In Vitro antibiotic combinations of Colistin, Meropenem, Amikacin, and Amoxicillin/clavulanate against multidrug-resistant Klebsiella pneumonia isolated from patients with ventilator-associated pneumonia.

BACKGROUND: Hospital infections such as ventilator-associated pneumonia (VAP) due to multidrug-resistant Klebsiella pneumoniae (MDR-KP) strains have increased worldwide. In addition, biofilm production by these resistant isolates has confronted clinicians with higher treatment failure and infection recurrence. Given the paucity of new agents and limited data on combination therapy for MDR-KPs, the present study sought to evaluate the in vitro activity of several antibiotic combinations against planktonic and biofilm MDR-KPs isolated from patients with VAP. RESULTS: All 10 carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates demonstrated multidrug resistance against the tested antibiotics. At planktonic mode, combinations of colistin-meropenem and amoxicillin/clavulanate in combination with meropenem, colistin, or amikacin showed synergism against 60-70% isolates. On the other hand, in the biofilm state, colistin-based combinations exhibited synergism against 50-70% isolates and the most effective combination was colistin-amikacin with 70% synergy. CONCLUSIONS: The results revealed that combinations of amoxicillin/clavulanate with colistin, meropenem, or amikacin in the planktonic mode and colistin with amoxicillin/clavulanate, meropenem, or amikacin in the biofilm mode could effectively inhibit CRKP isolates, and thus could be further explored for the treatment of CRKPs.

Determining effects of nitrate, arginine, and ferrous on antibiotic recalcitrance of clinical strains of Pseudomonas aeruginosa in biofilm-inspired alginate encapsulates.

BACKGROUND: Biofilms play a role in recalcitrance and treatability of bacterial infections, but majority of known antibiotic resistance mechanisms are biofilm-independent. Biofilms of Pseudomonas aeruginosa, especially in cystic fibrosis patients infected with the alginate producing strains in their lungs, are hard to treat. Changes in growth-related bacterial metabolism in biofilm affect their antibiotic recalcitrance which could be considered for new therapies designed based on these changes. In this study, effects of nitrate, arginine, and ferrous were investigated on antibiotic recalcitrance in alginate-encapsulated P. aeruginosa strains isolated from cystic fibrosis patients in the presence of amikacin, tobramycin, and ciprofloxacin. Also, expression of an efflux pump gene, mexY, was analyzed in selected strains in the presence of amikacin and ferrous. METHODS: Clinical P. aeruginosa strains were isolated from cystic fibrosis patients and minimum inhibitory concentration of amikacin, tobramycin, and ciprofloxacin was determined against all the strains. For each antibiotic, a susceptible and a resistant or an intermediate-resistant strain were selected, encapsulated into alginate beads, and subjected to minimal biofilm eradication concentration (MBEC) test. After determining MBECs, sub-MBEC concentrations (antibiotics at concentrations one level below the determined MBEC) for each antibiotic were selected and used to study the effects of nitrate, arginine, and ferrous on antibiotic recalcitrance of encapsulated strains. Effects of ferrous and amikacin on expression of the efflux pump gene, mexY, was studied on amikacin sensitive and intermediate-resistant strains. One-way ANOVA and t test were used as the statistical tests. RESULTS: According to the results, the supplements had a dose-related effect on decreasing the number of viable cells; maximal effect was noted with ferrous, as ferrous supplementation significantly increased biofilm susceptibility to both ciprofloxacin and amikacin in all strains, and to tobramycin in a resistant strain. Also, treating an amikacin-intermediate strain with amikacin increased the expression of mexY gene, which has a role in P. aeruginosa antibiotic recalcitrance, while treating the same strain with ferrous and amikacin significantly decreased the expression of mexY gene, which was a promising result. CONCLUSIONS: Our results support the possibility of using ferrous and arginine as an adjuvant to enhance the efficacy of conventional antimicrobial therapy of P. aeruginosa infections.

Molecular Characteristics of Staphylococcus aureus Strains Isolated from Nasal Cavity and Wound Infections Among Diabetic Patients.

Staphylococcus aureus is the most common pathogen contributing to diabetic foot infections (DFI). Nasal transmission of S. aureus potentially increases the risk of endogenous infection. The aim of this study was to determine the genetic diversity and antibiotic resistance profile of S. aureus isolates in nasal and wound samples from diabetic patients. A cross-sectional study was conducted from July 2018 to September 2019. S. aureus was isolated from the anterior nares and wounds of diabetic patients. All S. aureus isolates were characterized by detection of resistance and virulence genes (mecA, ermA, ermC, hla, hlb, hlg, sea, lukDE, pvl), staphylococcal cassette chromosome mec (SCCmec)-typing and staphylococcal protein A (spa)-typing. A total of 34 S. aureus were isolated from the wounds of 115 diabetic patients with DFI. Twenty-four S. aureus isolates were collected from the anterior nares of patients, and thirteen patients had concurrent S. aureus in nasal and wound specimens. The prevalence of methicillin-resistant S. aureus (MRSA) in nasal specimens was noticeable (41.7%), and the most common spa-type in nasal and wound specimens was t14870. Nearly half of the patients with concurrent S. aureus in wound and nasal specimens had similar isolates from both sites. Our data suggest that detection and screening of S. aureus colonization in the nasal cavity may prevent subsequent endogenous infections, particularly with MRSA strains.

Association between Probiotics and Modulation of Gut Microbial Community Composition in Colorectal Cancer Animal Models: A Systematic Review (2010-2021).

Background: Colorectal cancer (CRC) is one of the most prevalent gastrointestinal malignancies and is considered the third major cause of mortality globally. Probiotics have been shown to protect against the CRC cascade in numerous studies. Aims: The goal of this systematic review was to gather the preclinical studies that examined the impact of probiotics on the alteration of gut microbiota profiles (bacterial communities) and their link to colorectal carcinogenesis as well as the potential processes involved. Methods: The search was performed using Scopus, Web of Science, and PubMed databases. Five parameters were used to develop search filters: "probiotics," "prebiotics," "synbiotics," "colorectal cancer," and "animal model." Results: Of the 399 full texts that were screened, 33 original articles met the inclusion criteria. According to the current findings, probiotics/synbiotics could significantly attenuate aberrant crypt foci (ACF) formation, restore beneficial bacteria in the microbiota population, increase short-chain fatty acids (SCFAs), and change inflammatory marker expression. Conclusions: The present systematic review results indicate that probiotics could modulate the gut microbial composition and immune regulation to combat/inhibit CRC in preclinical models. However, where the evidence is more limited, it is critical to transfer preclinical research into clinical data.

Lactobacillus rhamnosus R0011 Treatment Enhanced Efficacy of Capecitabine against Colon Cancer in Male Balb/c Mice.

The microbiome of the intestinal system is well-known as a modulatory factor. Having a balanced status of microbiota could help to prevent diseases, especially cancers related to the gastrointestinal system. We investigated the effects of Lactobacillus rhamnosus (Lr) and capecitabine on tumor size and physiologic features, such as bodyweight, liver enzymes, and blood profile, in a subcutaneously induced cancer model using CT-26 murine colon carcinoma cells. We divided 48 male Balb/c inbred mice into six groups. Lr had been orally pre-inoculated to the mice for 14 day consecutively. CT-26 cells were implanted subcutaneously into the mice's flank. Following the injection of cancer cells, Lr was inoculated to the mice three times per week for four weeks. Capecitabine was inoculated in the third week after the induction of cancer. The tumor size was significantly decreased in treated groups in comparison to the cancer group (1174.5 ± 63.8, 1119.2 ± 86.3, and 985.6 ± 48 mm3 vs. 1674.2 ± 66 mm3, P < 0.0001). Data showed that Lr and capecitabine enhanced Bax/Bcl-2 ratio and caspase-3 level compared to cancer group (p < 0.0001). White blood cells (WBCs) were significantly decreased in the capecitabine group compared to probiotic group (P < 0.05). Measurement of bodyweight, liver enzymes, and interleukin-6 (IL-6) level showed that Lr, in addition to preventive and therapeutic effects, might have protective effects against chemotherapy side effects. Preventing WBCs' reduction, protecting mice from losing weight, induction of apoptosis, and enhancing the serum level of IL-6 indicated that Lr might be associated with better management of colorectal cancer and chemotherapy side effects.

Prevalence of Antibiotic-Resistant Lactobacilli in Sepsis Patients with Long-Term Antibiotic Therapy.

Lactobacilli are the most common probiotic bacteria found in the human gut microbiota, and the presence of acquired antibiotic resistance determinants carried on mobile genetic elements must be screened due to safety concerns. Unnecessary and inappropriate antibiotic therapy, as well as ingested antibiotic resistance bacteria (originating from food or food products), influence the abundance of antibiotic resistance genes in human guts, with serious clinical consequences. The current study looked into the antibiotic resistance of lactobacilli isolated from the guts of sepsis patients on long-term antibiotic therapy. The broth microdilution method was used to investigate the minimum inhibitory concentrations (MICs) of antibiotics such as imipenem, meropenem, erythromycin, tetracycline, cefepime, ciprofloxacin, and gentamycin, and the molecular genetic basis of resistance was studied based on the MIC values. The isolates were phenotypically resistant to tetracycline (20%), fluoroquinolone (20%), and macrolide (5%). Following that, resistance genes for tetracycline [tet(L), tet(O), tet(K), and tet(M)], macrolide [erm(B) and erm(C)], and beta-lactams [bla(CMY)] were investigated. Tetracycline or macrolide resistance genes were not found in the isolates, and only one isolate possessed the bla(CMY) resistance gene. The findings suggested that tetracycline and macrolide resistance may be linked to other resistance genes that were not investigated in this study. Because tetracyclines, fluoroquinolones, and macrolides are commonly used in clinics and animals, there has been concern about the spread of resistance in humans. If acquired antibiotic resistance is passed down through mobile genetic elements, it may serve as a reservoir of resistance for gut pathogens and other microbiome environments.

Frequency of Salmonella serotypes among children in Iran: antimicrobial susceptibility, biofilm formation, and virulence genes.

BACKGROUND/SIGNIFICANCE: Salmonella gastroenteritis causes significant morbidity among pediatric patients, mainly in developing world, such as the Middle East and North Africa (MENA) region. Concurrently, data from MENA countries like Iran, regarding prevalence of Salmonella serotypes, antimicrobial susceptibility, and biofilm production is scarce. MATERIAL & METHODS: Slide agglutination was used to determine the serogroup of 140 Salmonella isolates recovered from 4477 stool specimens collected from children with gastroenteritis, and isolates were serotyped by PCR assay. The antimicrobial susceptibility of isolates to five first line drugs was assessed by disk diffusion assay using CLSI guidelines. Semi-quantitative evaluation of biofilm production was done by microtiter plate assay followed by PCR detection of biofilm-associated virulence genes csgD, pefA, and bcsA for each isolate. RESULTS: Nearly 94% of Salmonella isolates were recovered from ≤ 5-year-old patients, and 99% of isolates were non-typhoidal. While we found extensive diversity among Salmonella isolates, serogroup D (46%) predominated, and Salmonella Enteritidis (41%) was the most common serotype that showed the highest antimicrobial susceptibility rate (> 96%). For the first time in Iran, S. Newport serotype from human specimens was isolated. Most isolates were sensitive to all test antimicrobials, but 35% of isolates were not-typed (NT) that showed the highest resistance with 48% being resistant to ≥ 1 test antimicrobial. Majority of isolates made weak (or no) biofilm, and we found a weak association between antimicrobial susceptibility, biofilm production, or virulence genes csgD, pefA, and bcsA. CONCLUSIONS: The most effective measure that may control pediatric salmonellosis outbreaks is raising awareness of parents of preschoolers about food safety. Isolation of highly diverse Salmonella serotypes, including many commonly isolated from animals, indicates widespread contamination of the food chain. Majority of serotypes were sensitive to first-line antimicrobials, thus presently, pediatric Salmonella infections in this region may be controlled by conventional antimicrobials. However, despite the current trend, an imminent emergence of resistant Salmonella strains is foreseen, since various serotypes resistant to > 1 antimicrobial agent are typically associated with animals. Our results warrant further investigation that includes correlation analysis of clinical data regarding treatment outcomes, and serotype attributes like virulence genes.

Distribution and Characteristics of Bacteria Isolated from Cystic Fibrosis Patients with Pulmonary Exacerbation.

Background: Cystic fibrosis (CF) is an inherited recessive disorder characterized by recurrent and persistent pulmonary infections, resulting in lung function deterioration and early mortality. Methods: A cross-sectional study was conducted on the bacterial profile and antibiotic resistance pattern of 103 respiratory specimens from CF patients with signs of pulmonary exacerbation. Antibiotic susceptibility testing and biofilm formation of Staphylococcus aureus and Pseudomonas aeruginosa isolates were performed by the Kirby-Bauer disc diffusion method and microtiter plate assay, respectively. Molecular typing of S. aureus and P. aeruginosa isolates was carried out by spa typing and repetitive extragenic palindromic element PCR. Results: In a total of 129 isolates, the most prevalent organisms were S. aureus (55.3%) and P. aeruginosa (41.7%). Other less prevalent bacterial isolates include coagulase-negative staphylococci, Escherichia coli, klebsiella spp., Enterobacter spp., and Achromobacter xylosoxidans. The highest rate of resistance for S. aureus was observed to azithromycin and erythromycin (80%), ciprofloxacin (52.3%), clindamycin (44.6%) and tetracycline (43%). Twenty percent of S. aureus isolates were methicillin-resistant S. aureus (MRSA) and 47.6% were MDR S. aureus. For P. aeruginosa isolates the highest resistance was to cefepime (38.3%) and levofloxacin (33.3%) and 20% showed MDR phenotype. Conclusion: Our study demonstrated a significant decline in the prevalence of P. aeruginosa infections in comparison to previous studies. We found S. aureus to be more prevalent in younger patients, whereas mucoid P. aeruginosa showed a shift in prevalence toward older ages. Molecular typing methods showed great diversity between isolates.

Probiotic Lactobacillus rhamnosus Supplementation Improved Capecitabine Protective Effect against Gastric Cancer Growth in Male BALB/c Mice.

The gastric cancer (GC) is biologically and genetically heterogeneous with a poorly understood carcinogenesis at the molecular level. Herein, we studied the effects of probiotics (Lactobacillus rhamnosus) on subcutaneous implantation of xenograft GC. Moreover, the effect of probiotics (L. rhamnosus) was compared with the capecitabine drug as known used drug against GC. Human GC tissue was obtained from patients with gastric adenocarcinoma and grafted into mice armpit. Probiotic (L. rhamnosus) was given to animals by gavage 2 weeks prior to GC and 4 weeks after GC induction. Also, capecitabine was orally added through feeding tube at the last week of treatment procedure. All grafted animals received cyclosporine a day before the surgery and during the study period to prevent graft rejection. Capecitabine-probiotic complex reduced the size of the axillary implanted GC when compared with control group. Furthermore, combination of capecitabine and probiotic increased apoptotic and necrotic responses in the grafted tumor, blood cells (red blood cells, white blood cells, and platelet counts) in comparison with capecitabine. Probiotic (L. rhamnosus) administration effectively improved the therapeutic index and outcomes, and also, improved the therapeutic effects of the capecitabine.

The role of nonautologous and autologous adipose-derived mesenchymal stem cell in acute pyelonephritis.

We compared the therapeutic effects of autologous and nonautologous adipose-derived mesenchymal stem cell (ADMSC), in ameliorating the renal function in a rabbit model of acute pyelonephritis. The difference of perirenal and neck subcutaneous ADMSCs were also evaluated. Twenty female rabbits were apportioned to 5 groups. In group I (n = 4), the rabbits were injected direct inoculation of Escherichia coli (E. coli) into the right kidney. In group II (n = 4), autologous ADMSCs obtained from nape adipose tissue were injected into the subcapsular space 1 week after E. coli injection, while nonautologous ADMSCs of the same origin (from male rabbits) were applied in group III (n = 4). In group IV (n = 4), autologous perirenal ADMSCs were applied with the same method, while perirenal nonautologous ADMSCs from male rabbits were used in group V (n = 4). Technetium-99m-DMSA renal scan was performed 1, 2 and 4 months post-injection in all groups. Kidneys were excised for the evaluation of histopathological changes in the same time points. PCR examination for detection of Y-chromosome (in group III and V) and fluorescent evaluation (in group II and IV) were also performed to determine the fate of injected cells. Injection of autologous ADMSCs resulted in more satisfactory outcomes in reduction of interstitial fibrosis, tubular, and glomerular atrophy as compared to nonautologous groups. However, histopathological ameliorations were significantly better in group IV in which autologous perirenal ADMSC was applied. Remarkably, two months after the injection, Technetium-99m-DMSA renal scan showed that right kidney reached to near normal cortical function (48 and 45%) in group IV and V, respectively as compared to groups II (41%) and III (37%). Autologous ADMSCs may have better results in cell therapy as compared to nonautologous cells. However, more satisfactory outcomes may be obtained when the cell source is selected from the surrounding adipose tissue.

Assessment and comparison of probiotic potential of four Lactobacillus species isolated from feces samples of Iranian infants.

The probiotic potential of Lactobacillus species isolated from infant feces was investigated. For this study, the antibiotic susceptibility, tolerance in gut-related conditions, antimicrobial activity, and ability to adhere to a human colorectal adenocarcinoma cell line (Caco-2 cells) of four common Lactobacillus species (Lactobacillus paracasei [n = 15], Lactobacillus rhamnosus [n = 45], Lactobacillus gasseri [n = 20] and Lactobacillus fermentum [n = 18]) were assessed. Most isolates that which were sensitive to imipenem, ampicillin, gentamycin, erythromycin and tetracycline were selected for other tests. L. gasseri isolates had the greatest sensitivity to gastric and intestinal fluids (<10% viability). L. fermentum (FH5, FH13 and FH18) had the highest adhesion to Caco-2 cells. The lowest antibacterial activity against pathogenic bacteria was shown by L. gasseri strains in spot tests. Furthermore, non-adjusted cell-free culture supernatants with low pH had greater antimicrobial activity, which was related to organic acid. The results showed that some isolates of L. rhamnosus and L. fermentum are suitable for use as a probiotic.

Investigation of EpsA, OmpA, and Bap Genes among MDR and XDR Acinetobacter baumannii Isolates in Khorramabad, Iran.

BACKGROUND: Acinetobacter baumannii is an opportunistic hospital pathogen with high antibiotic resistance, and the ability to produce biofilm. This study aimed to investigate epsA, ompA, and bap genes involved in biofilm formation in MDR and XDR clinical isolates of Acinetobacter baumannii in Khorramabad, Iran. METHODS: In this study, 79 A. baumannii isolates were collected from various samples of the patients admitted to tertiary hospitals in Khorramabad city, Iran, between January and August 2019. After performing the semi-quantitative evaluation of biofilm production by microtiter plate assay, screening of isolates carrying epsA, ompA, and bap genes was done by PCR method. Finally, statistical analyses were conducted using SPSS 22. RESULTS: Among 79 A. baumannii isolates, 52% XDR, 40% MDR, and 16% non-XDRMDR isolates were found to be biofilm producers. All XDR and 94% MDR isolates had ompA and epsA genes, and bap genes were detected among > 80% of these isolates. Moreover, the presence of biofilm-related genes and biofilm production among non-XDRMDR isolates were less than among resistant isolates (p≤ 0.01). CONCLUSION: Based on the results, biofilm production and simultaneous presence of epsA, ompA, and bap genes among MDR, and XDR A. baumannii isolates have been found to be significantly more than non-XDR-MDR isolates.

A five-year systematic review and meta-analysis study on methicillin resistant Staphylococcus epidermidis strains in Iran.

Background and Objectives: One of the most prevalent drug-resistant bacteria is methicillin-resistant Staphylococcus epidermidis (MRSE) causing healthcare infections. Previously, a meta-analysis study on the frequency of MRSE was conducted from Mar 2006 to Jan 2016 in Iran. The present study aimed to evaluate the changes in this prevalence in the last 5 years in different cities in Iran. Materials and Methods: Published articles on the frequency of MRSE were collected from the Web of Science, PubMed, Scopus, Google Scholar, Cochrane Library, and Iranian databases from the beginning of 2016 to the end of 2020. Of the 503 records identified, 17 studies met the inclusion criteria, and their extracted data were analyzed using comprehensive meta-analysis version 2.0 (Biostat). Results: The analysis showed that the frequency of MRSE has decreased significantly in the last five years and reached 60.8 [95% confidence interval (95% CI) 54.2-66.9] among culture-positive cases of S. epidermidis in Iran. Conclusion: The noticeable reduction in the prevalence of MRSE in Iran could be due to the improvement of infection control programs and interruption of the pathogen transmission cycle. Another influential reason is the significant reduction in methicillin prescriptions by physicians for infections caused by staphylococci.

Characterization of the resistome in Lactobacillus genomic sequences from the human gut.

OBJECTIVES: The gut is a complex environment inhabited by a wide range of bacterial species. Lactobacillus species constitute a significant proportion of this environment and, due to their mobile genetic elements such as plasmids and transposons, are more likely to acquire and transfer antibiotic resistance genes through horizontal gene transfer (HGT). METHODS: The current study obtained and analysed 321 genome assemblies to determine the prevalence of intrinsic and acquired antibiotic resistance genes (ARGs) among Lactobacillus species colonizing the human gastrointestinal tract. RESULTS: A total of four high-frequency resistance genes were identified, including dfra42 (42%), poxtA (17.4%), lmrB (12%), and BJP-1 (7.7%); aside from dfra42, which is an intrinsic resistance gene, the other genes are acquired resistance genes. PoxtA was found in several different species, mainly in L. paracasei, whereas BJP-1 and lmrB were found in only one species, L. rhamnosus. IS5-like elements family transposase flanked 11% and 8% of detected lmrB and BJP-1, respectively, while a variety of insertion sequences surrounded 22% of identified poxtA. Furthermore, to the best of our knowledge, this is the first report of BJP-1 in lactobacilli that would suggest it has transferred from soil microbiota to humans. CONCLUSION: According to the 'One Health' perspective, early detection of a new reservoir would control the global spread of the antibiotic-resistant bacterial species among the three environments, which include humans, the environment, and animals. Finally, the study's findings may then highlight the possibility of lactobacilli acquiring or transmitting resistance to other species within or outside the human intestine.

Multiplex high-resolution melting assay for simultaneous detection of five key bacterial pathogens in urinary tract infections: A pilot study.

The diagnosis of urinary tract infections (UTIs) is usually based on the results of urine culture, but it is time-consuming, labor-intensive and has a low sensitivity. The aim of this study was to develop multiplex high-resolution melting assay (MHRM) for the simultaneous detection of five common bacterial pathogens (Escherichia coli, Klebsiella pneumoniae, Staphylococcus saprophyticus, Enterococcus faecalis, and group B streptococci (GBS)) directly from urine samples. A total of 287 urine specimens were evaluated by HRM assay and the results were compared with the conventional culture method. Five different melt curves generated and differentiated five bacterial pathogens. The detection limit of the MHRM assay was 1.5 × 103 CFU/ml for E. coli and K. pneumoniae and 1.5 × 102 CFU/ml for S. saprophyticus, E. faecalis and GBS. Compared to culture, the specificity of the MHRM assay ranged from 99.3 to 100%, and sensitivity 100% for all test pathogens. The MHRM assay developed in the current study might be functional tool for the diagnosis of UTIs and has the potential for direct detection of the organism in the clinical samples. Additionally, it creates results in less than 5 h, helping clinicians to start treatment with appropriate antimicrobial agents. This method could be a useful supplement to urine culture.

Chitosan Scaffold Containing Periostin Enhances Sternum Bone Healing and Decreases Serum Level of TNF-α and IL-6 after Sternotomy in Rat.

BACKGROUND: In the aftermath of bone injuries, such as cranium and sternum, bone wax (BW) is used to control bleeding from the bone surfaces during surgery. Made up of artificial substances, however, it is associated with many complications such as inflammation, increased risk for infection, and bone repair delay. We, therefore, in this study set out to design and evaluate a novel BW without the above-mentioned side-effects reported for other therapies. METHODS: The pastes (new BW(s)) were prepared in the laboratory and examined by MTT, MIC, MBC, and degradability tests. Then, 60 adult male Wistar rats, divided into six equal groups including chitosan (CT), CT-octacalcium phosphate (OCP), CT-periostin (Post), CT-OCP-Post, Control (Ctrl), and BW, underwent sternotomy surgery. Once the surgeries were completed, the bone repair was assessed radiologically and thereafter clinically in vivo and in vitro using CT-scan, H&E, ELISA, and qRT-PCR. RESULTS: All pastes displayed antibacterial properties and the CT-Post group had the highest cell viability compared to the control group. In contrast to the BW, CT-Post group demonstrated weight changes in the degradability test. In the CT-Post group, more number of osteocyte cells, high trabeculae percentage, and the least fibrous connective tissue were observed compared to other groups. Additionally, in comparison to the CT and Ctrl groups, higher alkaline phosphatase activity, as well as decreased level of serum tumor necrosis factor-α, interleukin-6, and OCN in the CT-Post group was evident. Finally, Runx2, OPG, and RANKL genes' expression was significantly higher in the CT-Post group than in other groups. CONCLUSION: Our results provide insights into the desirability of pastes in terms of cellular viability, degradability, antibacterial properties, and surgical site restoration compared to the BW group. Besides, Periostin could enhance the osteogenic properties of bone tissue defect site.

Phenotypic and genotypic evaluation of fluoroquinolone resistance in clinical isolates of Staphylococcus aureus in Tehran.

BACKGROUND: Fluoroquinolones are broad-spectrum antibiotics widely used in the treatment of bacterial infections such as Staphylococcus aureus isolates. Resistance to these antibiotics is increasing. MATERIAL/METHODS: The occurrence of mutations in the grlA and gyrA loci were evaluated in 69 fluoroquinolone-resistant S. aureus isolates from 2 teaching hospitals of Tehran University of Medical Sciences. RESULTS: Out of the 165 S. aureus isolates, 87 (52.7%) were resistant to methicillin and 69 (41.8%) were resistant to fluoroquinolone. Fluoroquinolone-resistant S. aureus isolates had a mutation at codon 80 in the grlA gene and different mutational combinations in the gyrA gene. These mutational combinations included 45 isolates at codons 84 and 86, 23 isolates at codons 84, 86 and 106 and 1 isolate at codons 84, 86 and 90. Fluoroquinolone-resistant S. aureus isolates were clustered into 33 PFGE types. CONCLUSIONS: The findings of this study show that the fluoroquinolone-resistant S. aureus strains isolated in the teaching hospitals in Tehran had multiple mutations in the QRDRs region of both grlA and gyrA genes.

Molecular investigation of Staphylococcus aureus isolated from the patients, personnel, air and environment of an ICU in a hospital in Tehran.

BACKGROUND: The aim of this study was to determine the prevalence and characteristics of Staphylococcus aureus isolates from the patients, staff, air and environments of an ICU in a hospital in Tehran. MATERIALS AND METHODS: During this study, 37 S. aureus isolates were collected and analyzed via the spa typing method. RESULTS: Of the 37 S. aureus isolates, 35 (94%) were methicillin resistant (MRSA), 28 (76%) were identified as SCCmec types III or IIIA, four (10%) were identified as SCCmec types I or IA and three (8%) were identified a SCCmec type IV. All of the MRSA isolates were resistant to oxacillin and contained mecA. The isolates were all spa typed and found to comprise 11 spa types, including t7688, t7689, and t7789, which have not previously been reported. The spa type t7688 was isolated from the hands of two ICU personnel. The spa type t7689 was observed among five isolates from the air and the environment. The spa type t7789 was observed among three isolates from the patients, ventilators and the air. The majority of the isolates (43%) belonged to spa types t030 and t037. CONCLUSION: Our results revealed that MRSA strains that were isolated from the air, the environment of the ICU and the patients who were colonized or infected with MRSA often exhibited the same spa and SCCmec types. These results also reveal that the isolates from the patients and environment were usually indistinguishable.

Characterization of AmpC, CTX-M and MBLs types of ß-lactamases in clinical isolates of Klebsiella pneumoniae and Escherichia coli producing Extended Spectrum ß-lactamases in Kerman, Iran.

BACKGROUND: Extended spectrum ß-lactamases (ESBLs) and AmpC ß-lactamases enzyme are major sources of resistance to ß-lactam antibiotics especially in Enterobacteriaceae such as Escherichia coli and Klebsiella pneumoniae. Increasing frequency of the co-existence of ESBLs with AmpC-ß-lactamases in bacteria is a serious threat for treating bacterial infections. OBJECTIVES: The aim of this study was to determine the presence of AmpC and CTX-M types of ß-lactamases in clinical isolates of E. coli and K. pneumoniae producing ESBLs. MATERIALS AND METHODS: Resistance to different antibiotics was determined using the standard disk diffusion method. ESBLs, MBLs and AmpC-ß-lactamases were detected by the combination double disk test (CDDT) method and polymerase chain reaction (PCR) was used to determine bla CTX -M genes in the ESBLs and AmpC positive isolates. RESULTS: The prevalence of ESBLs and AmpC-ß-lactamase producer isolates was 181 (43.8%) and 133 (37.2%), respectively. The prevalence of bla CTX -M among isolates was 61 (14.7%). CONCLUSIONS: Outbreak of isolates co-expressing AmpC-ß-lactamases and ESBLs can cause serious problems in the future, regarding the treatment of infections caused by these common enteric pathogens.

Viral etiology of acute lower respiratory tract infections in hospitalized young children in a children's referral hospital in Iran.

Viruses are considered major causes of acute respiratory tract infections among children under 5 years old. In this study we investigated the prevalence of three respiratory viruses--respiratory syncytial virus (RSV), influenza virus (INF) and adenovirus (ADV)--among hospitalized children with acute viral lower respiratory tract infections (LRTIs). Nasopharyngeal aspirates were collected from children under five who had been hospitalized for LRTIs. The clinical data, including demographic data (age and sex), vital symptoms and signs at admission, duration of fever, duration of hospitalization, chest X-ray findings and outcome were considered. All inpatient specimens were tested by reverse transcriptase-polymerase chain reaction (RT-PCR) for RSV and the INF-A, INF-B and parainfluenza viruses and by polymerase chain reaction (PCR) for ADV. Out of those from 232 patients, 58 (25%) specimens were positive for either RSV, INF or ADV. The most predominant pathogens were RSV (40 cases, 17.2%), followed by INF (10 cases, 4%; including 8 type A and 2 type B) and ADV (8 cases, 3.4%). A total of 32 (55.1%) viral cases were identified in the spring, followed by 19 (32.7%) in the autumn and 7 (12%) in the winter. There was no significant correlation between clinical symptoms and the individual virus detected. In our study, RSV and INF were the two most common causes of LRTIs. These data are helpful for guiding the development of further vaccines as well as the use of antiviral drugs. Further studies will be needed to investigate other respiratory viruses such as parainfluenza, human metapneumovirus and rhinovirus.