Risk factors and treatment outcome of smear positive pulmonary tuberculosis patients: A five-year study in the North of Iran.

Background: It is essential to constantly review the risk factors and treatment outcomes of tuberculosis (TB). This study evaluated some important risk factors of TB over five years. Methods: Between 2013 and 2018, all available information and possible risk factors related to TB patients were analyzed from the TB registry program of the health district of Gorgan, Iran. Results: Among 349 TB patients, 194 (55.59%) were males and 167 (47.85%) had at least a comorbidity. The death rate was higher in the age group more than 65 years (p < 0.001), the low-educated group (P = 0.012), and patients with underlying diseases, especially diabetes (p < 0.001). In total, univariate and multivariate statistical analyzes showed that having comorbidity (OR = 4.34; 95% CI 1.49 - 13.49), as well as, being jobless (OR = 3.07; 95% CI 1.19 - 8.59) were the main factors influencing the adverse events. Conclusion: According to the study, aging, underlying diseases, and cultural poverty include a higher share of the main risk factors for active TB and/or treatment outcomes. By considering these risk factors and training the medical staff continually, we can reduce the time of TB diagnosis, and prevent it from spreading.

Differential privacy preserved federated learning for prognostic modeling in COVID-19 patients using large multi-institutional chest CT dataset.

BACKGROUND: Notwithstanding the encouraging results of previous studies reporting on the efficiency of deep learning (DL) in COVID-19 prognostication, clinical adoption of the developed methodology still needs to be improved. To overcome this limitation, we set out to predict the prognosis of a large multi-institutional cohort of patients with COVID-19 using a DL-based model. PURPOSE: This study aimed to evaluate the performance of deep privacy-preserving federated learning (DPFL) in predicting COVID-19 outcomes using chest CT images. METHODS: After applying inclusion and exclusion criteria, 3055 patients from 19 centers, including 1599 alive and 1456 deceased, were enrolled in this study. Data from all centers were split (randomly with stratification respective to each center and class) into a training/validation set (70%/10%) and a hold-out test set (20%). For the DL model, feature extraction was performed on 2D slices, and averaging was performed at the final layer to construct a 3D model for each scan. The DensNet model was used for feature extraction. The model was developed using centralized and FL approaches. For FL, we employed DPFL approaches. Membership inference attack was also evaluated in the FL strategy. For model evaluation, different metrics were reported in the hold-out test sets. In addition, models trained in two scenarios, centralized and FL, were compared using the DeLong test for statistical differences. RESULTS: The centralized model achieved an accuracy of 0.76, while the DPFL model had an accuracy of 0.75. Both the centralized and DPFL models achieved a specificity of 0.77. The centralized model achieved a sensitivity of 0.74, while the DPFL model had a sensitivity of 0.73. A mean AUC of 0.82 and 0.81 with 95% confidence intervals of (95% CI: 0.79-0.85) and (95% CI: 0.77-0.84) were achieved by the centralized model and the DPFL model, respectively. The DeLong test did not prove statistically significant differences between the two models (p-value = 0.98). The AUC values for the inference attacks fluctuate between 0.49 and 0.51, with an average of 0.50 ± 0.003 and 95% CI for the mean AUC of 0.500 to 0.501. CONCLUSION: The performance of the proposed model was comparable to centralized models while operating on large and heterogeneous multi-institutional datasets. In addition, the model was resistant to inference attacks, ensuring the privacy of shared data during the training process.

Anesthesia and analgesia for common research models of adult mice.

Anesthesia and analgesia are major components of many interventional studies on laboratory animals. However, various studies have shown improper reporting or use of anesthetics/analgesics in research proposals and published articles. In many cases, it seems "anesthesia" and "analgesia" are used interchangeably, while they are referring to two different concepts. Not only this is an unethical practice, but also it may be one of the reasons for the proven suboptimal quality of many animal researches. This is a widespread problem among investigations on various species of animals. However, it could be imagined that it may be more prevalent for the most common species of laboratory animals, such as the laboratory mice. In this review, proper anesthetic/analgesic methods for routine procedures on laboratory mice are discussed. We considered the available literature and critically reviewed their anesthetic/analgesic methods. Detailed dosing and pharmacological information for the relevant drugs are provided and some of the drugs' side effects are discussed. This paper provides the necessary data for an informed choice of anesthetic/analgesic methods in some routine procedures on laboratory mice.

Evaluation of Mutations Related to Streptomycin Resistance in Mycobacterium tuberculosis Clinical Isolates.

Drug resistance to streptomycin in the clinical isolates of Mycobacterium tuberculosis (MTB) needs special consideration. It can mostly be caused by mutations in four genes with the names rpsL, rrs, gidB, and whiB7. The main objective of this study was the evaluation of the type and frequency of mutations in these mentioned genes using the PCR-sequencing method. This study was performed on 15 streptomycin-resistant and five streptomycin-sensitive isolates. Among resistant isolates, 11 samples contained mutations in codon 43 of the rpsL gene, which caused the lysine to be converted to arginine. Additionally, all of the isolates had mutations in the gidB. Missense mutations in codons 92 and 20 of this gene result in the amino acids Glutamic acid or Arginine being changed to Aspartic acid or Proline, respectively. No mutations in the rrs or whiB7 were found in any of the samples. Simultaneous mutations of rpsL and gidB were found in 10 isolates, the majority of which were Beijing strain. The results showed that the mutations of rpsL and gidB genes are mostly responsible for the streptomycin resistance in the evaluated MTB isolates. Furthermore, the discovery of dual mutations in Beijing strains highlights the strain's considerable potential for developing Tuberculosis drug resistance.

COVID-19 prognostic modeling using CT radiomic features and machine learning algorithms: Analysis of a multi-institutional dataset of 14,339 patients.

BACKGROUND: We aimed to analyze the prognostic power of CT-based radiomics models using data of 14,339 COVID-19 patients. METHODS: Whole lung segmentations were performed automatically using a deep learning-based model to extract 107 intensity and texture radiomics features. We used four feature selection algorithms and seven classifiers. We evaluated the models using ten different splitting and cross-validation strategies, including non-harmonized and ComBat-harmonized datasets. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were reported. RESULTS: In the test dataset (4,301) consisting of CT and/or RT-PCR positive cases, AUC, sensitivity, and specificity of 0.83 ± 0.01 (CI95%: 0.81-0.85), 0.81, and 0.72, respectively, were obtained by ANOVA feature selector + Random Forest (RF) classifier. Similar results were achieved in RT-PCR-only positive test sets (3,644). In ComBat harmonized dataset, Relief feature selector + RF classifier resulted in the highest performance of AUC, reaching 0.83 ± 0.01 (CI95%: 0.81-0.85), with a sensitivity and specificity of 0.77 and 0.74, respectively. ComBat harmonization did not depict statistically significant improvement compared to a non-harmonized dataset. In leave-one-center-out, the combination of ANOVA feature selector and RF classifier resulted in the highest performance. CONCLUSION: Lung CT radiomics features can be used for robust prognostic modeling of COVID-19. The predictive power of the proposed CT radiomics model is more reliable when using a large multicentric heterogeneous dataset, and may be used prospectively in clinical setting to manage COVID-19 patients.

Clinical Presentations of the Survivor and Non-survivor Hospitalized Patients with COVID-19 in the Golestan Province of Iran during the First Peak of the Epidemics.

Background: Considering the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, which causes coronavirus disease 2019 (COVID-19), we aimed to report the clinical features of 427 patients with COVID-19 and the outcomes after one-month admission to major teaching hospitals in the northeast of Iran. Materials and Methods: Data of patients hospitalized with COVID-19 from 20 February 2020 to 20 April 2020 was analyzed using the R software. The cases and their outcomes were monitored up to one month following their admission. Results: Among 427 patients with a median age of 53 years (50.8% male), 81 (19%) were directly admitted to the ICU ward, and 68 (16%) died during the study. The mean (SD) lengths of hospital stay were significantly higher in the non-survivors (6 (9) days) than survivors (4 (5) days) (P = 0.018). Ventilation need was reported in 67.6% of the non-survivors and 0.8% of the survivors (P < 0.001). Cough (72.8%), fever (69.3%), and dyspnea (64.0%) were the most common symptoms. There were more comorbidities in the severe cases (73.5%) and non-survivor (77.5%). Liver and kidney damage were significantly more common in non-survivors. Ninety percent of the patients had at least one abnormal chest CT scan finding, including crazy paving and consolidation patterns (27.1%), followed by the ground-glass opacity (24.7%). Conclusion: Results showed that the patients' age, underlying comorbidities, levels of SpO2, and laboratory findings at the time of admission may predict the progress of the disease and can be considered mortality-related factors.

Study on antibiotic resistance and phylogenetic comparison of avian-pathogenic Escherichia coli (APEC) and uropathogenic Escherichia coli (UPEC) isolates.

Avian pathogenic Escherichia coli (APEC) and uropathogenic E. coli (UPEC) can cause vast infections in humans and poultry. The present study was conducted to compare the isolates of the APEC and UPEC pathotypes on the basis phenotypic and genotypic features of antibiotic resistance and phylogenetic differences. Total number of 70 identified E. coli strains, including 35 APEC and 35 UPEC isolates, were isolated from avian colibacillosis and human urinary tract infection (UTI), and were subjected to the antimicrobial susceptibility testing, polymerase chain reaction (PCR) detection of the resistance genes, phylogenetic grouping and DNA fingerprinting with enterobacterial repetitive intergenic consensus PCR (ERIC - PCR) to survey the variability of the isolates. The most resistance rates among all E. coli isolates were, respectively, obtained for Ampicillin (84.20%) and sulfamethoxazole-trimethoprim (65.70%). The APEC and UPEC isolates showed the most susceptibility to imipenem and gentamycin, respectively. Among 70 APEC and UPEC isolates 34.20%, 32.80%, 20.00%, and 12.80% belonged to the A, B2, D, and B1 phylogenetic groups, respectively. Analysis of the DNA fingerprinting phylogenetic tree showed 10 specific clusters of APEC and UPEC isolates. According to the results, the most effective antibiotics and the phenotypic and genotypic predominant resistance patterns of the APEC and UPEC isolates were different. Moreover, APECs and UPECs showed various dominant phylogenetic groups. With all descriptions, the APEC isolates still are potential candidates for carrying important resistance genes and can be one of the possible strains related to human infections.

Epidemiological and clinical characteristics of the COVID-19 epidemic and associated factors for mortality in Golestan province, Iran: a retrospective cohort study.

BACKGROUND: We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia and risk factors associated for mortality. METHODS: In this study, we included inpatient with acute respiratory distress syndrome at Golestan Hospitals who had been discharged or had died in 2020. Epidemiological, and clinical data were extracted from electronic medical records and compared between recovered and died cases. We used multiple logistic regression methods to explore the risk factors associated with in-hospital death. RESULTS: Overall 2,835 acute respiratory distress syndrome patients were included in this study, and 874 (30.83%) were positive for 2019-nCoV. Five hundred and sixty-three patients (19.86%) died, 1,687 patients (59.51%) were recovered. Of the total deaths, only 288 (10.15%) were attributed to COVID-19. The most common symptoms at onset of illness were respiratory distress [1,795 (63.32%)], fever [1,601 (56.47%)], dry cough [1,595 (56.26%)], sore throat [445 (15.70%)], and myalgia [342 (12.06%)]. One thousand and twelve (35.7%) had 1 or more coexisting medical conditions. In multiple logistic regression analysis, risk factors associated with the death included older age [OR (Odds Ratio) = 1.03; 95% CI; 1.02-1.04], blood oxygen level (SPO2 < 93%) (OR = 2.44; 95% CI; 1.79-3.31), comorbidities (OR = 2.15; 95% CI; 1.62-2.84), respiratory distress (OR = 1.74; 95% CI; 1.28-2.37), and headache (OR = 0.44 95% CI; 0.21-0.92). CONCLUSIONS: The 2019-nCoV infection caused collections of severe respiratory illness and was associated to a high ratio of hospitalization in ICU and high mortality. Older age and comorbidities were associated with more risk of death among patients with 2019-nCoV.

Occurrence and risk factors of nontuberculous mycobacteria in tuberculosis-suspected patients in the north of Iran.

BACKGROUND AND OBJECTIVES: Some Nontuberculous Mycobacteria (NTM) can occasionally infect the human population and cause infections having symptoms similar to tuberculosis (TB). This study tried to provide updated data about the frequency and diversity of NTM species. MATERIALS AND METHODS: Suspicious samples of Mycobacterium tuberculosis (MTB) with both positive results in Ziehl-Neelsen (ZN) staining and Löwenstein-Jensen medium culturing were evaluated during January 2016 and December 2018 in Gorgan, Iran. After determination of MTB isolates by the growth rate, pigmentation status, the niacin test, and the insertion sequence 6110 (IS6110) PCR assay, other unknown isolates (presumably NTM) were detected by the 16S rDNA sequencing method and drawing the phylogenetic tree. Based on the patients' demographic information, their risk factors were also assessed. RESULTS: Among 226 culture-positive samples, obtained from 2994 individuals with suspected symptoms of TB, the analyses found 12 (5.3%) NTM and three Mycobacterium caprae isolates. Mycobacterium simiae (6/12) was the most prevalent NTM species. The average nucleotide similarity value was 98.2% ± 3.7. In comparison to patients with MTB (211 confirmed cases), other mycobacterium infections were more common in patients over 65 years old (Odd ratio (95% convenience interval): 2.96 (0.69 - 12.59), P = 0.14). CONCLUSION: Although the NTM species has a small portion in TB suspected patients, their prevalence has increased, mainly in elderly patients. Moreover, M. simiae was the most prevalent NTM species in our region. Therefore, identification of common species in each region is recommended and clinicians should pay more attention to them in each region.

Mycobacterium tuberculosis typing using Allele-specific oligonucleotide multiplex PCR (ASO-PCR) method.

Mycobacterium tuberculosis (M. tuberculosis) genotyping provides valuable information related to the origin and the evolution of the isolates. This study aimed to evaluate the applicability of single-nucleotide polymorphisms (SNPs) technique for lineages identification of M. tuberculosis and compare it with mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) method. The lineages of 162 clinically isolates were evaluated using six pair primers by Multiplex-PCR based on SNPs. Among 162 isolates, 70 (43.2%) isolates were lineage 4, following that 62 (38.3%) and 22 (13.6%) isolates were lineage 3 and 2, respectively. The method could not type 8 (4.9%) isolates. Moreover, we could identify 71 out of 79 unknown isolates resulted from the MIRU-VNTR method. The results showed that the SNP typing method has the potential to determine the lineages of M. tuberculosis as a rapid laboratory screening test.

Antimicrobials and Food-Related Stresses as Selective Factors for Antibiotic Resistance along the Farm to Fork Continuum.

Antimicrobial resistance (AMR) is a global problem and there has been growing concern associated with its widespread along the animal-human-environment interface. The farm-to-fork continuum was highlighted as a possible reservoir of AMR, and a hotspot for the emergence and spread of AMR. However, the extent of the role of non-antibiotic antimicrobials and other food-related stresses as selective factors is still in need of clarification. This review addresses the use of non-antibiotic stressors, such as antimicrobials, food-processing treatments, or even novel approaches to ensure food safety, as potential drivers for resistance to clinically relevant antibiotics. The co-selection and cross-adaptation events are covered, which may induce a decreased susceptibility of foodborne bacteria to antibiotics. Although the available studies address the complexity involved in these phenomena, further studies are needed to help better understand the real risk of using food-chain-related stressors, and possibly to allow the establishment of early warnings of potential resistance mechanisms.

A systematic review and meta-analysis for association of Helicobacter pylori colonization and celiac disease.

BACKGROUND AND OBJECTIVES: Based on some previous observational studies, there is a theory that suggests a potential relationship between Helicobacter pylori (H. pylori) colonization and celiac disease (CeD); however, the type of this relationship is still controversial. Therefore, we aimed to conduct a systematic review and meta-analysis to explore all related primary studies to find any possible association between CeD and human H. pylori colonization. DATA SOURCES: Studies were systematically searched and collected from four databases and different types of gray literature to cover all available evidence. After screening, the quality and risk of bias assessment of the selected articles were evaluated. SYNTHESIS METHODS: Meta-analysis calculated pooled odds ratio (OR) on the extracted data. Furthermore, heterogeneity, sensitivity, subgroups, and publication bias analyses were assessed. RESULTS: Twenty-six studies were included in this systematic review, with a total of 6001 cases and 135512 control people. The results of meta-analysis on 26 studies showed a significant and negative association between H. pylori colonization and CeD (pooled OR = 0.56; 95% CI = 0.45-0.70; P < 0.001), with no publication bias (P = 0.825). The L'Abbé plots also showed a trend of having more H. pylori colonization in the control group. Among subgroups, ORs were notably different only when the data were stratified by continents or risk of bias; however, subgroup analysis could not determine the source of heterogeneity. CONCLUSIONS: According to the meta-analysis, this negative association might imply a mild protective role of H. pylori against celiac disease. Although this negative association is not strong, it is statistically significant and should be further considered. Further investigations in both molecular and clinic fields with proper methodology and more detailed information are needed to discover more evidence and underlying mechanisms to clear the interactive aspects of H. pylori colonization in CeD patients. SYSTEMATIC REVIEW REGISTRATION NUMBER (PROSPERO): CRD42020167730 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=167730.

Association Between Helicobacter pylori Colonization and Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Various observational studies have examined a potential relationship between Helicobacter pylori colonization and inflammatory bowel diseases (IBDs); however, results are inconclusive. This systematic review evaluates articles reporting an association between human H. pylori colonization and IBD. METHODS: A systematic search of studies was conducted to evaluate a possible relationship between H. pylori colonization and IBD. Seven databases and different types of gray literature were searched. After screening for relevant articles, selection and data extraction were done. After that, the data were analyzed, and pooled odds ratios (ORs) were calculated, using meta-analysis. Heterogeneity, sensitivity, and subgroups analyses were conducted. Funnel plots followed by Begg and Egger tests were done to assess the publication bias. RESULTS: Among 58 studies, including 13,549 patients with IBD and 506,554 controls, the prevalence of H. pylori colonization was 22.74% and 36.30%, respectively. A significant negative association was observed between H. pylori colonization and IBD (pooled OR: 0.45, 95% confidence interval 0.39-0.53, P≤0.001). The random-effect model showed significant statistical heterogeneity in the included studies (I2=79%). No publication bias was observed. Among subgroups, ORs were notably different when the data were stratified by the age difference between patient and control group, and by study regions and/or continent. Finally, the meta-regression analysis showed significant results, in terms of the age difference and region variables. CONCLUSIONS: In this meta-analysis, all statistical data support the theory that H. pylori has a protective role in IBD. However, more primary studies using proper methodology are needed to confirm this association.

Letter to the editor: efficacy of different methods of combination regimen administrations including dexamethasone, intravenous immunoglobulin, and interferon-beta to treat critically ill COVID-19 patients: a structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: There is little information about Coronavirus Disease 2019 (COVID-19) management for critically ill patients. Most of these patients develop acute respiratory distress syndrome (ARDS) due to excessive inflammatory response and the ensuing cytokine storm. Anti-inflammatory drugs including corticosteroids can be used to effectively reduce the effect of this cytokine storm and lung damage. However, corticosteroids can have side effects, so simultaneous administration of immunoglobulin (IV-IG) and interferon-beta can help manage treatment using corticosteroids. Therefore, we designed a trial to test our hypothesis that early administration of dexamethasone in combination with IV-IG and interferon-beta can reduce the effect of the cytokine storm in critically ill patients COVID-19. TRIAL DESIGN: A phase two multi-center randomized controlled trial (RCT) with three parallel arms (1:1:1 ratio). PARTICIPANTS: They will be hospitalized patients with severe COVID-19 who have positive RT-PCR test and have blood oxygen saturation levels (SpO2) less than 90% and respiratory rate higher than 24 per minute or have involvement of more than 50% of their lung when viewed using computed tomography (CT)-scan. The age range of patients will be 18-70 years old. EXCLUSION CRITERIA: the need for intubation; allergy, intolerance, or contraindication to any study drug including dexamethasone, IV-IG, and interferon-beta; pregnancy or lactation; known HIV positive or active hepatitis B or C. The study will be conducted in several hospitals of the Golestan province, Iran. INTERVENTION AND COMPARATOR: The study subjects will be randomly allocated to three treatment arms: two experimental groups (two arms: Intervention 1 and Intervention 2) and one Control Group, which will be matched for age and sex using frequency matching method. Each eligible patient in the control arm will receive the standard treatment for COVID-19 based on WHO guidelines and the Ministry of the Health and Medical Education (MOHME) of Iran. Each patient in the Intervention Group 1 will receive the standard treatment for COVID-19 and dexamethasone, at the first 24 hours' time of admission. The intervention begins with the administration of dexamethasone based on the SpO2 levels. If the level of SpO2 does not improve after 24 hours, IV-IG (400 mg/kg once daily for 5 days) and interferon-beta (7 doses every other day) will be prescribed along with dexamethasone administration. In Intervention Group 2, the administration of dexamethasone will be started within the first 24 hours' time of admission and will be continued for 48-72 hours and then the SpO2 level will be checked. Then, if the level of SpO2 has not improved after that time, IV-IG and interferon-beta will be prescribed as the same dosage as Group 1. If the percentages of the SpO2 level are between 85 and 90/ 80 and 85/ 75 and 80/ less than 75, the dosages will be 4 mg every 12 hours/ 4 mg every 8 hours/ 8 mg every 12 hours/ 8 mg every 8 hours, respectively. According to the WHO recommendation, all participants will have the best available supportive care with full monitoring. MAIN OUTCOMES: Primary: An increase in the SpO2 level to reach more than 90% in each case, which will be assessed by the oximeter. Secondary: The duration of hospital stays; intubation status and the percentage of patients who are free of mechanical ventilation; the mortality rates during hospitalization and one month after the admission time. RANDOMISATION: Participants will be allocated into either control or intervention groups with a 1:1:1 allocation ratio using a computer random number generator to generate a table of random numbers for simple randomization. BLINDING (MASKING): The project's principal investigator (PI) is unblinded. However, the PI will not analyse the data and interpret the results. An unblinded researcher (a pharmacist) will cover the drug's bottles with aluminium foil and prepare them interventions and control drugs in a syringe with a code so that patients are blinded. This person will have no patients contact. The staff and nurses, caring for the patients, will be unblinded for each study group due to the nature of this study. The staff that take outcome measurements will be blinded. The laboratory technicians will also be blinded as well as the statistical team. These study statisticians will have access to coded data and will analyse the data labelled as group X, group Y, and group Z. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The target sample size will be 105 critically ill COVID-19 patients, who will be allocated randomly to the three trial arms with 35 patients in each group. TRIAL STATUS: Recruitment is ongoing. The study began on April 18 2020 and will be completed June 19 2020. This summary describes protocol version 1; April 2 2020. TRIAL REGISTRATION: https://www.irct.ir/. Identifier: IRCT20120225009124N4 version 1; Registration date: April 2 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The full protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.

Incidence, risk factors and clinical characteristics of extra-pulmonary tuberculosis patients: a ten-year study in the North of Iran.

OBJECTIVE: To determine the incidence of extra-pulmonary tuberculosis (EPTB) and examine the risk factors and the clinical features of the disease over a ten-year period. METHODS: Retrospective study of records of patients who were followed and registered in the TB registry programme in the health district of Gorgan, Iran from January 1, 2008, through December 31, 2017. RESULTS: Among 2280 TB records, 609 (26.71%) were EPTB. They were mostly female patients (53.7%) and residents in rural areas (56.5%) with a mean age of 40.55 years [±16]. The average age of female patients (37.55 years [±16.99]) was lower than of male patients (44.07 years [±20.59]). The median of the incidence rate was 7.5 per 100 000 inhabitants for EPTB; biopsy and pathology were the best methods for the detection of EPTB. The most frequent forms of EPTB were lymphatic TB (193/609 = 31.7%) and pleural TB (158/609 = 25.9%). In most cases (245/609 = 40.2%), one to three months elapsed between occurrence of symptoms and final confirmation of EPTB. The outcome of EPTB was weaker than of pulmonary TB (PTB). CONCLUSION: Our most important finding was the increasing incidence of EPTB, which shows the importance of attention to this disease. Lymph node and pleural tissue were the most commonly infected tissues. Skeletal TB presents a challenge in the diagnosis and treatment of EPTB.

OBJECTIF: Déterminer l'incidence de la tuberculose extra-pulmonaire (EPTB) et examiner les facteurs de risque et les caractéristiques cliniques de la maladie sur une période de dix ans. MÉTHODES: Etude rétrospective des dossiers des patients qui ont été suivis et enregistrés dans le programme d'enregistrement de la TB dans le district de santé de Gorgan, en Iran, du 1er janvier 2008 au 31 décembre 2017. RÉSULTATS: Parmi 2.280 enregistrements de TB, 609 (26,71%) étaient des EPTB. Il s'agissait principalement de femmes (53,7%) et de résidents des zones rurales (56,5%) avec un âge moyen de 40,55 ans [± 16]. L'âge moyen des patients de sexe féminin (37,55 ans [± 16,99]) était inférieur à celui des hommes (44,07 ans [± 20,59]). La médiane du taux d'incidence était de 7,5 pour 100.000 habitants pour l'EPTB; la biopsie et la pathologie étaient les meilleures méthodes pour la détection de l'EPTB. Les formes les plus fréquentes d'EPTB étaient la TB lymphatique (193/609 = 31,7%) et la TB pleurale (158/609 = 25,9%). Dans la plupart des cas (245/609 = 40,2%), un à trois mois s'étaient écoulés entre l'apparition des symptômes et la confirmation finale de l'EPTB. Le résultat de l'EPTB était plus faible que celui de la TB pulmonaire (PTB). CONCLUSION: Notre découverte la plus importante a été l'incidence croissante d'EPTB, ce qui montre l'importance de l'attention portée à cette maladie. Les ganglions lymphatiques et les tissus pleuraux étaient les tissus les plus fréquemment infectés. La TB osseuse présente un défi dans le diagnostic et le traitement de l'EPTB.

In Vitro Synergistic Effect of Vancomycin and Some Antibacterial Agents Against Clinical Methicillin-Resistant and Sensitive Staphylococcus aureus Isolates.

Methicillin-resistant Staphylococcus aureus (MRSA) can be responsible for serious long-term infections. Sometimes monotherapy can be ineffective for the treatment of these infections; hence, it is hypothesized that combined drug treatment can be more potent in these cases. The aim of this study was to investigate the synergistic effect of vancomycin and eight other antibacterial agents to identify the best combination pattern in the management of MRSA. Ameri-Ziaee double synergism test (AZDAST), double-disc, checkerboard, and time-kill methods were used to assess the synergistic effect in 24 isolates of S. aureus, including 22 MRSA and two methicillin-sensitive S. aureus (MSSA). Furthermore, based on the results, handmade combined antibiotic discs were prepared to evaluate the results of the checkerboard and time-kill methods at the plate level. All the isolates were sensitive to vancomycin, linezolid, and daptomycin. Furthermore, penicillin had the highest resistance (100%) in all isolates. The synergistic activities were observed, when the vancomycin was combined with the imipenem, using three double-disc, checkerboard, and time-kill methods. The sub-minimum inhibitory concentration (MIC) amount of the combined discs could increase the diameter of the inhibition zone, confirming the results. The data obtained from this study suggested that vancomycin and imipenem together, even at sub-MIC, could be effective against MRSA and MSSA infections.

Antimicrobial resistances, and molecular typing of Campylobacter jejuni isolates, separated from food-producing animals and diarrhea patients in Iran.

The aims of this study were to regain new epidemiology information about frequency, drug resistance rates, and typing of Campylobacter jejuni (C. jejuni) isolates, obtained from some poultry and cattle farms, slaughterhouses, and people with diarrhea. In this regard, Minimal Inhibitory Concentration (MIC) of several antibiotics and the associated antibiotic resistance genes, including tetO, tetA, cmeB, and blaOXA-61 were evaluated. The isolates were also typed, using the Fla-RFLP method. Generally, between 233 food animal samples, 80 (34.33%) C. jejuni were isolated. Moreover, 20 out of 74 (27%) human specimens suspected to infectious diarrhea were C. jejuni positive. High frequencies of resistance to tetracycline (100%), ciprofloxacin (95%), and nalidixic acid (86%), and low frequencies of resistance to florfenicol (0%), erythromycin (5%), and gentamicin (8%) were observed. Furthermore, in the tetracycline-resistant isolates, the existences of tetO, tetA, and cmeB were 86%, 23%, and 48%, respectively. There was a significant correlation between the cluster types obtained from Fla-RFLP method and antibiotic resistance pattern. The results suggested that the genomic link between Campylobacter spp. should be always evaluated in each country to provide an insight about the Campylobacter spp., spread in the region, in order to implement the health-controlling programs efficiently.

Antimicrobial Resistance and Virulence-Associated Genes of Campylobacter spp. Isolated from Raw Milk, Fish, Poultry, and Red Meat.

This study was designed and conducted to evaluate the frequency, antimicrobial resistance, and presence of six virulence-associated genes among thermophilic Campylobacters isolated from raw milk, poultry (chicken, turkey, and duck), fish, cattle, and sheep meat. Out of 590 samples, which were recovered from different origins, 141 (23.9%) samples were positive for Campylobacters. Campylobacter spp. was isolated in 40.8% (106/260), 14% (28/200), and 8.7% (7/80) of poultry meat, red meat, and milk samples, respectively. Antimicrobial susceptibility test indicated a high frequency of resistance to ciprofloxacin, tetracycline, and nalidixic acid among the isolates. Furthermore, prevalence of waaC, ciaB, and pldA genes were 91.7%, 86.7%, and 80.8%, respectively; and, none of the isolates harbored both wlaN and cgtB genes, simultaneously. Moreover, there was a weak correlation between antibiotics resistance and presence of the pathogen genes. However, the existence of Campylobacter spp. isolates in food animal products, with high resistance to antibiotics and several virulence gene possessions, is alarming and increases the attention to the widespread use of antibiotics.

The high prevalence of Mycobacterium tuberculosis Beijing strain at an early age and extra-pulmonary tuberculosis cases.

BACKGROUND AND OBJECTIVES: Tuberculosis (TB) is still responsible for a wide range of deaths worldwide. Beijing genotype is one of the most important and virulent strains in Mycobacterium tuberculosis. This study was designed for determination Beijing genotypes of M. tuberculosis in Golestan province, north of Iran. MATERIALS AND METHODS: In the current descriptive study, 238 clinical MTB isolates, obtained from patients with pulmonary and extra-pulmonary TB in north of Iran, were evaluated. Oligonucleotide primers for the Beijing and non-Beijing genotypes and specific probes for their detection by a real-time PCR method were employed. In addition, an association between the Beijing genotype and possible clinical and demographic factors was evaluated. RESULTS: The method revealed that 33 cases (13.9%) were the Beijing lineage and 205 (86.1%) the non-Beijing genotype. The mean age of patients infected with the Beijing and non-Beijing strains was 37.27 ± 18.3 and 51 ± 21.2 years, respectively; the difference was statistically significant (P = 0.001). In addition, the prevalence of the Beijing strain decreased with age. Patients with a TB infection caused by the Beijing genotype were also more vulnerable to treatment failure. Based on the origin of the samples, the Beijing genotype was more often observed in extra-pulmonary samples compared with Pulmonary ones (P = 0.001). CONCLUSION: The Beijing genotype of MTB is prevalent in our region especially among young people which could indicate the risk of further expansion in the future.

Prevalence and antibiotic resistance profile of thermophilic Campylobacter spp. of slaughtered cattle and sheep in Shiraz, Iran

Although poultry meat is considered as the main source for human Campylobacter infections, there is limited information about non-poultry sources. The present study was aimed to investigate the prevalence and the antibiotic resistance of thermophilic Campylobacter spp. in fecal samples of the cattle and sheep in Shiraz, Iran. A total of 302 fecal samples were obtained from clinically healthy, slaughtered cattle and sheep from Shiraz slaughterhouse. The animals were clinically healthy before being slaughtered. The samples were cultured according to the specific cultivation method under thermophilic conditions. The susceptibility of Campylobacter isolates were determined for 13 antimicrobial agents. All enriched samples and cultured isolates were targeted for polymerase chain reaction (PCR) detection of 16S rRNA and multiplex PCR for determining their species. Among 302 fecal samples, 65 (21.5%) and 205 (67.8%) samples were positive for the presence of Campylobacter species with the cultivation and PCR techniques, respectively. All 65 distinct isolates were susceptible to neomycin and colistin and the isolates showed high resistance to cephalotin (83.0%) and ciprofloxacin (67.7%). After the multiplex PCR, 78.5% of total positive samples showed the simultaneous presence of Campylobacter jejuni and Campylobacter coli. In conclusion, the results emphasized that non-poultry farms are important as a possible source of Campylobacter infections.