Vancomycin-resistant Staphylococcus aureus (VRSA), Vancomycin-intermediate S. aureus (VISA) and heterogeneous VISA (hVISA) are subject to vancomycin treatment failure. The aim of the present study was to determine their precise prevalence and investigate prevalence variability depending on different years and locations. Several international databases including Medline (PubMed), Embase and Web of Sciences were searched (data from 1997 to 2019) to identify studies that addressed the prevalence of VRSA, VISA and hVISA among human clinical isolates around the world. Subgroup analyses and meta-regression were conducted to indicate potential source of variation. Publication bias was assessed using Egger’s test. Statistical analyses were conducted using STATA software (version 14.0). Data analysis showed that VRSA, VISA and hVISA isolates were reported in 23, 50 and 82 studies, with an overall prevalence of 1.5% among 5855 S. aureus isolates, 1.7% among 22,277 strains and 4.6% among 47,721 strains, respectively. The overall prevalence of VRSA, VISA, and hVISA before 2010 was 1.2%, 1.2%, and 4%, respectively, while their prevalence after this year has reached 2.4%, 4.3%, and 5.3%. The results of this study showed that the frequency of VRSA, VISA and hVISA after 2010 represent a 2.0, 3.6 and 1.3-fold increase over prior years. In a subgroup analysis of different strain origins, the highest frequency of VRSA (3.6%) and hVISA (5.2%) was encountered in the USA while VISA (2.1%) was more prevalent in Asia. Meta-regression analysis showed significant increasing of VISA prevalence in recent years ( p value ≤ 0.05). Based on the results of case reports (which were not included in the calculations mentioned above), the numbers of VRSA, VISA and hVISA isolates were 12, 24 and 14, respectively, among different continents. Since the prevalence of VRSA, VISA and hVISA has been increasing in recent years (especially in the Asian and American continents), rigorous monitoring of vancomycin treatment, it’s the therapeutic response and the definition of appropriate control guidelines depending on geographical regions is highly recommended and essential to prevent the further spread of vancomycin-resistant S. aureus .

Nowadays the most important problem in the treatment of bacterial infections is the appearance of MDR (multidrug-resistant), XDR (extensively drug-resistant) and PDR (pan drug-resistant) bacteria and the scarce prospects of producing new antibiotics. There is renewed interest in revisiting the use of bacteriophage to treat bacterial infections. The practice of phage therapy, the application of phages to treat bacterial infections, has been around for approximately a century. Phage therapy relies on using lytic bacteriophages and purified phage lytic proteins for treatment and lysis of bacteria at the site of infection. Current research indicates that phage therapy has the potential to be used as an alternative to antibiotic treatments. It is noteworthy that, whether phages are used on their own or combined with antibiotics, phages are still a promising agent to replace antibiotics. So, this review focuses on an understanding of challenges of MDR, XDR, and PDR bacteria and phages mechanism for treating bacterial infections and the most recent studies on potential phages, cocktails of phages, and enzymes of lytic phages in fighting these resistant bacteria.

Biofilms are communities of microorganisms that are formed on and attached to living or nonliving surfaces and are surrounded by an extracellular polymeric material. Biofilm formation enjoys several advantages over the pathogens in the colonization process of medical devices and patients' organs. Unlike planktonic cells, biofilms have high intrinsic resistance to antibiotics and sanitizers, and overcoming them is a significant problematic challenge in the medical and food industries. There are no approved treatments to specifically target biofilms. Thus, it is required to study and present innovative and effective methods to combat a bacterial biofilm. In this review, several strategies have been discussed for combating bacterial biofilms to improve healthcare, food safety, and industrial process.

Multi-Drug Resistant (MDR) Pseudomonas aeruginosa is one of the most important bacterial pathogens that causes infection with a high mortality rate due to resistance to different antibiotics. This bacterium prompts extensive tissue damage with varying factors of virulence, and its biofilm production causes chronic and antibiotic-resistant infections. Therefore, due to the non-applicability of antibiotics for the destruction of P. aeruginosa biofilm, alternative approaches have been considered by researchers, and phage therapy is one of these new therapeutic solutions. Bacteriophages can be used to eradicate P. aeruginosa biofilm by destroying the extracellular matrix, increasing the permeability of antibiotics into the inner layer of biofilm, and inhibiting its formation by stopping the quorum-sensing activity. Furthermore, the combined use of bacteriophages and other compounds with anti-biofilm properties such as nanoparticles, enzymes, and natural products can be of more interest because they invade the biofilm by various mechanisms and can be more effective than the one used alone. On the other hand, the use of bacteriophages for biofilm destruction has some limitations such as limited host range, high-density biofilm, sub-populate phage resistance in biofilm, and inhibition of phage infection via quorum sensing in biofilm. Therefore, in this review, we specifically discuss the use of phage therapy for inhibition of P. aeruginosa biofilm in clinical and in vitro studies to identify different aspects of this treatment for broader use.

Objective: Methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative

Background P. aeruginosa is considered as one of the most important pathogens, and high antibiotic resistance to P. aeruginosa has become an alarming concern. This study attempts to further improve curcumin solubility and stability by producing the involved nanoparticle and investigate the effect of this nanoparticle on those virulence genes of P. aeruginosa in pathogenicity and biofilm formation. Methods In this study, the curcumin nanoparticles were synthesized and characterized, and the antibacterial and antibiofilm effects of Nano-curcumin and curcumin were investigated by microdilution broth and microtiter plate, respectively. In addition, cytotoxic effect of Nano-curcumin on human epithelial cell lines (A549) was determined. The effects of Nano-curcumin on P. aeruginosa virulence genes, mexD, mexB, and mexT (efflux pumps), lecA (adhesion), nfxB (negative regulator of MexCD-OprJ), and rsmZ (biofilm formation) were determined using real-time quantitative PCR. Results Synthesized Nano-curcumins were soluble in water, which inhibited the growth of multidrug-resistant (MDR) P. aeruginosa at 128 µg/mL, whereas it was inhibited at 256 µg/mL for soluble curcumin in DMSO. Sub-inhibitory concentrations of Nano-curcumin reduced biofilm formation and, at 64 μg/mL, disrupted 58% of the established bacterial biofilms. In addition, curcumin nanoparticle downregulated the transcription of virulence genes except nfxB and exerted no cytotoxic effect on human epithelial cell lines (A549). Conclusions Results suggest that Nano-curcumin could be potentially used to reduce P. aeruginosa virulence and biofilm. However, in vivo studies with respect to an animal model are necessary to validate these results.

In this study, we report the insertion sequence ISPpu21 in the oprD porin gene of carbapenem-resistant Pseudomonas aeruginosa isolates from burn patients in Tehran, Iran. Antibiotic susceptibility tests for P. aeruginosa isolates were determined. Production of metallo-β-lactamases (MBLs) and carbapenemase was evaluated and the β-lactamase-encoding and aminoglycoside-modifying enzyme genes were investigated by PCR and sequencing methods. The mRNA transcription level of oprD and mex efflux pump genes were evaluated by real-time PCR. The outer membrane protein profile was determined by SDS–PAGE. The genetic relationship between the P. aeruginosa isolates was assessed by random amplified polymorphic DNA PCR. In all, 10.52% (10/95) of clinical isolates of P. aeruginosa harboured the ISPpu21 insertion element in the oprD gene. The extended-spectrum β-lactamase-encoding gene in ISPpu21-carrying isolates was blaTEM. PCR assays targeting MBL and carbapenemase-encoding genes were also negative in all ten isolates. The rmtA, aadA, aadB and armA genes were positive in all ISPpu21 harbouring isolates. The relative expression levels of the mexX, mexB, mexT and mexD genes in ten isolates ranged from 0.1- to 1.4-fold, 1.1- to 3.68-fold, 0.3- to 8.22-fold and 1.7- to 35.17-fold, respectively. The relative expression levels of the oprD in ten isolates ranged from 0.57- to 35.01-fold, which was much higher than those in the control strain P. aeruginosa PAO1. Evaluation of the outer membrane protein by SDS–PAGE suggested that oprD was produced at very low levels by all isolates. Using random amplified polymorphic DNA PCR genotyping, eight of the ten isolates containing ISPpu21 were shown to be clonally related. The present study describes a novel molecular mechanism, ISPpu21 insertion of the oprD gene, associated with carbapenem resistance in clinical P. aeruginosa isolates.

Wound infection kills a large number of patients worldwide each year. Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa are the most important colonizing pathogens of wounds that, with various virulence factors and impaired immune system, causes extensive tissue damage and nonhealing wounds. Furthermore, the septicemia caused by these pathogens increases the mortality rate due to wound infections. Because of the prevalence of antibiotic resistance in recent years, the use of antibiotics to inhibit these pathogens has been restricted, and the topical application of antibiotics in wound infections increases antibiotic resistance. Therefore, finding a new therapeutic strategy against wound infections is so essential since these infections have a destructive effect on the patient's mental health and high medical costs. In this review, we discussed the use of phages for the prevention of multidrug-resistant (MDR) bacteria, causing wound infection and their role in wound healing in animal models and clinical trials. The results showed that phages have a high ability to inhibit different wound infections caused by MDR bacteria, heal the wound faster, have lower side effects and toxicity, destroy bacterial biofilm, and they are useful in controlling immune responses. Many studies have used animal models to evaluate the function of phages, and this study appears to have a positive impact on the use of phages in clinical practice and the development of a new therapeutic approach to control wound infections, although there are still many limitations.