The effect of polyclonal and monoclonal based antibodies as promising potential therapy for treatment of sepsis: A systematic review.

While mortality caused by sepsis remains an unsolved problem, studies showed conflicting results about effectiveness of monoclonal and polyclonal antibodies in patients suffering sepsis. For this reason, this current study provides an update of review clinical randomized trial studies until March 2024. The main object of this study is to determine effects of monoclonal and polyclonal antibodies on mortality rate and hospitalization of patients suffering sepsis. Search of Scopus, Web of science, EMBASE, PubMed and Cochrane were performed and randomized controlled trials which conducted in patients with septic shock or bacterial sepsis were included. Two reviewers assessed all searched trials for eligibility according to already defined criteria and did data collection and analyses afterwards. Present study showed monoclonal and polyclonal antibodies are a safe strategy with mild-to-moderate adverse effects. However, most studies indicate no significant change among inter-and intra-group comparison (p > 0.05) and further studies are needed, results showed an increase in survival rate, ventilator-and ICU-free days, resolve organ dysfunction, mediating inflammation related cytokines.

Prevalence and epidemiological investigation of mgrB-dependent colistin resistance in extensively drug resistant Klebsiella pneumoniae in Iran.

Carbapenemases-producing K. pneumoniae are challenging antimicrobial therapy of hospitalised patients, which is further complicated by colistin resistance. The aim of this study was to investigate the molecular epidemiological insights into carbapenemases-producing and colistin-resistant clinical K. pneumoniaeA total of 162 colistin resistant clinical strains of K. pneumoniae were collected during 2017-2019. Antimicrobial susceptibility and the colistin minimum inhibitory concentration were determined. Using PCR assay, the prevalence of resistance-associated genes including blaKPC, blaIMP, blaVIM, blaOXA-48, blaNDM-1 and mcr-1 to -9 was examined. Additionally, a PCR assay was used to examine the mgrB gene in colistin-resistant bacteria. 94.4% of the tested strains were resistant to imipenem and 96.3% were resistant to meropenem. Colistin resistance (MIC > 4 µg/L) was observed in 161 isolates (99.4%) by Colistin Broth Disk Elution method. The KPC enzyme was the most common carbapenemase and was identified in 95 strains (58.6%), followed by the IMP, VIM and OXA-48 detected in 47 (29%), 23 (14.2%) and 12 (7.4%) isolates, respectively. However, no NDM-1 gene was detected. Additionally, none of the studied isolates harbored mcr variants, while mgrB gene was observed in 152 (92.6%) isolates. Colistin resistance of K. pneumoniae isolates may be associated with mgrB gene mutation. To stop the spread of resistant K. pneumoniae, surveillance must be improved, infection prevention protocols must be followed, and antibiotic stewardship must be practised.

Molecular characterization of carbapenem-resistant Pseudomonas aeruginosa isolated from four medical centres in Iran.

BACKGROUND: Understanding the mechanisms of antibiotic resistance is important for designing new therapeutic options and controlling resistant strains. The goal of this study was to look at the molecular epidemiology and mechanisms of resistance in carbapenem-resistant Pseudomonas aeruginosa (CRPA) isolates from Tabriz, Iran. METHODS: One hundred and forty P. aeruginosa were isolated and antibiotic susceptibility patterns were determined. Overproduction of AmpC and efflux pumps were discovered using phenotypic techniques. Polymerase chain reaction (PCR) was used to determine the presence of carbapenemase-encoding genes. In addition, the expressions of OprD and efflux pumps were evaluated by the Real-Time PCR. Random amplified polymorphic DNA typing (RAPD) was performed for genotyping. RESULTS: Among 140 P. aeruginosa isolates, 74 (52.8%) were screened as CRPA. Overexpression of efflux systems was observed in 81% of isolates, followed by decreased expression of OprD (62.2%), presence of carbapenemase genes (14.8%), and overproduction of AmpC (13.5%). In most isolates, carbapenem resistance was multifactorial (60.8%). According to our results, the prevalence of CRPA is at alarming levels. Overexpression of efflux systems was the most common mechanism of carbapenem resistance. CONCLUSION: Most isolates may originate in patients themselves, but cross-infection is possible. Therefore, we suggest a pattern shift in the strategy of CRPA in our setting.

Passive immunization with anti- chimeric protein PilQ/PilA -DSL region IgY does not protect against mortality associated with Pseudomonas aeruginosa sepsis in a rabbit model.

BACKGROUND: Pseudomonas aeruginosa sepsis is associated with unacceptably high mortality and, for many of those who survive, long-term morbidity. The aims of this study were to production of IgY against chimeric protein pilQ-pilA-DSL region and killed- whole cell Pseudomonas aeruginosa O1 (PAO1) strain and their efficacy for immunoprophylaxis of sepsis caused by P. aeruginosa in a rabbit model. METHODS: Specific IgY was obtained by immunization of hens. The purity of IgY was determined by SDS-PAGE analysis. The effect of IgY on growth and hydrophobicity of P. aeruginosa were performed through time-kill assay and microbial adhesion to hydrocarbons test (MATH), respectively. The efficacy of specific IgYs was examined against P. aeruginosa sepsis in a rabbit model. The rabbits were monitored for 72 h to record physiological characters and survival. Hematologic factors, C-reactive protein, pro-inflammatory cytokines, and bacterial count from blood and solid organs were measured, periodically. RESULTS: We found that the growth inhibitory effect of the anti- killed whole cell IgY was higher than anti-pilQ-pilA IgY (P < 0.001). The hydrophobicity effect of PAO1 increased when bacteria were opsonized by anti- killed whole cell IgY while the hydrophobicity activity was decreased following incubation of PAO1 with anti-pilQ-pilA IgY in a broth medium (P < 0.001). Following intravenous (IV) administration of produced IgYs, no significant difference was observed in the survival, decrease in inflammatory mediators and clinical symptoms between the groups 48h post infection (P > 0.05). Moreover, no considerable decrease was observed in the bacterial load of blood, lungs and kidneys in rabbits treated with specific IgYs and control groups (P > 0.05). No bacteria were found in the spleen and liver samples from infected rabbits. CONCLUSION: Although produced IgYs had a good immunoreactivity, IV immunization of IgYs was not protective against P. aeruginosa sepsis in the rabbit model. Further studies are needed to assess the immune response and decreasing mortality rate using the rabbit sepsis model.

Monoclonal antibody directed to the PilQ -PilA DSL region in Pseudomonas aeruginosa improves survival of infected mice with antibiotic combination.

The infections caused by Pseudomonas aeruginosa are related to high mortality and morbidity in critically ill patients because of multidrug resistance. Thus, we performed the efficacy of the monoclonal antibody (mAb) against PilQ -PilA DSL region (QA) in combination with antibiotics in a model of P. aeruginosa infection. In the present study, three clinically applicable antibiotics (levofloxacin, ceftazidime and gentamicin) and the anti-QA mAb were utilized for treatment of P. aeruginosa sepsis in mice. Reliably, in comparison with other treatment groups (antibody or antibiotic administration), the combination of antibiotic and anti-QA mAb essentially enhanced the survival of mice infected with P. aeruginosa PAO1. This synergistic effect was due to improved bactericidal effect, which prevented bacterial dissemination to different organs. Consequently, the antibiotic and anti-QA mAb combination gives a new effective strategy for the treatment of P. aeruginosa sepsis, particularly when large numbers of exceptionally virulent strains are present.

Expression of RND efflux pumps mediated antibiotic resistance in Pseudomonas aeruginosa clinical strains.

Resistance-Nodulation-Division (RND) efflux pumps are responsible for multidrug resistance in Pseudomonas aeruginosa. The present study aimed to evaluate the overexpression of RND efflux pumps and its role in the antibiotic resistance of P. aeruginosa clinical isolates. A number of 122 isolates were obtained from three military hospitals in Tehran, Iran. In order to determine the antibiotic resistance, the isolates were identified and assessed by the disk diffusion and agar dilution methods. This study investigated the gene expression of four multi-drug efflux pump systems (MexAB-OprM, MexCD-OprJ, MexEF-OprN and MexXY (-OprA)) and its correlation with antibiotic resistance. The isolates indicated that the highest resistance rate was against ticarcillin (80%), followed by ciprofloxacin (74%) and meropenem (71%). Most of them expressed mexB (69%), mexC (28.7%), mexE (43.4%), and mexY (74.6%), suggesting that mexB and mexY were highly expressed in the studied strains. The overexpression of mexB and mexY was significantly more prevalent in the ICU wards (p = 0.033). Furthermore, there was a significant correlation between the expression of RND-type efflux pumps and the resistance to most anti-pseudomonal antibiotics.

Therapeutic bacteria to combat cancer; current advances, challenges, and opportunities.

Successful treatment of cancer remains a challenge, due to the unique pathophysiology of solid tumors, and the predictable emergence of resistance. Traditional methods for cancer therapy including radiotherapy, chemotherapy, and immunotherapy all have their own limitations. A novel approach is bacteriotherapy, either used alone, or in combination with conventional methods, has shown a positive effect on regression of tumors and inhibition of metastasis. Bacteria-assisted tumor-targeted therapy used as therapeutic/gene/drug delivery vehicles has great promise in the treatment of tumors. The use of bacteria only, or in combination with conventional methods was found to be effective in some experimental models of cancer (tumor regression and increased survival rate). In this article, we reviewed the major advantages, challenges, and prospective directions for combinations of bacteria with conventional methods for tumor therapy.

Prevalence and antimicrobial susceptibility pattern of toxigenic Clostridium difficilestrains isolated in Iran

Background/aim: Clostridium difficile is a frequent cause of nosocomial infections and has become a major public health concern in developed nations. In the present study, the prevalence and antimicrobial susceptibility pattern of toxigenic C. difficile strains isolated in Iran were investigated. Materials and methods: Between June 2016 and May 2017, 2947 inpatient fecal samples were taken from symptomatic adult hospitalized patients in different units of 32 care facilities in Tehran, Iran. C. difficile strains were identified by microbiological/biochemical methods. Susceptibility to 20 antimicrobials was measured by E-test method. Toxin-specific immunoassays and cytotoxicity assays were used to determine in vitro toxin production Results: Out of 2947 fecal samples, 538 (18.25%) C. difficile isolates were obtained among those with suspected CDI. In E-test method, all C. difficile isolates were susceptible to fidaxomicin, vancomycin, amoxicillin/clavulanate, and meropenem and were resistant to penicillin G. The prevalence of multidrug resistant C. difficile was 69.33% (373/538). Among 538 C. difficile, 147 (27.32%), 169 (31.41%), and 222 (41.26%) isolates were TcdA+/TcdB+, TcdA-/TcdB+, and TcdA-/TcdB-, respectively Conclusion: The results evidently support the hypothesis of a probable role of toxigenic strains of C. difficile in developing gastrointestinal complaints in patients with diarrhea

Fosfomycin: mechanisms and the increasing prevalence of resistance.

There are challenges regarding increased global rates of microbial resistance and the emergence of new mechanisms that result in microorganisms becoming resistant to antimicrobial drugs. Fosfomycin is a broad-spectrum bactericidal antibiotic effective against Gram-negative and certain Gram-positive bacteria, such as Staphylococci, that interfere with cell wall synthesis. During the last 40 years, fosfomycin has been evaluated in a wide range of applications and fields. Although numerous studies have been done in this area, there remains limited information regarding the prevalence of resistance. Therefore, in this review, we focus on the available data concerning the mechanisms and increasing resistance regarding fosfomycin.

Epidemiological burden of Listeria monocytogenes in Iran.

OBJECTIVES: Listeria monocytogenes is a foodborne pathogenic bacteria causing the infection listeriosis, which possibly affects all people, particularly immunocompromised persons and pregnant women. This microorganism can be found in several processed foods, dairy products, raw milk, meat and fish products, seafoods, eggs, fruits, and vegetables. This review discusses about the epidemiological significance, incidence, contamination routes of L. monocytogenes in different products and current data about listeriosis in the Iran. MATERIALS AND METHODS: For accessing to relevant articles and studies, a search was done in main databases and also, almost all Iranian published articles were studied in this field. RESULTS: Outbreaks of listeriosis have been reported in many parts of the worldwide, however there is scanty data about the prevalence of listeriosis in Iran. Accordingly, as a result of high incidence of L. monocytogenes in women with bad obstetric history or history of abortions, diagnosis procedures for detection of L. monocytogenes and timely treatment was suggested. CONCLUSION: In spite of low incidence of infection in the past, increased interest for lightly preserved and/or ready-to-eat (RTE) food products has recently led to increasing of L. monocytogenes prevalence which has become a public health concern. Subsequently, further researches about the prevalence of L. monocytogenes and also antibiotic susceptibility testing is needed to enable the detection of the contaminated foods, as well as ensures the effective treatment.

Assessing the prevalence of Staphylococcus aureus in infertile male patients in Tabriz, northwest Iran.

BACKGROUND: Staphylococcus aureus is an infrequent, but one of the most successful bacteria that associated with infertility and are able to spermatozoa immobilization and agglutination. OBJECTIVE: The aim of present study was to determine the frequency of S. aureus in semen obtained from infertile male patients in northwest Iran. MATERIALS AND METHODS: Seminal fluids of 100 infertile men were evaluated. Standard semen examination was done according to World Health Organization guidelines. After isolation and identification of S. aureus isolates according to reference methods, determination of susceptibility against important antibiotics and polymerase chain reaction were performed to identify mecA and tst genes. RESULTS: Data obtained from the present study shows that 16% of infertile male patients were colonized by S. aureus. Ten (62.5%) of the individuals had abnormal seminal fluid sperm motility and morphology and three (18.8%) of them had an abnormal seminal fluid density, whereas after washing with albumin-saline declined to 5 (31.3%), 4 (25%) and 1 (6.3%), respectively. The antibiogram results showed that, except penicillin, other antibiotics have high activity on isolates. Regarding polymerase chain reaction results, mecA sequences were detected in 3 (18.7%) strains, whilst the tst gene encoding TSST-1 was not detected in any of clinical strains. CONCLUSION: It would appear that the S. aureus may be an additional negative factor worsening sperm quality and affecting male fertility. Therefore, it demands that all the patients attending in infertility treatment facilities be investigated thoroughly.

Extraction and purification of the H9N2 virus nucleoprotein: A simple and practical method.

Background: Avian Influenza disease annually entails a significant economic loss to the poultry industry around the world. Influenza virus is a polymorphic virus of the orthomyxoviridae family (single-stranded RNA genome), and nucleoprotein (NP) is the structural and internal protein of the virus. The aim of the work was to purify nucleoprotein for further investigations with a simple, low-cost, fast and practical method. Methods: In this study, H9N2 influenza virus was isolated in specific pathogen-free embryonated chicken eggs by allantoically inoculating 103 to 105 egg-infective doses (EID50) for 9 to 11 days, purified by 10% (W/V) polyethylene glycol (PEG) 6000 with a sucrose gradient of 60% to 30%. The influenza virus proteins were collected and prepared as fractions by preparative electrophoresis. Finally, the purified NP was subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot procedures. Results: The protein analysis with SDS-PAGE and silver nitrate staining indicated that the desired samples contained purified nucleoprotein and lacked other viral proteins. The results of the investigation of lyophilized fractions containing nucleoprotein on the SDS-PAGE revealed the absence of viral RNA in nucleoprotein and its high purity. Conclusion: According to this study, purified nucleoprotein can be used to produce nucleoprotein vaccines, as well as to study structural, molecular and diagnostic and therapeutic materials.

A simple route for preparation of pH-sensitive hydrogels by using egg white proteins in alginate scaffold for the encapsulation of probiotics / Ruta sencilla para la preparación de hidrogeles sensibles al pH mediante el uso de proteínas de clara huevo en soporte de alginato para la encapsulación de probióticos

Aims: In the present study, we evaluated the use of egg white proteins in alginate scaffolds and calcium alginate for the formulation of Lactobacillus casei and Lactobacillus acidophilus in the stomach acidic conditions. Material and Methods: after microorganism’s encapsulation in egg white proteins in alginate, survival assays and release in different conditions were evaluated. Scanning electron microscope and Fourier-transform infrared spectroscopy were used for analysis. Results: The results showed the high potential of this type of formulation in protecting the probiotics from stomach acidic conditions that is due to the significant increase in survival of the bacteria. Our study showed that the viability of the L. casei to free L. acidophilus had much less, however, with the encapsulation of the bacteria Egg white proteins in Alginate increased their survival significantly. Specially for the L. casei. Swelling and shrinkage behavior of egg white proteins in alginate capsules in different pH showed that the swelling of the capsule in the distilled water in the neutral terms had more inflation capacity than similar position in terms of gastric acidity. Conclusions: the use of egg white proteins-Alginate for encapsulation of probiotics enhanced the stability of these microorganisms in simulated gastric environments adverse conditions

Objetivos: En el presente trabajo se comparó el uso de proteínas de clara de huevo en soporte de alginato y alginato de calcio para la formulación. Material y Métodos: Tras la encapsulación de microorganismos en proteínas de clara de huevo en alginato, se evaluaron ensayos de supervivencia y liberación en diferentes condiciones. Para el análisis se han utilizado la microscopio electrónico con escáner y la espectroscopia infrarroja de transformada de Fourier. Resultados: Los resultados muestran el alto potencial de este tipo de formulación en la protección de los probióticos frente a las condiciones ácidas del estómago, por el aumento significativo en la supervivencia de las bacterias. Nuestro estudio demostró que la viabilidad de L. casei y L. acidophilus era mucho menor, sin embargo, con la encapsulación de las bacterias con proteínas de clara de huevo en alginato aumentaron significativamente su supervivencia especialmente para L. casei. La hinchazón y el comportamiento de contracción de las proteínas de clara de huevo en cápsulas de alginato en diferentes pH mostraron que la hinchazón de la cápsula en el agua destilada en términos neutros tenía más capacidad de inflación que una posición similar en términos de acidez gástrica. Conclusión: el uso de proteínas de clara de huevo-alginato para la encapsulación de probióticos mejora la estabilidad de estos microorganismos en condiciones adversas simuladas del medio gástrico

Linezolid: a promising option in the treatment of Gram-positives.

Linezolid, an oxazolidinone antimicrobial agent that acts by inhibiting protein synthesis in a unique fashion, is used in the treatment of community-acquired pneumonia, skin and soft-tissue infections and other infections caused by Gram-positive bacteria including VRE and methicillin-resistant staphylococci. Currently, linezolid resistance among these pathogens remains low, commonly <1.0%, although the prevalence of antibiotic resistance is increasing in many countries. Therefore, the development of resistance by clinical isolates should prompt increased attention of clinical laboratories to routinely perform linezolid susceptibility testing for this important agent and should be taken into account when considering its therapeutic use. Considering the importance of linezolid in the treatment of infections caused by Gram-positive bacteria, this review was undertaken to optimize the clinical use of this antibiotic.

Survey of the Antibiofilm and Antimicrobial Effects of Zingiber officinale (in Vitro Study).

BACKGROUND: Candidiasis is one of the most prevalent and important opportunistic fungal infections of the oral cavity caused by Candida yeast species like Candida albicans, C. glabrata, and C. krusei. In addition, several bacteria can cause oral infections. The inhibition of microbial biofilm is the best way to prevent oral infections. OBJECTIVES: The aim of the present study is to evaluate the antifungal, antimicrobial, and anti-biofilm properties of ginger (Zingiber officinale) extract against Candida species and some bacterial pathogens and the extract's effects on biofilm formation. MATERIALS AND METHODS: Ginger ethanolic extract as a potential mouthwash was used to evaluate its effect against fungi and bacteria using the microdilution method, and biofilm was evaluated using the crystal violet staining method and dead/alive staining. MTT assay was used to evaluate the possible cytotoxicity effects of the extract. RESULTS: The minimum inhibitory concentrations (MICs) of ginger extract for evaluated strains were 40, 40, 20, 20, 20, 20, 10, and 5 mg/mL for Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Bacillus cereus, Acinetobacter baumannii, C. albicans, and C. krusei, respectively. Ginger extract successfully inhibited biofilm formation by A. baumannii, B. cereus, C. krusei, and C. albicans. MTT assay revealed no significant reduction in cell viability after 24 hours. The minimum inhibitory biofilm concentrations (MIBCs) of ginger extract for fungi strains (C. krusei and C. albicans) were greater than those of fluconazole and nystatin (P = 0.000). CONCLUSIONS: The findings of the present study indicate that ginger extract has good antifungal and antibiofilm formation by fungi against C. albicans and C. Krusei. Concentrations between 0.625 mg/mL and 5 mg/mL had the highest antibiofilm and antifungal effects. Perhaps, the use of herbal extracts such as ginger represents a new era for antimicrobial therapy after developing antibiotic resistance in microbes.

Bacterial etiology and antibiotic susceptibility pattern of diabetic foot infections in Tabriz, Iran.

AIM: The aim of this study was to investigate anaerobic and aerobic bacteria profile and determination of antibiotic susceptibility pattern in aerobic bacteria. METHOD: Specimens were cultured using optimal aerobic and anaerobic microbiological techniques. Identification of bacterial isolates was performed by standard microbiological methods and antibiotic susceptibility testing was performed according to the guidelines of Clinical and Laboratory Standards Institute (CLSI). RESULT: 92 bacterial strains were isolated from 60 samples of diabetic foot ulcers. Predominant aerobic bacteria isolated from these infections were S. aureus (28%) followed by Enterobacteriaceae family (24%) including Escherichia coli (15%), Citrobacter spp. (4%), Enterobacter spp. (4%), and coagulase-negative Staphylococcus spp. (17%), Enterococcus spp. (15%), Pseudomonas aeruginosa (7%) and Acinetobacter spp. (4%). No Clostridium spp. were isolated and 4% Bacteroides fragilis obtained from anaerobic culture. All Gram-positive isolates were susceptible to linezolid while all Enterobacteriaceae showed sensitivity to imipenem. CONCLUSION: Most of DFIs specimens were poly microbial infection and predominant bacteria were S. aureus and B. fragilis. These wounds may require use of combined antimicrobial therapy for initial management.

Dissemination of carbapenemases producing Gram negative bacteria in the Middle East.

The emergence and spread of carbapenemase-producing bacteria, that hydolyze most ß-lactams, including carbapenems, are a major concern of public health system worldwide, particularly in the Middle East area. Since the plasmids harboring resistance genes could be spread across other bacterial populations, detection of carbapenemase-producing organisms has become more problematic. These organisms produce different types of enzymes including the most prevalent types including KPC, VIM, IMP, NDM, and OXA-48. Carbapenemase producers are mostly identified among Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii. This study reviewed almost all papers, which conducted in the Middle East. In order to decrease the spread of resistance, the regional cooperation has been emphasized by the Middle East countries. The highest resistance, which is mediated by KPC has been observed in Afghanistan, Saudi Arabia and Jordan followed by NDM in Pakistan and OXA in Turkey and Pakistan. It is important to mention that the spread of these types have been reported sporadically in the other countries of this area. This review described the widespread carbapenemases in the Middle East area, which have been identified in an alarming rate.