UNASSIGNED: Some cohort studies have explored the effects and safety of polymyxin B (PMB) in comparison to other antibiotics for the treatment of nosocomial infections, yielding inconsistent results. This systematic review aims to explore the effectiveness and safety of PMB and compared it with other antibiotics.
UNASSIGNED: A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, and Web of Science, searching specific terms to identify quantitative cohort studies or RCTs that compared the effects of PMB with other antibiotics in terms of their efficacy and safety. The Newcastle-Ottawa Scale (NOS) was conducted to evaluate the risk of bias of observational studies. Odds ratios with 95% confidence intervals were used for outcome assessment. We evaluated heterogeneity using the I 2 test.
UNASSIGNED: A total of 22 observational trials were included in the analysis. The PMB group had a higher mortality rate compared to the control group (odds ratio: 1.84, 95% CI: 1.36-2.50, p<0.00001, I 2 = 73%). while, the ceftazidime-avibactam group demonstrated a distinct advantage with lower mortality rates, despite still exhibiting high heterogeneity (odds ratio 2.73, 95% confidence interval 1.59-4.69; p = 0.0003; I 2 = 53%). Additionally, the PMB group had a lower nephrotoxicity rate compared to the colistin group but exhibited high heterogeneity in the results (odds ratio 0.58, 95% CI 0.36-0.93; p = 0.02; I 2 = 73%).
UNASSIGNED: In patients with nosocomial infections, PMB is not superior to other antibiotics in terms of mortality, specifically when compared to ceftazidime-avibactam. However, PMB demonstrated an advantage in terms of nephrotoxicity compared to colistin.

Microbial biofilm formation creates a persistent and resistant environment in which microorganisms can survive, contributing to antibiotic resistance and chronic inflammatory diseases. Increasingly, biofilms are caused by multi-drug resistant microorganisms, which, coupled with a diminishing supply of effective antibiotics, is driving the search for new antibiotic therapies. In this respect, antimicrobial peptides (AMPs) are short, hydrophobic, and amphipathic peptides that show activity against multidrug-resistant bacteria and biofilm formation. They also possess broad-spectrum activity and diverse mechanisms of action. In this comprehensive review, 150 publications (from January 2020 to September 2023) were collected and categorized using the search terms \'polypeptide antibiotic agent\', \'antimicrobial peptide\', and \'biofilm\'. During this period, a wide range of natural and synthetic AMPs were studied, of which LL-37, polymyxin B, GH12, and Nisin were the most frequently cited. Furthermore, although many microbes were studied, Staphylococcus aureus and Pseudomonas aeruginosa were the most popular. Publications also considered AMP combinations and the potential role of AMP delivery systems in increasing the efficacy of AMPs, including nanoparticle delivery. Relatively few publications focused on AMP resistance. This comprehensive review informs and guides researchers about the latest developments in AMP research, presenting promising evidence of the role of AMPs as effective antimicrobial agents.

OBJECTIVE: Despite being clinically utilized for the treatment of infections, the limited therapeutic range of polymyxin B (PMB), along with considerable interpatient variability in its pharmacokinetics and frequent occurrence of acute kidney injury, has significantly hindered its widespread utilization. Recent research on the population pharmacokinetics of PMB has provided valuable insights. This study aims to review relevant literature to establish a theoretical foundation for individualized clinical management.
METHODS: Follow PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, Pop-PK studies of PMB were searched in PubMed and EMBASE database systems from the inception of the database until March 2023.
RESULTS: To date, a total of 22 population-based studies have been conducted, encompassing 756 subjects across six different countries. The recruited population in these studies consisted of critically infected individuals with multidrug-resistant bacteria, patients with varying renal functions, those with cystic fibrosis, kidney or lung transplant recipients, patients undergoing extracorporeal membrane oxygenation (ECMO) or continuous renal replacement therapy (CRRT), as well as individuals with obesity or pediatric populations. Among these studies, seven employed a one-compartmental model, with the range of typical clearance (CL) and volume (Vc) being 1.18-2.5L /h and 12.09-47.2 L, respectively. Fifteen studies employed a two-compartmental model, with the ranges of the clearance (CL) and volume of the central compartment (Vc), the volume of the peripheral compartment (Vp), and the intercompartment clearance (Q) were 1.27-8.65 L/h, 5.47-38.6 L, 4.52-174.69 L, and 1.34-24.3 L/h, respectively. Primary covariates identified in these studies included creatinine clearance and body weight, while other covariates considered were CRRT, albumin, age, and SOFA scores. Internal evaluation was conducted in 19 studies, with only one study being externally validated using an independent external dataset.
CONCLUSIONS: We conclude that small sample sizes, lack of multicentre collaboration, and patient homogeneity are the primary reasons for the discrepancies in the results of the current studies. In addition, most of the studies limited in the internal evaluation, which confined the implementation of model-informed precision dosing strategies.

UNASSIGNED: Clinically, Carbapenem-resistant Pseudomonas aeruginosa (CRPA) meningitis is extremely difficult to cure and has a high mortality rate. Intrathecal injection of polymyxins B is suggested to be an effective anti-infective means to treat intracranial infection with CRPA. However, due to the potential drug toxicity of polymyxin B in children, this regimen has rarely been reported in pediatrics.
UNASSIGNED: A 5-year-old male patient diagnosed with Epstein-Barr virus-induced hemophagocytic syndrome (HPS) exhibited persistent fever for over a month despite antibacterial and chemotherapy regimens. During hospitalization, the patient presented with unconsciousness, nystagmus, and myasthenia. Cerebrospinal fluid (CSF) analysis indicated elevated leukocyte counts and protein levels. Sputum and blood cultures, as well as metagenomic next-generation sequencing (mNGS) of CSF, identified CRPA. Intravenous and intrathecal polymyxin B administration resulted in temperature normalization and amelioration of consciousness disturbances and nystagmus. Subsequent CSF analysis yielded normal results, while polymyxin B treatment exhibited no nephrotoxicity or neurotoxicity.
UNASSIGNED: Intrathecal injection of polymyxin B in children with meningitis caused by CRPA is an effective treatment without remarkable adverse events.

The treatment of brucellosis suffers from a high recurrence rate and drug resistance. Our study researched the differences in efficacy and side effects between triple antibiotics therapy and dual antibiotics therapy in the treatment of brucellosis through a systematic review and meta-analysis.
We searched 4 English electronic databases and 2 Chinese electronic databases for randomized controlled trials and cohort studies published through September 2022 on the use of triple antibiotics versus dual antibiotics in the treatment of brucellosis. Overall outcome indicators were therapeutic failure rate, relapse rate, overall therapeutic failure rate, and side effect rate. Relative risk (RR) and 95% confidence intervals (95% CIs) were used as summary statistics. A fixed-effects model was used to combine the overall effect sizes.
The meta-analysis included 15 studies consisting of 11 randomized controlled trials and 4 cohort studies. Triple antibiotics showed better efficacy than dual antibiotics in a comparison of 3 overall outcome indicators (therapeutic failure rate (RR 0.42; 95% CI 0.30 to 0.59 heterogeneity P = 0.29, I2 = 15%), relapse rate (RR 0.29; 95% CI 0.18 to 0.45 heterogeneity P = 0.88, I2 = 0%), and overall therapeutic failure rate (RR 0.37; 95% CI 0.28 to 0.48 heterogeneity P = 0.35, I2 = 9%)). The incidence of side effects in patients with brucellosis treated with triple antibiotics was not significantly different from that in brucellosis patients treated with dual antibiotics (RR 0.85; 95% CI 0.67 to 1.06 heterogeneity P = 0.1, I2 = 35%). Sensitivity analyses showed robust results and Peter\'s test showed no publication bias. The results of subgroup analyses for the research type, drugs, and type of brucellosis were largely consistent with the overall outcome indicators, indicating the reliability and robustness of the overall results.
In the treatment of brucellosis, triple antibiotics have better efficacy than dual antibiotics and do not increase the incidence of side effects.

Spinal muscular atrophy (SMA) is a neurodegenerative disease that results in progressive and symmetric muscle weakness and atrophy of the proximal limbs and trunk due to degeneration of spinal alpha-motor neurons. Children are classified into types 1-3, from severe to mild, according to the time of onset and motor ability. Children with type 1 are the most severe, are unable to sit independently, and experience a series of respiratory problems, such as hypoventilation, reduced cough, and sputum congestion. Respiratory failure is easily complicated by respiratory infections and is a major cause of death in children with SMA. Most type 1 children die within 2 years of age. Type 1 children with SMA usually require hospitalization for lower respiratory tract infections and invasive ventilator-assisted ventilation in severe cases. These children are frequently infected with drug-resistant bacteria due to repeated hospitalizations and require long hospital stays requiring invasive ventilation. In this paper, we report a case of nebulization combined with intravenous polymyxin B in a child with spinal muscular atrophy with extensively drug-resistant Acinetobacter baumannii pneumonia, hoping to provide a reference for the treatment of children with extensively drug-resistant Acinetobacter baumannii pneumonia.

The aim of this integrative review was to identify whether the disinfection procedures performed prior to regenerative endodontic treatment were effective on biofilm removal from the root canals. The research was based on PubMed, Latin American and Caribbean Health Sciences Literature (Lilacs) and Scientific Electronic Library Online (SciELO) databases. Four articles were selected; one of the studies was in vivo and the others ex vivo. Different disinfection procedures were studied, characterised mainly by the use of intracanal medication, highlighting the double antibiotic paste, triple antibiotic paste and calcium hydroxide paste. Disinfection ability was evaluated against Enterococcus faecalis and multispecies biofilms by using the fluorescence technique and colony forming unit counting, for 7 to 21 days. Double antibiotic paste and triple antibiotic paste demonstrated excellent antibiofilm activity, unlike CH paste that showed limited disinfection, even when associated with different antimicrobial agents. Triple antibiotic paste was the most effective medication against biofilm.

UNASSIGNED: The objective of this review was to compare the effectiveness of Colistin monotherapy and combination therapy for the treatment of multidrug-resistant gram-negative bacterial infections.
UNASSIGNED: PubMed, Cochrane Library.
UNASSIGNED: In this systematic review, we included all retrospective and prospective studies and randomized controlled trials (RCTs) that compared intravenous polymyxin monotherapy and combination therapy with any other antibiotic for treating multidrug-resistant infections. Studies using inhaled polymyxins with 5 or less than 5 patients were excluded. The primary outcome was 30-day all-cause mortality and if not reported at day 30 we extracted and documented the closest time point. Both crude outcome rates and adjusted effect estimates were extracted for mortality.
UNASSIGNED: Search string used was \"(Colistin OR polymyxin) AND (Enterobacteriaceae OR Klebsiella OR Acinetobacter OR Escherichia coli OR Pseudomonas) AND (random OR prospective OR retrospective OR cohort OR observational OR blind).\" Thirty-nine studies were included in our analysis; out of which 6 RCTs were included and 9 studies used carbapenem as the adjunctive antibiotic. Each study was screened and reviewed for eligibility independently by two authors and data extrapolated on an Excel sheet.
UNASSIGNED: The meta-analysis of polymyxin monotherapy vs. combination therapy in multidrug-resistant infections yielded an odds ratio (OR) of 0.81 (95% confidence interval [CI]: 0.65-1.01) with minimal heterogeneity (I 2 = 40%), whereas pooled analysis of this comparison in studies that included carbapenem as combination therapy yielded an OR of 0.64 (CI: 0.40-1.03; I 2 = 62%). Likewise, the pooled analysis of the RCTs yielded an OR of 0.82 (95% CI: 0.58-1.16, I 2 = 22%). All these showed no statistical significance. However, it was seen that polymyxin combination therapy was more effective in multidrug-resistant infections compared to polymyxin monotherapy. The effectiveness was more glaring when carbapenems were used as the combination drug instead of any other antibiotic and more so in many in vitro studies that used polymyxin combination therapy.
UNASSIGNED: Although statistically insignificant, it would be prudent to use polymyxin combination therapy to treat multidrug-resistant gram-negative bacilli (GNB) infection over monotherapy with preference to use carbapenem as the adjunct alongside polymyxins.
UNASSIGNED: Samal S, Mishra SB, Patra SK, Rath A, Dash A, Nayak B, et al. Polymyxin Monotherapy vs. Combination Therapy for the Treatment of Multidrug-resistant Infections: A Systematic Review and Meta-analysis. Indian J Crit Care Med 2021;25(2):199-206.

Polymyxins are last-resort antibiotics re-emerged to treat infections caused by multidrug resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacterial infections. However, polymyxin-associated nephrotoxicity has become the main safety concern. Therefore, we conducted this systematic review and meta-analysis on polymyxin-induced nephrotoxicity and its predictors using studies conducted based on the validated RIFLE (Risk, Injury, Failure, Loss of Function and End-stage renal disease) criteria of acute kidney damage. Literature search was carried out through visiting legitimate databases and indexing services including PubMed, MEDLINE (Ovid®), EMBASE (Ovid®), and Scopus to retrieve relevant studies. Following screening and eligibility evaluation, relevant data were extracted from included studies and analyzed using STATA 15.0 and Rev-Man 5.3. Inverse variance method with random effects pooling model was used for the analysis of outcome measures at 95% confidence interval. Besides, meta-regression, meta-influence, and publication bias analyses were conducted. A total of 48 studies involving 6,199 adult patients aged ≥ 18 years were included for systematic review and meta-analysis. The pooled incidence of polymyxin-induced nephrotoxicity was found to be 45% (95% CI: 41- 49%; I2 = 92.52%). Stratifying with RIFLE severity scales, pooled estimates of polymyxin-treated patients identified as \'risk\', \'injury\' and \'failure\' were 17% (95% CI: 14-20%), 13% (95% CI: 11-15%), and 10% (95% CI: 9-11%), respectively. Besides, the pooled incidence of colistin-induced nephrotoxicity was about 48% (95% CI: 42-54%), whereas that of polymyxin B was 38% (95% CI: 32-44%). Likewise, colistin had 37% increased risk of developing nephrotoxicity compared to the polymyxin B treated cohorts (RR = 1.37, 95% CI: 1.13-1.67; I2 = 57%). Older age (AOR = 1.03, 95% CI: 1.01-1.05), daily dose (AOR = 1.46, 95% CI: 1.09-1.96), underlying diabetes mellitus (AOR = 1.81, 95% CI: 1.25-2.63), and concomitant nephrotoxic drugs (AOR = 2.31, 95% CI: 1.79-3.00) were independent risk factors for polymyxin-induced nephrotoxicity. Patients with high serum albumin level were less likely (AOR = 0.69, 95% CI: 0.56-0.85] to experience nephrotoxicity compared to those with low albumin level. Despite the resurgence of these antibiotics for the chemotherapy of MDR/XDR-Gram-negative superbugs, the high incidence of nephrotoxicity has become a contemporary clinical concern. Being elderly, high daily dose, having underlying diseases such as diabetes, and use of concomitant nephrotoxic drugs were independent predictors of nephrotoxicity. Therefore, therapeutic drug monitoring should be done to these patients to outweigh the potential benefits of polymyxin therapy from its risk.

To evaluate the efficacy and safety of Polymyxin B-immobilized hemoperfusion (PMX-HP) against sepsis or septic shock.
We searched databases (PubMed, EMBASE and Cochrane Library) to identify eligible randomized controlled trials (RCTs). The primary outcomes we included in this review were mortality at the longest follow-up available and serious adverse events associated with treatments. We used the Cochrane risk of bias assessment tool to evaluate risk of bias. Trial Sequential Analysis (TSA) was performed to assess the conclusion reached in our research.
Thirteen studies including 1163 patients were identified. Use of PMX-HP could reduce overall mortality [relative risk (RR) 0.68, 95% confidence interval (CI) 0.51-0.91, P = 0.01]. An interesting finding was that the mortality of patients in Acute Physiology and Chronic Health Evaluation (APACHE II) scores <25 group (RR 0.64, 95% CI 0.52-0.78, P < 0.0001) and sepsis group (RR 0.48, 95% CI 0.32-0.72, P = 0.0003) significantly decreased after PMX-HP treatment. The result also showed that PMX-HP could reduce endotoxin levels [Standardized mean difference (SMD) -1.53, 95% CI -2.92- -0.13, P = 0.03] and improve mean arterial pressure (SMD 1.07, 95% CI 0.14-2.01, P = 0.02). Serious adverse events between the PMX-HP group and standard therapy group were not significantly different (RR 2.16, 95% CI 0.97-4.80, I2 = 0%, P = 0.06). However, TSA did not provide conclusive evidence and more high quality RCTs were required.
Using PMX-HP to treat patients with less severe sepsis can reduce overall mortality and is safe. Treatment efficacy may benefit from the reduction of endotoxin level and the improvement of hemodynamics. More high quality RCTs are required to further evaluate the clinical role of PMX-HP against severe sepsis or septic shock.