Risk factors for mortality in hospitalized patients infected with carbapenem-resistant Pseudomonas aeruginosa in Iran.

Introduction: Mortality due to carbapenem-resistant Pseudomonas aeruginosa (CRPA) infection has increased worldwide in recent years. The risk factors associated with hospital settings in Iran and the role of strain resistance mechanisms in many studies are unclear. Methods: A retrospective study was conducted on consecutive non-repetitive patients with CRPA infections isolated from seven major hospitals from northwest of Iran. We evaluated different risk factors and characteristics of bacteria for the death or survival of patients. Results: In this study, 116 CRPA isolates were obtained from patients admitted to seven hospitals. Forty-one (35.3%) patients were enrolled in the study of mortality risk factors. Significant risk factors associated with mortality included the site of infection, hospitalization in different wards, the use of invasive devices, and the type of carbapenem resistance mechanisms. Conclusions: ICU admission, the use of mechanical ventilation and chest tube and infection with pandrug-resistant strains were the most important factors in increasing mortality due to CRPA infection. These results suggested that the clinicians should emphasize the proper use of antibiotic and invasive procedures.

Association of specific haplotype of tumor necrosis factor-α and interleukin-1ß polymorphisms with Helicobacter pylori infection and gastric carcinogenesis.

INTRODUCTION: The Helicobacter pylori infection and cytokine-mediated inflammatory responses play significant roles in the pathogenesis of gastric cancer (GC). This study was performed to determine the association between the risk of GC and genetic polymorphisms in interleukin (IL)-1ß and tumor necrosis factor-alpha (TNF-α). METHODS: The polymorphisms of IL-1ß and TNF-α genes were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 290 patients who underwent endoscopy. Infection with H. pylori was diagnosed by histological analysis, rapid urease test, and PCR of gastric biopsy samples. Quantitative real-time PCR was performed to determine the relative mRNA expression levels. RESULTS: No significant difference was detected in allele frequency and genotype of all studied polymorphisms between chronic gastritis (CG), GC and healthy individuals. IL-1ß mRNA was down-regulated in both gastritis (relative quantification (RQ)=0.447) and the GC groups (RQ=0.151). In contrast, the expression of TNF-α was up-regulated in the GC group (RQ=2.817) compared to the gastritis group (RQ=0.861). CONCLUSIONS: The studied single-nucleotide polymorphisms are not risk factors for development of CG and GC. However, H. pylori infection causes a huge increase in the TNF-α expression in GC patients.

Prevalence, Risk Factors, and Epidemiology of Food-borne Botulism in Iran.

BACKGROUND: Botulism is a severe neuroparalytic disease caused by toxins produced by several Clostridium species. This work presents the surveillance results of botulism in Iran, with the distribution of the cases by regions and by vehicle of transmission. METHODS: We describe the findings of the Centers for Disease Control and Prevention (CDC) surveillance on 2037 suspected cases of food-borne botulism during 2007-2017. RESULTS: A total of 252 (12.3%) cases were confirmed to food-borne botulism. The mean annual incidence per 100,000 Iranian Natives was 7.1 cases for male individuals and 3.3 cases for female individuals. All botulism events were confirmed to be foodborne. The most commonly implicated food was home-prepared traditional processed fish product, followed by the consumption of commercially canned products and non-pasteurized dairy products. Forty-eight (19%) fatal botulism were reported which, the case-fatality rate declined from 4.5% to 0.7% during the study period. CONCLUSION: Laboratory-based diagnosis of botulism is an imperative procedure to elucidate cases, particularly food-borne botulism, to identify toxins in food and confirm clinical diagnosis, helping sanitary control measures. In addition, educational materials related to botulism prevention should be disseminated to different communities.

Molecular mechanisms related to colistin resistance in Enterobacteriaceae.

Colistin is an effective antibiotic for treatment of most multidrug-resistant Gram-negative bacteria. It is used currently as a last-line drug for infections due to severe Gram-negative bacteria followed by an increase in resistance among Gram-negative bacteria. Colistin resistance is considered a serious problem, due to a lack of alternative antibiotics. Some bacteria, including Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacteriaceae members, such as Escherichia coli, Salmonella spp., and Klebsiella spp. have an acquired resistance against colistin. However, other bacteria, including Serratia spp., Proteus spp. and Burkholderia spp. are naturally resistant to this antibiotic. In addition, clinicians should be alert to the possibility of colistin resistance among multidrug-resistant bacteria and development through mutation or adaptation mechanisms. Rapidly emerging bacterial resistance has made it harder for us to rely completely on the discovery of new antibiotics; therefore, we need to have logical approaches to use old antibiotics, such as colistin. This review presents current knowledge about the different mechanisms of colistin resistance.

Trends in the discovery of new drugs for Mycobacterium tuberculosis therapy with a glance at resistance.

Despite the low expensive and effective four-drug treatment regimen (isoniazid, rifampicin, pyrazinamide and ethambutol) was introduced 40 years ago, TB continues to cause considerable morbidity and mortality worldwide. In 2015, the WHO estimated a total of 10.4 million new tuberculosis (TB) cases worldwide. Currently, the increased number of multidrug-resistant (MDR-TB), extensively-drug resistant (XDR-TB) and in some recent reports, totally drug-resistant TB (TDR-TB) cases raises concerns about this disease. MDR-TB and XDR-TB have lower cure rates and higher mortality levels due to treatment problems. Novel drugs and regimens for all forms of TB have emerged in recent years. Moreover, scientific interest has recently increased in the field of host-directed therapies (HDTs) in order to identify new treatments for MDR-TB. In this review, we offer an update on the discovery of new drugs for TB therapy with a glance at molecular mechanisms leading to drug resistance in Mycobacterium tuberculosis.

EXTENDED-SPECTRUM BETA-LACTAMASE PRODUCING GRAM NEGATIVE BACTERIA IN IRAN: A REVIEW.

BACKGROUND: The emergence and spread of extended spectrum ß-lactamase (ESBL)-producing Gram- negative bacteria (GNB), particularly in Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa, have increased all over the world. ESBLs are characterized by their ability to hydrolyze ß-lactams, early cephalosporins, oxyimino-thiazolyl cephalosporins, and monobactams, but not cephamycins or carbapenems. The rate of nosocomial infections caused by ESBL-producing GNB in Asia Pacific has increased and several studies have identified their prevalence in the region. The aim of this study is to review the prevalence of ESBL-producing GNB in the West Asia and the Middle East with a particular focus on Iran. MATERIALS AND METHODS: The available evidence from various studies (Microbia and clinical studies, retrieved from the PubMed, and Scopus databases) regarding the ESBL producing Gram negative bacteria in Iran were evaluated. RESULTS: In almost all parts of the country, high resistance has been observed, especially in the central part of Iran. Up to 89.8% Escherichia coli, 72.1% Klebsiella pneumonia, 84.2% Acinetobacter baumannii, and 83.8% Pseudomonas aeruginosa isolates are ESBL positive. CONCLUSION: The present study showed the increasing prevalence of ESBLs in different regions of Iran, which could be useful to strategic policy towards reducing reduce their prevalence.

The Prevalence of CTX-M-15 Extended-spectrum ß-Lactamases Among Salmonella spp. and Shigella spp. Isolated from three Iranian Hospitals.

Bacterial antimicrobial resistance mediated by the production of extended-spectrum ß-lactamases (ESBLs) is considered a major threat for treatment of Salmonella and Shigella infections. This study aimed to investigate antibiotic resistance patterns of Salmonella and Shigella spp. and presence of CTX-M from three teaching hospitals in Iran. In the present study, 58 clinical Shigella and 91 Salmonella isolates were recovered between 2009 and 2013 from 3 teaching hospitals in Iran. After culture and antimicrobial susceptibility testing, ESBL-positive isolates were subjected to further investigations. These included polymerase chain reaction (PCR) amplification and DNA sequencing of blaCTX-M-15 encoding plasmid. In both genera, high sensitivity to gentamicin and amikacin, but high resistance to ampicillin, tetracycline, and trimethoprim-sulfamethoxazole, was found. Molecular investigation showed that 31.8% isolates of Salmonella spp. and 34.48% isolates of Shigella spp. were CTX-M positive and all of them were also positive for ISEcpI. Protein translation, comparing with reference sequences, showed that all CTX-M isolates belong to CTX-M-15. The present study suggests that the resistance of ESBLs-producing Salmonella and Shigella spp. in Iran hospitals is very serious. Therefore, strategies to minimize the spread of ESBL-producing isolates should be implemented.

Epidemiology of multidrug-resistant Acinetobacter baumannii strains in Iran: a systematic review and meta-analysis.

Acinetobacter baumannii is an important opportunistic pathogen that causes major public health concern especially in hospitalized patients due to the acquisition of multidrug resistance (MDR). The aim of this study was to systematically review published data about the prevalence rate of MDR-A. baumannii (MDR-AB) from different parts of Iran and provide an overall relative frequency (RF) using meta-analysis. All available national and international databanks were searched to find published studies up to June 2016. Quality of studies was assessed by STROB and PRISMA forms. Because of the significant heterogeneity observed, random effects model was used to combine the results. STATA SE version 11.2 was used for statistical analysis. Out of the 9646 results, 37 suitable articles were extracted according to inclusion and exlusion criteria. The pooled prevalence of MDR-AB was estimated 72% annually. Relative frequency of MDR-AB in different studies varied from 22.8 to 100%. Since the prevalence of MDR-AB is higher than many other countries, measures should be taken to keep the emergence and transmission of these strains to a minimum.

CTX-M extended-spectrum ß-lactamase-producing Klebsiella spp, Salmonella spp, Shigella spp and Escherichia coli isolates in Iranian hospitals

Abstract This study was conducted in Iran in order to assess the distribution of CTX-M type ESBLs producing Enterobacteriaceae. From January 2012 to December 2013, totally 198 E. coli, 139 Klebsiella spp, 54 Salmonella spp and 52 Shigella spp from seven hospitals of six provinces in Iran were screened for resistance to extended-spectrum cephalosporins. After identification and susceptibility testing, isolates presenting multiple-drug resistance (MDR) were evaluated for ESBL production by the disk combination method and by Etest using (cefotaxime and cefotaxime plus clavulanic acid). All isolates were also screened for bla CTX-M using conventional PCR. A total of 42.92%, 33.81%, 14.81% and 7.69% of the E. coli, Klebsiella spp, Salmonella spp and Shigella spp isolates were MDR, respectively. The presence of CTX-M enzyme among ESBL-producing isolates was 85.18%, 77.7%, 50%, and 66.7%, in E. coli, Klebsiella spp, Salmonella spp and Shigella spp respectively. The overall presence of CTX-M genes in Enterobacteriaceae was 15.4% and among the resistant isolates was 47.6%. This study indicated that resistance to β-lactams mediated by CTX-M enzymes in Iran had similar pattern as in other parts of the world. In order to control the spread of resistance, comprehensive studies and programs are needed.

CTX-M extended-spectrum ß-lactamase-producing Klebsiella spp, Salmonella spp, Shigella spp and Escherichia coli isolates in Iranian hospitals.

This study was conducted in Iran in order to assess the distribution of CTX-M type ESBLs producing Enterobacteriaceae. From January 2012 to December 2013, totally 198 E. coli, 139 Klebsiella spp, 54 Salmonella spp and 52 Shigella spp from seven hospitals of six provinces in Iran were screened for resistance to extended-spectrum cephalosporins. After identification and susceptibility testing, isolates presenting multiple-drug resistance (MDR) were evaluated for ESBL production by the disk combination method and by Etest using (cefotaxime and cefotaxime plus clavulanic acid). All isolates were also screened for blaCTX-M using conventional PCR. A total of 42.92%, 33.81%, 14.81% and 7.69% of the E. coli, Klebsiella spp, Salmonella spp and Shigella spp isolates were MDR, respectively. The presence of CTX-M enzyme among ESBL-producing isolates was 85.18%, 77.7%, 50%, and 66.7%, in E. coli, Klebsiella spp, Salmonella spp and Shigella spp respectively. The overall presence of CTX-M genes in Enterobacteriaceae was 15.4% and among the resistant isolates was 47.6%. This study indicated that resistance to ß-lactams mediated by CTX-M enzymes in Iran had similar pattern as in other parts of the world. In order to control the spread of resistance, comprehensive studies and programs are needed.

Low intensity ultrasound increases the fermentation efficiency of Lactobacillus casei subsp.casei ATTC 39392.

L-Lactic acid (L-LA) is one of the microbial products with several applications and its production efficiency is so important. In the present study, we have been exploring application of low intensity ultrasound technology to improve the metabolic activity for L-lactic acid production by Lactobacillus casei in different mediums. L-LA, biomass production and substrate (protein) consumption were measured as parameters of fermentation yield. L-LA and protein contents were determined using the titratable acidity and the biuret method respectively. Spectrophotometry (OD600nm) was used for measuring cell growths. L-LA, biomass production and protein consumption considered as dependent variables, but the amplitude of waves (20%, 40% and 60%), waves duration (15, 30, 45 s) and add of peptone (2, 6 and 10 g/l) as independent variables. The results showed that L-LA, biomass production and substrate consumption significantly increased (≈25%). Optimum conditions for biomass production was amplitude of 60%, 15s exposure time and 10 g/l peptone, while for acid lactic production and substrate consumption was 40%, 30s and 6g/l peptone, respectively. Flowcytometry analysis also showed that sonication led to increasing cell membrane permeability. This observation shows low intensity ultrasound as a potential parameter in the improvement of metabolic activity of L. casei.

Current methods for the identification of carbapenemases.

Detection of carbapenemases in clinical microbiology labs is a challenging issue. Comparison of the results of susceptibility testing with the breakpoint values of carbapenems is the first step in the screening of carbapenemase producers. To date, screening of carbapenemase-producing (CP) bacteria has been mostly performed by a selective medium. Although these media are practical for the detection of most CP isolates, the inoculated plates have to be incubated overnight. Subsequently, we need the confirmation of the carbapenemase producers present in the culture medium by additional testing [e.g. inhibition studies with liquid or solid media, modified Hodge test (MHT), or gradient strips], which can take up to another 48 hours. Despite the lack of discrimination between the three different classes of carbapenemases (KPC, MBL and OXA) and difficulties in the interpretation of the results, the MHT is usually deemed as the phenotypic reference method for the confirmation of carbapenemase production. Molecular techniques, such as real-time polymerase chain reaction (PCR) assays, in contrast to phenotypic methods that are very time consuming, are faster and allow for the quick identification of carbapenemase genes. These techniques can detect and characterize carbapenemases, including NDM- and KPC-mediated resistance, which is critical for epidemiological investigations. The aim of this review is to gather a summary of the available methods for carbapenemase detection and describe the strengths and weaknesses of each method.

Viral infections in patients with acute respiratory infection in Northwest of Iran.

INTRODUCTION: Acute respiratory infection (ARI) is one of the main causes of morbidity and mortality all around the world. The aim of this study was to determine the frequency, mortality and association with clinical entities of influenza virus type A, influenza virus type B, respiratory syncytial virus (RSV), coronavirus, and adenoviruses in patients with ARI. MATERIALS AND METHODS: During September 2014 till May 2015, 143 respiratory inpatients samples for viral testing collected from central Hospital in Northwest of Iran. A real-time reverse transcription-PCR (RT-PCR) assay was done to allow in one test the detection of influenza A and B viruses. Also, RSV and adenovirus were identified by Immunochromatography test. RESULTS: Twenty-four (46%) cases were positive for influenza A, which 11 (46%) of them were subtype H1N1 and 13 (54%) cases were subtype H3N2. Also, 21 (40%) cases were positive for influenza B, 5 (10%) cases were positive for RSV, and 2 (4%) cases were positive for adenovirus. One of the patients was positive for both influenza A and adenovirus. Two of the patients were positive for both influenza A and RSV. None of the patients were positive for coronavirus. CONCLUSIONS: Our findings show the importance of influenza virus type A, influenza virus type B, RSV, and adenoviruses associated with ARI in hospitalized patient and the different epidemiological patterns of the viruses in Tabriz, Iran.

Colistin, mechanisms and prevalence of resistance.

BACKGROUND: Infections caused by multi-drug-resistant Gram-negative bacteria, particularly Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae, that cause nosocomial infections, represent a growing problem worldwide. The rapid increase in the prevalence of Gram-negative pathogens that are resistant to fluoroquinolones and aminoglycosides as well as all ß-lactams, including carbapenems, monobactam, cephalosporins and broad-spectrum penicillins, has prompted the reconsideration of colistin as a valid therapeutic option. Colistin is an old class of cationic, which act by disrupting the bacterial membranes resulting in cellular death. Although there has been a significant recent increase in the data gathered on colistin, focusing on its chemistry, antibacterial activity, mechanism of action and resistance, pharmacokinetics, pharmacodynamics and new clinical application, the prevalence of colistin resistance has been very little reported in the literature. This review concentrates on recent literature aimed at optimizing the clinical use of this important antibiotic. METHODS: The available evidence from various studies (microbiological and clinical studies, retrieved from the PubMed, and Scopus databases) regarding the mechanisms and prevalence of resistance was evaluated. RESULTS: Increasing use of colistin for treatment of infections caused by these bacteria has led to the emergence of colistin resistance in several countries worldwide. Although resistance to polymyxins is generally less than 10%, it is higher in the Mediterranean and South-East Asia (Korea and Singapore), where colistin resistance rates are continually increasing. CONCLUSION: There is a critical need for effective infection prevention and control measures and strict use of antibiotics in the world to control the rise and spread of colistin resistance.