Antimicrobial resistance among clinical Vibrio cholerae non-O1/non-O139 isolates: systematic review and meta-analysis.

Non-O1/non-O139 Vibrio cholerae (NOVC) are nonpathogenic or asymptomatic colonizers in humans, but they may be related to intestinal or extra-intestinal (severe wound infections or sepsis) infections in immunocompromised patients.The present study aimed to evaluate the weighted pooled resistance (WPR) rates in clinical NOVC isolates based on different years, areas, quality, antimicrobial susceptibility testing (AST), and resistance rates. We systematically searched the articles in PubMed, Scopus, and Embase (until January 2020). Data analyses were performed using the Stata software program (version 17). A total of 16 studies that had investigated 824 clinical NOVC isolates were included in the meta-analysis. The majority of the studies were conducted in Asia (n = 14) and followed by Africa (n = 2). The WPR rates were as follows: erythromycin 10%, ciprofloxacin 5%, cotrimoxazole 27%, and tetracycline 13%. There was an increase in resistance to ciprofloxacin, nalidixic acid, and gentamicin, norfloxacin during the period from 2000 to 2020. On the contrary, there was a decreased resistance to erythromycin, tetracycline, chloramphenicol, cotrimoxazole, ampicillin, streptomycin, kanamycin, and neomycin during the period from 2000 to 2020. The lowest resistance rate were related to gentamicin, kanamycin, ciprofloxacin, and chloramphenicol against NOVC strains. However, temporal changes in antimicrobial resistance rate were found in our study. We established continuous surveillance, careful appropriate AST, and limitations on improper antibiotic usage, which are essential, especially in low-income countries.

Development of innovative multi-epitope mRNA vaccine against Pseudomonas aeruginosa using in silico approaches.

The rising issue of antibiotic resistance has made treating Pseudomonas aeruginosa infections increasingly challenging. Therefore, vaccines have emerged as a viable alternative to antibiotics for preventing P. aeruginosa infections in susceptible individuals. With its superior accuracy, high efficiency in stimulating cellular and humoral immune responses, and low cost, mRNA vaccine technology is quickly replacing traditional methods. This study aimed to design a novel mRNA vaccine by using in silico approaches against P. aeruginosa. The research team identified five surface and antigenic proteins and selected their appropriate epitopes with immunoinformatic tools. These epitopes were then examined for toxicity, allergenicity and homology. The researchers also checked their presentation and identification by major histocompatibility complex cells and other immune cells through valuable tools like molecular docking. They subsequently modeled a multi-epitope protein and optimized it. The mRNA was analyzed in terms of structure and stability, after which the immune system's response against the new vaccine was simulated. The results indicated that the designed mRNA construct could be an effective and promising vaccine that requires laboratory and clinical trials.

Molecular typing and antibiotic resistance patterns among clinical isolates of Acinetobacter baumannii recovered from burn patients in Tehran, Iran.

Acinetobacter baumannii (A. baumannii) is now considered a highly resistant pathogen to various types of antibiotics. Therefore, tracking the source of its prevalence and continuous control is crucial. This study aimed to determine antibiotic resistance and perform various molecular typing methods on clinical isolates of A. baumannii isolated from hospitalized burn patients in Shahid Motahari Burn Hospital, Tehran, Iran. Hospital isolates were confirmed by phenotypic and molecular methods. Then the sensitivity to different antibiotics was determined using the minimum inhibitory concentration (MIC) method. In order to perform molecular typing, three-locus dual assay multiplex polymerase chain reaction (PCR), multiple-locus variable-number tandem repeat analysis (MLVA), and multilocus sequence typing (MLST) methods were used. Among the 60 isolates collected, the frequencies of multidrug-resistant (MDR) and extensively drug-resistant (XDR) isolates were 90 and 10%, respectively. The most effective antibiotics were colistin with 100% and tigecycline with 83.33% sensitivity. Isolates were 100% resistant to piperacillin/tazobactam and cephalosporins, and 68.3% were resistant to carbapenem. The results of multiplex PCR showed five groups that international clone I (IC I) and IC II were the most common. The MLVA method identified 34 MLVA types (MTs), 5 clusters, and 25 singletons. Multilocus sequence typing results for tigecycline-resistant isolates showed seven different sequence types (STs). Increasing antibiotic resistance in A. baumannii isolates requires careful management to control and prevent the occurrence of the pre-antibiotic era. The results of this study confirm that the population structure of A. baumannii isolates has a high diversity. More extensive studies are needed in Iran to better understand the epidemiology of A. baumannii.

Antibacterial activity of recently approved antibiotics against methicillin-resistant Staphylococcus aureus (MRSA) strains: A systematic review and meta-analysis.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infections are considered an important public health problem, and treatment options are limited. Accordingly, in this meta-analysis, we analyzed published studies to survey in vitro activity of recently approved antibiotics against MRSA isolates. METHODS: We searched electronic databases; PubMed, Scopus, and Web of Science to identify relevant studies (until November 30, 2020) that have focused on the in vitro activity of telavancin, dalbavancin, oritavancin, and tedizolid against MRSA isolates. Statistical analyses were conducted using STATA software (version 14.0). RESULTS: Thirty-eight studies were included in this meta-analysis. Overall in vitro activity of tedizolid on 12,204 MRSA isolates was 0.250 and 0.5 µg/mL for MIC50 and MIC90, (minimum inhibitory concentration at which 50% and 90% of isolates were inhibited, respectively), respectively. The overall antibacterial activity of dalbavancin on 28539 MRSA isolates was 0.060 and 0.120 µg/mL for MIC50 and MIC90, respectively. The overall antibacterial activity of oritavancin on 420 MRSA isolates was 0.045 and 0.120 µg/mL for MIC50 and MIC90, respectively. The overall antibacterial activity of telavancin on 7353 MRSA isolates was 0.032 and 0.060 µg/mL for MIC50 and MIC90, respectively. The pooled prevalence of tedizolid, telavancin, and dalbavancin susceptibility was 100% (95% CI: 100-100). CONCLUSION: Telavancin, dalbavancin, oritavancin, and tedizolid had potent in vitro activity against MRSA isolates. The low MICs and high susceptibility rates of these antibiotics recommend a hopeful direction to introduce useful antibiotics in treating MRSA infections in the future.

Antimicrobial resistance in Vibrio cholerae O1/O139 clinical isolates: a systematic review and meta-analysis.

OBJECTIVES: Vibrio cholerae O1/O139 is responsible for cholera epidemics that remains a huge public health menace across the globe. Furthermore, an increasing resistance rate among V. cholerae strains has been reported around the world. Therefore, the objective of this meta-analysis was to evaluate the weighted pooled resistance (WPR) rates in clinical V. cholerae O1/O139 isolates based on different years, areas, antimicrobial susceptibility testing, and resistance rates. RESEARCH DESIGN AND METHODS: We searched the studies in PubMed, Scopus, Embase, and Web of Science (until January 2020). Statistical analyses were conducted using STATA software (ver. 14.0). RESULTS: A total of 139 studies investigating 24,062 V. cholerae O1/O139 isolates were analyzed. The majority of the studies originated in Asia (n = 102). The WPR rates were as follows: azithromycin 1%, erythromycin 36%, ciprofloxacin 3%, cotrimoxazole 79%, doxycycline 7%, and tetracycline 20%. There was increased resistance to cotrimoxazole, ciprofloxacin, and tetracycline during the 1980-2020 years. CONCLUSIONS: Temporal changes in antibiotic resistance rate found in this study demonstrated the critical continuous surveillance of antibiotic resistance. Also, ciprofloxacin, azithromycin, gentamicin, cephalexin, imipenem, ofloxacin, and norfloxacin were found to be the best antibiotics against V. cholera, with the highest and the lowest effectiveness resistance rate.

Global status of antimicrobial resistance among environmental isolates of Vibrio cholerae O1/O139: a systematic review and meta-analysis.

BACKGROUND: Vibrio cholerae O1/O139 were the predominant circulating serogroups exhibiting multi-drug resistance (MDR) during the cholera outbreak which led to cholera treatment failures. OBJECTIVE: This meta-analysis aimed to evaluate the weighted pooled resistance (WPR) rates in V. cholerae O1/O139 isolates obtained from environmental samples. METHODS: We systematically searched the articles in PubMed, Scopus, and Embase (until January 2020). Subgroup analyses were then employed by publication year, geographic areas, and the quality of studies. Statistical analyses were conducted using STATA software (ver. 14.0). RESULTS: A total of 20 studies investigating 648 environmental V. cholerae O1/O139 isolates were analysed. The majority of the studies were originated from Asia (n = 9). In addition, a large number of studies (n = 15 i.e. 71.4%) included in the meta-analysis revealed the resistance to cotrimoxazole and ciprofloxacin. The WPR rates were as follows: cotrimoxazole 59%, erythromycin 28%, tetracycline 14%, doxycycline 5%, and ciprofloxacin 0%. There was increased resistance to nalidixic acid, cotrimoxazole, furazolidone, and tetracycline while a decreased resistance to amoxicillin, ciprofloxacin, erythromycin, chloramphenicol, ampicillin, streptomycin, and ceftriaxone was observed during the years 2000-2020. A significant decrease in the doxycycline and ciprofloxacin-resistance rates in V. cholerae O1/O139 isolates was reported over the years 2011-2020 which represents a decrease in 2001-2010 (p < 0.05). CONCLUSIONS: Fluoroquinolones, gentamicin, ceftriaxone, doxycycline, kanamycin, and cefotaxime showed the highest effectiveness and the lowest resistance rate. However, the main interest is the rise of antimicrobial resistance in V. cholerae strains especially in low-income countries or endemic areas, and therefore, continuous surveillance, careful appropriate AST, and limitation on improper antibiotic usage are crucial.

Varenicline limits ischemia reperfusion injury following testicular torsion in mice.

BACKGROUND: Torsion of the spermatic cord and the resulting testicular ischemia leads to the production of inflammatory cytokines and cell death due to impaired aerobic metabolism. Following reperfusion of the testis, a robust innate inflammatory response furthers tissue injury due to the production of reactive oxygen species and disruption of normal capillary function. Blunting the innate immune response with antioxidants, anti-inflammatory medications and targeted genetic interventions reduces long term testicular injury in animal models of torsion, however these approaches have limited clinical applicability. Mediated via α7 nACh receptors, the cholinergic anti-inflammatory pathway limits NFKB signaling and prevents renal fibrosis following warm renal ischemia. We identified varenicline as an FDA approved α7 nAChR agonist and hypothesized that varenicline administration would decrease long-term testicular atrophy and fibrosis in a murine model of testicular torsion. METHODS: Using an established model, unilateral testicular torsion was induced in mature male CD1 mice by rotating the right testicle 720° for 2 h. In the treatment group, 4 doses of varenicline (1mg/grm) were administered via intraperitoneal injection every 12 h, with the first dose given 1 h after the creation of testicular torsion. The acute inflammatory response was evaluated 48 h following reperfusion of the testis. Long term outcomes were evaluated 30 days following testicular perfusion. RESULTS: 48 h following reperfusion, the testis of animals treated with varenicline demonstrated a significant reduction in the inflammatory response as measured by the acute immune cell infiltrate, myeloperoxidase activity, concentration of reduced glutathione and expression of downstream NF-KB targets. 30 days following reperfusion, animals treated with varenicline, demonstrated decreased testicular atrophy (Summary Figure), fibrosis and expression of pro-fibrotic genes. CONCLUSION: Activation of a central immunosuppressive cascade with varenicline after the onset of testicular torsion reduces ischemia reperfusion injury and prevents long term testicular atrophy and fibrosis. Further studies are needed to define the optimum dose and varenicline administration regimen. Our results suggest that varenicline offers a novel, FDA approved, adjunct to the current management of testicular torsion.