·h/L.

Correlation between the drug concentration of polymyxin B and polymyxin B‐associated acute kidney injury in critically ill patients: A prospective study

Background Carbapenem-resistant gram-negative bacteria (CR-GNB) are becoming increasingly important bacterial pathogens in critically ill patients. Several clinicians use Intravenous colistin sulfate to treat infections due to CR-GNB, although the clinical data is limited. The aim of our retrospective observational study was to evaluate the effectiveness and nephrotoxicity of intravenous colistin sulfate in the treatment of CR-GNB infections. Methods Fifty critically ill intensive care patients with infections due to CR-GNB were retrospectively enrolled between January 2020 and December 2021 in the Zhejiang Provincial People’s Hospital. Favorable clinical response rate, bacterial clearance rate, nephrotoxicity, and 28-day mortality were evaluated. Results The overall favorable clinical response rate was 58%, the bacterial clearance rate was 40%, and the 28-day all-cause mortality was 44%. Temperature, neutrophil count, C-reaction protein (CRP), procalcitonin (PCT), creatinine (Cr), and lactate levels were also significantly decreased (P<0.05). The major adverse reaction is nephrotoxicity, and renal function was evaluated on the day before and after treatment with colistin sulfate. Possible nephrotoxicity was observed in three patients (6%). Backward logistic regression was conducted to determine risk factors for the nephrotoxicity of colistin sulfate, the result showed there were no significant differences in the duration and dose of colistin sulfate. Conclusions Our results provide evidence for the positive clinical efficacy and safety of colistin sulfate. Appropriate use of colistin sulfate may be viable and safe in the treatment of severe infections caused by CR-GNB.

/pdf/clinical-efficacy-and-nephrotoxicity-of-intravenous-colistin-3m554rlr.pdf

Clinical efficacy and nephrotoxicity of intravenous colistin sulfate in the treatment of carbapenem-resistant gram-negative bacterial infections: a retrospective cohort study

BACKGROUND Polymyxin-induced nephrotoxicity is a major safety concern in clinical practice due to long-term adverse outcomes and high mortality. AIM To conducted a systematic review and meta-analysis of the prevalence and potential predictors of polymyxin-induced nephrotoxicity in adult intensive care unit (ICU) patients. METHODS PubMed, EMBASE, the Cochrane Library and Reference Citation Analysis database were searched for relevant studies from inception through May 30, 2022. The pooled prevalence of polymyxin-induced nephrotoxicity and pooled risk ratios of associated factors were analysed using a random-effects or fixed-effects model by Stata SE ver. 12.1. Additionally, subgroup analyses and meta-regression were conducted to assess heterogeneity. RESULTS A total of 89 studies involving 12234 critically ill adult patients were included in the meta-analysis. The overall pooled incidence of polymyxin-induced nephrotoxicity was 34.8%. The pooled prevalence of colistin-induced nephrotoxicity was not higher than that of polymyxin B (PMB)-induced nephrotoxicity. The subgroup analyses showed that nephrotoxicity was significantly associated with dosing interval, nephrotoxicity criteria, age, publication year, study quality and sample size, which were confirmed in the univariable meta-regression analysis. Nephrotoxicity was significantly increased when the total daily dose was divided into 2 doses but not 3 or 4 doses. Furthermore, older age, the presence of sepsis or septic shock, hypoalbuminemia, and concomitant vancomycin or vasopressor use were independent risk factors for polymyxin-induced nephrotoxicity, while an elevated baseline glomerular filtration rate was a protective factor against colistin-induced nephrotoxicity. CONCLUSION Our findings indicated that the incidence of polymyxin-induced nephrotoxicity among ICU patients was high. It emphasizes the importance of additional efforts to manage ICU patients receiving polymyxins to decrease the risk of adverse outcomes.

https://doi.org/10.12998/wjcc.v10.i31.11466

Prevalence of polymyxin-induced nephrotoxicity and its predictors in critically ill adult patients: A meta-analysis

Risk factors for polymyxin B-associated acute kidney injury.

AIM
To investigate the effectiveness of different dressings on pressure injuries and screen the dressings for efficacy.


DESIGN
Systematic review and network meta-analysis.


METHODS
Articles published from several electronic databases and other resources were selected. Two reviewers independently selected studies, extracted data and assessed the quality of selected studies.


RESULTS
Twenty-five studies that contained data on moist dressings (hydrocolloidal dressing, foam dressing, silver ion dressing, biological wound dressing, hydrogel dressing, polymeric membrane dressing) and sterile gauze dressings (traditional gauze dressings) were included. All RCTs were at a medium to high risk of bias. Moist dressings were found to be more advantageous than the traditional dressings. Hydrocolloid dressings [RR = 1.38, 95% CI (1.18, 1.60)] showed a higher cure rate than sterile gauze dressing and foam dressings [RR = 1.37, 95% CI (1.16, 1.61)]. Silver ion dressings [RR = l.37, 95% CI (1.08, 1. 73)] showed a higher cure rate than sterile gauze dressings. Sterile gauze dressing dressings [RR = 0.51, 95% CI (0.44, 0.78)] showed a lower cure rate compared with polymeric membrane dressings; whereas Sterile gauze dressing dressings [RR = 0.80, 95% CI (0.47, 1.37)] had a lower cure rate compared to biological wound dressings. Foam and hydrocolloid dressings were associated with the least healing time. Few dressing changes were required for moist dressings.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/nop2.1867

Efficacy of different types of dressings on pressure injuries: Systematic review and network meta-analysis.

Artesunate delays the dysfunction of age-related intestinal epithelial barrier by mitigating endoplasmic reticulum stress/unfolded protein response

SHR-1222, a novel humanized monoclonal antibody targeting sclerostin, has been shown to induce bone formation and decrease bone resorption at a single dose ranging 50–400 mg in our previous phase 1 trial. This study was a randomized, double-blind, placebo-controlled, dose-escalation phase 1 trial, which further investigated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of multiple ascending doses of SHR-1222 in women with postmenopausal osteoporosis (POP). A total of 105 women with POP were enrolled and randomly assigned. Twenty-one received placebo and eighty-four received SHR-1222 sequentially (100 mg QM, n=4; 200 or 300 mg QM, n=20; and 400 or 600 mg Q2M, n=20). The most common adverse events included increased blood parathyroid hormone, increased low-density lipoprotein, increased blood alkaline phosphatase, increased blood cholesterol, back pain, and arthralgia, the majority of which were mild in severity without noticeable safety concerns. Serum SHR-1222 exposure (Cmax,ss and AUC0-tau,ss) increased in a greater than dose-proportional manner. Following multiple doses of SHR-1222, the bone formation markers (terminal propeptide of type I procollagen, bone-specific alkaline phosphatase, and osteocalcin) increased in a dose-dependent manner, whereas the bone resorption marker (β-C-telopeptide) was downregulated. Accordingly, BMD gains in the lumbar spine, total hip, and femoral neck were observed. The maximum BMD increase from baseline at the lumbar spine was detected in the 300 mg QM cohort (14.6% vs. 0.6% in the placebo group on day 169). Six (6/83; 7.2%) subjects developed anti-SHR-1222 antibodies with no discernible effects on PKs, PDs, and safety. Thus, multiple doses of SHR-1222 showed an acceptable safety profile and dose-dependent plasma exposure in women with POP, and could improve their BMD rapidly and prominently by promoting bone formation and inhibiting bone resorption. These findings further support SHR-1222 as a potential alternative agent for the treatment of POP.

/pdf/multiple-doses-of-shr-1222-a-sclerostin-monoclonal-antibody-1hto0qzt.pdf

Multiple doses of SHR-1222, a sclerostin monoclonal antibody, in postmenopausal women with osteoporosis: A randomized, double-blind, placebo-controlled, dose-escalation phase 1 trial

Hong Chen

Papers

Risk factors for polymyxin B-associated acute kidney injury.

Efficacy of different types of dressings on pressure injuries: Systematic review and network meta-analysis.

Artesunate delays the dysfunction of age-related intestinal epithelial barrier by mitigating endoplasmic reticulum stress/unfolded protein response

Multiple doses of SHR-1222, a sclerostin monoclonal antibody, in postmenopausal women with osteoporosis: A randomized, double-blind, placebo-controlled, dose-escalation phase 1 trial