Approaches for Mitigating Microbial Biofilm-Related Drug Resistance: A Focus on Micro- and Nanotechnologies

Biofilms play an essential role in chronic and healthcare-associated infections and are more resistant to antimicrobials compared to their planktonic counterparts due to their (1) physiological state, (2) cell density, (3) quorum sensing abilities, (4) presence of extracellular matrix, (5) upregulation of drug efflux pumps, (6) point mutation and overexpression of resistance genes, and (7) presence of persister cells. The genes involved and their implications in antimicrobial resistance are well defined for bacterial biofilms but are understudied in fungal biofilms. Potential therapeutics for biofilm mitigation that have been reported include (1) antimicrobial photodynamic therapy, (2) antimicrobial lock therapy, (3) antimicrobial peptides, (4) electrical methods, and (5) antimicrobial coatings. These approaches exhibit promising characteristics for addressing the impending crisis of antimicrobial resistance (AMR). Recently, advances in the micro- and nanotechnology field have propelled the development of novel biomaterials and approaches to combat biofilms either independently, in combination or as antimicrobial delivery systems. In this review, we will summarize the general principles of clinically important microbial biofilm formation with a focus on fungal biofilms. We will delve into the details of some novel micro- and nanotechnology approaches that have been developed to combat biofilms and the possibility of utilizing them in a clinical setting.

Efficacy of Antimicrobial Lock Solutionsagainst Catheter-Related Infections in Hemodialysis Patients

INTRODUCTION: Hemodialysis patientsare at increased risk of catheter-related bloodstream infections (CRBSI) and catheter thrombosis asdialysis requires regular access to blood circulation through catheters. Antimicrobial Locking Solutions (ALS) containing anticoagulants and antimicrobial agents (antibiotic/non-antibiotic) are used to seal catheters in order to prevent thrombosis and CRBSI. PURPOSE: The investigation of internationalclinical studies regarding the efficacy and safety of the various ALS treatments for CRBSI in hemodialysis patients (HD patients) comparing to conventional approaches such as heparin treatment or catheter removal. METHODOLOGY: The review included prospective or retrospective clinical studies, randomized clinical trials or cohort studies published since 2015. Publications were retrieved from the “Pubmed”, “Google Scholar” and “Elsevier” databases using ‘catheter’, ‘catheter removal’, ‘hemodialysis’ ‘bacteremia’, ‘antimicrobial lock therapy’as key words. RESULTS: 17 articles were found to meet the criteria for this systematic review. These studies investigated locking solutions containing various antibiotic (Cefazolin, Gentamicin, Vancomycin, Cotrimoxazole, Daptomycin, Trimethoprim) or/and non-antibiotic agents (Citrate, taurolidine, ethanol, urokinase, Cathasept) +/- anticoagulants, single or in various combinations. The main objective of these studies was to identify the efficacy of ALS with respect to CRBSI risk rates, catheter exchange rates and related adverse effects. CONCLUSIONS: Antimicrobial Locking Therapy appears significantly beneficial forHD patients as it reduces CRBSI risk and prolongs catheter survival at considerable rates, so it should be seriously considered for systematic useagainst catheter-related infections. Further researchis required to establish safe and effective prevention and therapeutic protocols as alternatives to catheter removal practices.

Vancomycin-lock therapy for prevention of catheter-related bloodstream infection in very low body weight infants

Background: This study was to evaluate the effectiveness and safety of vancomycin- lock therapy for the prevention of catheter-related bloodstream infection (CRBSI) in very low body weight (VLBW) preterm infant patients. Methods: One hundred and thirty-seven cases of VLBW preterm infants who retained peripherally inserted central catheters (PICCs) were retrospectively reviewed, including 68 treating with heparin plus vancomycin (vancomycin-lock group) and 69 with heparin only (control group). The incidence of CRBSI, related pathogenic bacteria, adverse events during the treatment, complications, antibiotic exposure, PICC usage time, hospital stay, etc. were compared between the above two groups. Results: The incidence rate of CRBSI in the vancomycin-lock group (4.4%, 3/68) was significantly less than in the control group (21.7%, 15/69, p=0.004). Total antibiotic exposure time during the whole observation period was significantly shorter in the group than in the control group (11.2±10.0 vs 23.6±16.1 d; p<0.001). No hypoglycemia occurred during the locking, and the blood concentrations of vancomycin were not detectable. Conclusions: Vancomycin-lock may effectively prevent CRBSI in Chinese VLBW preterm infants and reduce the exposure time of antibiotics, without causing obvious side complications.

Vancomycin-lock therapy for prevention of catheter-related bloodstream infection in very low body weight infants

Background This study was to evaluate the effectiveness and safety of vancomycin- lock therapy for the prevention of catheter-related bloodstream infection (CRBSI) in very low body weight (VLBW) preterm infant patients. Methods One hundred and thirty-seven cases of VLBW preterm infants who retained peripherally inserted central catheters (PICCs) were retrospectively reviewed, including 68 treating with heparin plus vancomycin (vancomycin-lock group) and 69 with heparin only (control group). The incidence of CRBSI, related pathogenic bacteria, adverse events during the treatment, complications, antibiotic exposure, PICC usage time, hospital stay, etc. were compared between the above two groups. Results The incidence rate of CRBSI in the vancomycin-lock group (4.4%, 3/68) was significantly less than in the control group (21.7%, 15/69, p = 0.004). Total antibiotic exposure time during the whole observation period was significantly shorter in the group than in the control group (11.2 ± 10.0 vs 23.6 ± 16.1 d; p < 0.001). No hypoglycemia occurred during the locking, and the blood concentrations of vancomycin were not detectable. Conclusions Vancomycin-lock may effectively prevent CRBSI in Chinese VLBW preterm infants and reduce the exposure time of antibiotics, without causing obvious side complications.