Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) - Volume 21, Issue 1, 2021

Monoclonal antibodies (mAbs) as alternatives or more often as complementary to the conventional antimicrobials have been developed for the management of infectious conditions for the past two decades. These pharmacotherapeutic strategies are inevitable as the burden of antimicrobial resistance is far-reaching in recent times. MAbs are part of the targeted pharmacotherapy armamentarium with a high degree of specificity - hence, exert comparatively superior efficacy and tolerability than the conventional polyclonal antisera. So far, only five mAbs have been approved for the management of infectious states, since the marketing authorization (1998) given to palivizumab (Synagis®) for the prophylaxis of lower respiratory tract disease caused by a respiratory syncytial virus in pediatric patients. Ibalizumab-uiyk (Trogarzo™) used for the management of multidrug-resistant HIV-1 infection not yielding to at least 10 antiretroviral drugs, was approved recently. Among the three antibacterial mAbs, raxibacumab (ABthrax®/ Anthrin®) and obiltoxaximab (Anthim®) are indicated for the treatment and prophylaxis of inhalation anthrax due to Bacillus anthracis; bezlotoxumab (Zinplava®) is used to reduce the recurrence of Clostridium difficile infection. There are also around 30 and 15 mAbs in different phases of development for viral and bacterial conditions. As alternatives to the traditional antivirals and antibacterials, the antimicrobial mAbs are the need of the hour. These mAbs are more relevant to the management of conditions like emerging viral outbreaks wherein there is a lack of prophylactic vaccines. The current cutting-edge engineering technologies revolutionizing the production of mAbs include phagedisplayed antibody libraries, cloning from single-memory B cells or single-antibody-secreting plasma B cells, proteomics-directed cloning of mAbs from serum clubbed with high-throughput sequencing techniques. Yet, the cost of manufacture continues to be the main limiting factor. In this review, the different therapeutic monoclonal antibodies directed against the microbial pathogens are discussed.

Background: Nowadays, due to the incidence of specific strains of Mycobacterium tuberculosis and also an increase in the rate of drug resistant-TB, the mortality rate has been increased by this disease. The identification of common strains in the region, as well as the sources of transmission, is essential to control the disease, which is possible by using molecular epidemiology. Objectives: In this survey, the studies utilizing the spoligotyping method in Muslim Middle East countries are reviewed to determine their role in the control of TB. Methods: All studies conducted from 2005 to June 2016 were considered systematically in three electronic databases out of which 23 studies were finally selected. Results: The average rate of clustering was 84% and the rate of recent transmission varied from 21.7% to 92.4%. The incidence of Beijing strains has been found to be rising in the abovementioned countries. In Iran and Saudi Arabia known as immigration and labour-hosting countries, respectively, rapid transmittable and drug-resistant Beijing strains were higher than those in other Muslim Middle East countries. Conclusion: Considering the incidence of highly virulent strains, due to the increase in immigration and people infected with HIV, tuberculosis, especially drug-resistant form, careful monitoring is needed.

Background: Toxin-antitoxin systems (TAs) are two-component elements, which are extensive in the bacterial genome and have a regulatory role in many cellular activities including, growth arrest, survival, biofilm formation, and bacterial persistence. Objective: TAs have not well studied in Brucella spp. Methods: We evaluated the presence of different toxin-antitoxin systems, including relE- rhhlike, Fic- Phd, Cog- Rhh, and cogT- cogAT in 40 clinical Brucella melitensis isolates using PCRbased sequencing assay. Results: Our results showed the high presence of relE-rhh-like, Fic-Phd, Cog-rhh, and cogTcogAT s TAs genes in B. melitensis isolates that were 96.25%, 92.5%, 96.25%, and 95%, respectively. Conclusion: A high presence of TAs genes in clinical B. melitensis isolates revealed that the TA system could be an antibacterial target in B. melitensis but more investigation is necessitated to elucidate the exact roles of these genes.

Introduction: Parasitic myositis is caused by some parasites, such as Toxoplasma gondii) T. gondii (and Toxocara canis (T. canis). So, the aim of the study was to evaluate the prevalence T. gondii and T. canis in patients with myositis and healthy individuals. Methods: A total of 108 samples were randomly selected as the control (54 healthy individuals) and test (54 myositis patients) groups. IgG and IgM antibodies (Ab) against T. gondii and IgG Ab against T. canis were measured by the enzyme-linked immunosorbent assay (ELISA). The detection of chronic and acute toxoplasmosis was performed by the ELISA IgG avidity. The presence of T. gondii in the blood was evaluated using the nested polymerase chain reaction (nested-PCR). Results: Of 108, 33 (30.6%) cases were positive for IgG against T. gondii that 19 (35.2%) and 14 (25.9%) were observed in myositis patients and healthy individuals, respectively (P=0.296). Of 19 positive cases, 12 (63.2%) and 7 (36.8%) cases were detected as chronic and acute toxoplasmosis, respectively, while, all positive cases in the control group had chronic toxoplasmosis (P=0.013). One (1.9%) sample was positive for anti- T. gondii IgM and two (3.7%) samples were positive for IgG against T. canis by the ELISA that these positive cases were observed only in myositis patients (P=1.000 P=0.495, respectively). B1 T. gondii gene was amplified in 12 (63.2%) and 1 (7.1%) in myositis patients and healthy subjects (P=0.001). Conclusion: Our findings showed that there was a relatively high prevalence of acute toxoplasmosis in myositis patients in comparison with the control subjects in the Southwest of Iran.

Background: Leishmaniasis is one of the major diseases caused by the intracellular parasite of Leishmania. It has become one of the most dangerous health problems today. Our aim of the present study is to compare the effects of Sambucus ebulus leaf and fruit extracts on Leishmania major in vitro. Methods: In this study, we used MTT, promastigote and amastigote assay to evaluate the effect of different concentrations of the extract on parasite and we compared their effects. The flow cytometry technique was also used to detect the apoptotic effect of the extracts on promastigotes. Results: According to MTT experiment IC50 concentration of leaf and fruit extracts on parasite was 157 μg/ml and 265 μg/ml, respectively. After analysis by flow cytometry, leaf and fruit extracts also showed the apoptosis effect. Leaf and fruit extract caused 40.2 and 2.67 percent apoptosis. Conclusion: Based on the above assessment, we determined that the S. ebulus leaf extract has a more toxic effect on promastigotes and amstigotes than its fruit extract and maybe in the future that be used as a drug candidate.

Background: Cotrimoxazole is the main antibiotic used in HIV-infected patients for the prophylaxis of opportunistic infections. This antibiotic is prescribed in patients receiving antiretroviral agents (ART) such as Atazanavir (ATV), a protease inhibitor used with other ART classes. The objective of this study was to compare HIV treatment failure (HIVTF) in HIV-infected patients treated concomitantly with ATV and cotrimoxazole to those of patients treated only with ATV. Materials and Methods: This is a comparative analysis of the safety data of HIVTF available with ATV in the WHO International Pharmacovigilance database "VigiBase®". We used the SMQ (Standardized MedDRA Querie) to identify all the terms corresponding to HIVTF. We presented results as a percentage or an adjusted Reporting Odds Ratio (aROR) with a 95% confidence interval (95% CI). Results: A total of 116 cases of HIVTF (2.2%) were reported with ATV among the 5196 individual case safety reports (ICSR) included in the analysis. The proportion of HIV-infected patients who presented ATV treatment failure (ATVTF) was lower (2.6%, 3/116) when cotrimoxazole was concomitant (aROR was 0.5 with a 95%CI from 0.2 to 1.7). Only 10 of 273 ICSRs (3.7%) were reported from Africa concerning the use of cotrimoxazole prophylaxis concomitantly with ATV. Conclusion: This study did not show a higher occurrence of ATVTF when cotrimoxazole was concomitant. These results reinforce the place of concomitant use of ATV with cotrimoxazole in the management of HIV treatment.

Background: It is made clear that salt and pepper retinal lesion (SPRL) has subsequently associated with the infection with Giardia lamblia (G. lamblia). However, little is known regarding the prevalence of SPRL among patients suffered from parasitic infections in the world. Objective: This study aimed to determine the prevalence of SPRL among patients with intestinal protozoan infections, for the first time, in Sari, northern Iran. Methods: In this case-control study, a total of 150 subjects participated: 75 were in the patients group diagnosed to have an intestinal parasite and 75 in the control group without any intestinal infection. Fecal samples were obtained from all participants and examined with wet mount and formalin-ether methods. The retina of both groups was examined by an ophthalmologist. Results: Overall, salt and pepper retinal changes were diagnosed in 12 (16 %) patients with at least one parasitic infection (7 females and 5 males). G. lamblia was diagnosed in 6 subjects (50%), Blastocystis hominis in 5 (41.6%), and Entamoeba coli in 1 (8.3 %). Most of the patients (58.3%) had a mild infection. Bilateral retinal involvement was observed in 75% of the patients. Furthermore, macula involvement was observed in 91.7 % with SPRL. Conclusion: Our findings indicated the relatively high prevalence of SPRL in subjects with giardiasis and blastocystosis. It can be concluded that not only G. lamblia but also B. hominis can cause SPRL in Sari, Iran. Further studies are needed to find other etiologic parasites able to cause retinal damages.

Introduction: Nasal carriers of Staphylococcus aureus are common and play an important role in the transmission of infections. The aim of this study is a phenotypic and molecular investigation of nasal methicillin- and vancomycin-resistant S. aureus in hospitalized patients. Methods: 202 nasal swabs were collected from patients at Prince Hamzah Hospital, Jordan, through 2016-2017. Swabs were processed according to standard microbiological procedures to isolate Staphylococci. Antibiotic susceptibility testing was performed using disk diffusion, E-test, microdilution and Vitek 2. Methicillin resistance was confirmed by testing for the mecA gene, while vancomycin resistance was screened by testing for the vanA and vanB genes. Results: The mean age of participants was 50.17±18.18 years and 59.4% were females. Nasal Staphylococci was isolated in 64/202 (31.7%), S. aureus was isolated from 33 samples (16.3%), MRSA was isolated from 13 samples (6.4%) and constitutive Macrolide-lincosamidestreptogramin B (MLSB) was isolated from 12 samples (5.9%). All MRSA isolates harbored the mecA gene. All isolates were sensitive to vancomycin using E-test and the microdilution test and were negative for the vanA and vanB genes. The highest resistance rate was observed for benzylpenicillin (>90%), while the lowest resistance rate was for tobramycin (<5%) among all isolates. Nasal Staphylococci, S. aureus and MRSA colonization significantly correlate with increased number of family members and previous hospitalization (P<0.05), while nasal S. aureus significantly correlates with a history of skin infection (P=0.003). Conclusion: Nasal colonization by mecA-mediated MRSA is common among hospitalized patients, while vanA- and vanB-mediated vancomycin resistance was not detected in any nasal isolates.

Objective: Nocardiosis is an opportunistic infection in individuals who had organ transplants and in patients with immunosuppressive diseases such as pemphigus Vulgaris (PV), diabetes mellitus, and HIV. Nocardiosis rate has not been assessed in Iranian PV patients, and this was the first study to estimate nocardiosis rate in these patients. Methods: In this study, 103 patients with PV were examined. BAL samples were obtained and direct smear was prepared and visualized by microscopy after PAS staining. Samples were cultured on antibiotic-containing blood and chocolate agar media. DNA extraction and PCR were performed on positive cultures, and final identification was done by 16S rRNA gene sequencing. Drug susceptibility testing was done by microbroth dilution method. Results: Four positive cultures (3.88%) were found in the samples (n = 103). According to sequence analysis, 2 isolates were identified as Nocardia cyriacigeorgica and 2 as Nocardia otitidiscaviarum and Nocardia cerradoensis. Nocardia cerradoensis was isolated from an invasive brain infection. Isolated bacteria were susceptible to majority of the tested antibiotics, except for 2 strains of Nocardia cyriacigeorgica and Nocardia cerradoensis. This was the first isolation of Nocardia cerradoensis of human infection in Asia. Patients with PV are susceptible to nocardiosis, similar to other immunocompromised patients. Conclusion: Pemphigus Vulgaris is a severe autoimmune disease which is treated by a high dosage of corticosteroids. Opportunistic infections are one of the greatest challenges of these patients. One of the neglected agents of opportunistic infection in this disorder is Nocardiosis which can cause a high mortality rate in PV patients.

Introduction: The members of the tribe Proteeae, Morganella and Providencia are being increasingly recognized as important pathogens. The spectrum of disease caused by them is wide and in reported cases, the mortality is high. Previously both of these pathogens were considered to be rare pathogens as the potential to cause nosocomial transmission and infection was not much studied. But their phenomenal evolution and increase in multidrug-resistance (MDR) strains of these pathogens are posing a major threat toward public health throughout the world. Methods: This present study was carried out from July 2018 to December 2018 on all the pus and body fluid samples that were received in the Department of Microbiology. Samples were processed as per the standard Microbiological guidelines and also were analyzed for their antimicrobial susceptibility profile as per Clinical Laboratory Standards Institute. Results: Out of 8425 samples received, 2140 were culture positive, amongst which 19 samples (0.89%) were positive for Providencia species (9) and Morganella morganii(10). The male : female ratio of these 19 patients was 2.8 : 1 and maximum patients (13) belonged to 20-60 years. As far as risk factors are concerned, maximum patients were diabetics (7) followed by abnormal liver function tests (6), concomitant UTI (6), history of invasive procedure (5), prior exposure to antibiotics (5) and urinary catheterization (4). About 6 were polymicrobial infections. Antibiotic susceptibility patterns revealed that Providencia strains were sensitive to ampicillin- sulbactum (77.7%) and amikacin (77.7%), while all Morganella strains were 100% sensitive to tobramycin and piperacillintazobactam. Conclusion: This study heralds in need for more research in this area as infections caused by these two pathogens are on the rise. Moreover, resistance to antimicrobials is also an increasingly common problem thus delaying the treatment and prognosis of the disease.

Background: Multidrug Resistant Pseudomonas aeruginosa (MDRPA) is a ubiquitous opportunistic organism that poses threat to the management of infections globally. Objectives: The objectives of the current research were to assess the antibiotic resistance profiles as well as Multiple Antibiotic Resistance (MAR) Index of clinical isolates of P. aeruginosa associated with wound infections. Presence of Extended Spectrum Beta Lactamase genes (bla CTX-M, bla SHV and bla TEM) and Carbapenemase genes (bla KPC and blaNDM) were also determined among the isolates. Methods: Swab samples were collected from 255 patients with wound infections. Bacterial identification was done by standard diagnostic tests. The identity of isolates was confirmed by the detection of the exoA gene using the PCR technique. Antibiotic susceptibility testing and resistance profile were determined using the disc diffusion method. Resistance genes were amplified by the PCR method. Results: A total of 235 (92.2%) bacterial isolates were recovered from the wounds of the 255 patients, of these, 124 (52.8%) were Gram-negative bacilli while the remaining 111 (47.2%) were Gram-positive cocci. A total of 69 Pseudomonas aeruginosa strains were recovered from the wound specimens. Imipenem was the most effective antibiotic against these isolates (92.8% isolates were susceptible) while all isolates were resistant to Meropenem, Cefepime, Ticarcillin, Amoxicillin-clavulanic acid, Cefotaxime, Ampicillin and Cefpodoxime. All 69 Pseudomonas aeruginosa isolates were multidrug resistant (MDR). Of the isolates selected for PCR, all were positive for TEM, CTX-M and SHV genes while one-third were blaKPC and blaNDM producers. Conclusion: This study demonstrated high prevalence of carbapenem-resistant strains of P. aeruginosa, suggesting that there is an urgent need in Nigeria for the enactment and enforcement of policies and necessary laws restricting the availability and indiscriminate use of antibiotics.

Introduction: A waterborne outbreak of hepatitis E virus occurred in the Jamshedpur city of Jharkhand from March 2018 to October 2018. The aim of the present study is to study the hepatitis E virus outbreak clinically, serologically and etiologically. Methods: Five hundred and eighty-four clinically and biochemically documented cases were screened for the hepatotropic viral markers (HepatitisA, B, C, and E) by the ELISA. Demographic data such as gender, age, clinical diagnosis, location, outcome and time of admission were extracted from the online hospital management system. Water samples from the affected area were tested for HEV RNA detection. Genotyping of HEV virus was carried out by sequencing and phylogenetic analysis. Results: Hepatitis E genotype 1 was confirmed as the major etiological agent in this outbreak due to the faecal contamination of drinking water supply while establishing illegal water connections. Mixed infection of HEV-HAV (5.31%) or HEV-HBV (0.91%) was also detected in the present series of acute viral hepatitis. Conclusion: The study highlights the importance of screening for both enterically transmitted hepatotropic viral markers as well as the parenterally transmitted hepatotropic viral markers during the outbreaks of acute viral hepatitis.

Purpose: Acinetobacter baumannii is an opportunistic pathogen, and is among the most problematic nosocomial infections as well as community-acquired infections. This retrospective study was conducted as an attempt to determine the prevalence of multidrug-resistant A. baumannii (MDRAB) isolates from the north and central Jordan area during 2018. Methods: Patients’ records provided by an accredited central private laboratory located in Amman, were examined for A. baumannii isolates identified during this period. The isolates were identified to the species level using the API-10S system and the antimicrobial sensitivity testing was determined using the Kirby–Bauer disc diffusion method. Results: A total of 43 unduplicated isolates were obtained and classified according to clinical sampling source into: Group I (blood), Group II (urine) and Group III (wound, pus, sputum, bedsore and others). Total MDRAB isolates recorded were 29 (67.4 %). Resistance to imipenem was found to be 36% and 94% among groups II and III, respectively, and resistance to meropenem was 60% and 88% among the same groups, respectively. Conclusion: Antimicrobial stewardship programs at a national scale are needed to calculate the actual proportion of MDRAB in the country and to combat its increasing emergence and decrease the magnitude of antibiotic resistance.

Background: Cervical cancer is the most common cancer in women. High-Risk HPV types are known as the main agents involved in genital and cervical malignancies. There may be co pathogens like STIs that are involved in enhancing the susceptibility and progression to cervical neoplasia. This study was conducted to detect C. trachomatis, HSV-2 and M. genitalium using qPCR in women suffering from cervical intraepithelial neoplasia, HPV infection and non cancerous- non HPV subjects for the association of burden of genital disorders. Materials and Methods: This descriptive study was performed on 195 Liquid Based Cytology (LBCs) specimens collected from women referred to private laboratories. Fifty, 98 and 47 samples were from women with known CIN, HPV positive and non-cancerous/non-HPV, respectively. HSV-2, C. trachomatis, M. genitalium and HPV genotypes have been detected using multiplex TaqMan Real Time PCR and PCR hybridization. Results: A total of 148 HPV positive samples were included. HPVs 6 (35.13%), 16 (32.43%), 18 (21.62%), 11 (9.46%), 31 (9.46%), and 51 (9.46%) were the most common genotypes. Single, 2, 3, and more than 4 multiple HPV genotypes were detected in 46%, 29.7%, 14.2%, 10.1% cases, respectively. The prevalence of M. genitalium, C. trachomatis and HSV2 was 3 (1.54%), 24 (12.3%) and 1(0.5%), respectively. There were no statistically significant differences between these pathogens and cervical intraepithelial neoplasia (p≥ 0.05). Conclusion: HR-HPV genotypes were more prevalent in genital infections and cervical cancer. It would seem early detection of dominant STI pathogens such as Chlamydia spp. gains due to effective prevention. Here, further research is needed to understand the co-infections burden of HPV genotypes with STIs in clinical manifestations.

Background: Multidrug resistance among ESBL producing isolates has limited the administration of proper antibiotics. It is, therefore, important to monitor the resistance patterns of Klebsiella pneumoniae isolates and provide infection control strategies to prevent nosocomial outbreaks. This study was aimed to determine antimicrobial resistance patterns of K. pneumoniae isolates obtained from wound infections of patients in Tehran, Iran. Methods: A total of 102 K. pneumoniae isolates were obtained from wound infections of patients in Tehran, Iran. The production of phenotypic ESBL and carbapenemase was assessed using the double-disc synergy test (DDST) and modified Hodge test (MHT), respectively. PCR was performed for the detection of ESBL, carbapenemase, quinolone and aminoglycoside resistance genes. Results: Forty-six (45.1%) and 23 (22.5%) isolates, out of the 102 isolates, were phenotypically detected as ESBL and carbapenemase producers, respectively. The PCR results showed that 80/102 (78.4%) and 51/102 (50%) isolates possessed at least one of the assessed ESBL and carbapenemase genes, respectively. Quinolone resistance determinants (QRDs) and aac(6')-Ib genes were found amongst 50 (49%) and 67 (65.7%) isolates, respectively. Four isolates carried blaTEM, blaSHV, blaCTX-M, qnrB, qnrS and aac(6’)-Ib genes, simultaneously. Conclusion: Due to the presence of multiple resistance genes among some K. pneumoniae strains, antibiotic agents should be used with caution to preserve their efficacy in case of life-threatening infections.

Introduction: Echinococcosis, as an important zoonotic infection, has a major worldwide distribution. Pediatric echinococcosis has still become health concerning issue in developing countries, particularly, in the Middle East and Iran. The aim of this study was to investigate the human echinococcosis in children in northern Iran. Methods: Patients admitted to the pediatric subspecialty hospital of Amir Kala, Babol, Iran, from 2011 to 2016 with a confirmed diagnosis of echinococcosis, were reviewed. Records of the patients, including demographic data, clinical manifestations of the disease, type of cysts, and other related factors, were collected. Results: Sixteen pediatric patients, twelve (75%) male, and four (25%) female were evaluated. All cases had cystic echinococcosis. The results showed that fever (75%) following vomiting, nausea, and coughing (44%) were the most common clinical manifestations. The most common localizations of cases were determined as liver (n=10, 62.5%) and lung (n=9, 56%). The frequency of the involvement of more than one organ was 31% (5 cases). The co-occurrence of liver and lung was seen in 2 (12.5%) cases, and in one case, the co-occurrence of the liver and spleen was reported. In one case, lung, liver and, the pelvis was involved, while in another case, liver, sub diaphragm and kidney involvement were observed. Conclusion: Cystic echinococcosis should be kept in mind when a cystic lesion is encountered anywhere in the body, particularly, in patients lining in the endemic regions. Since cystic echinococcosis has a considerable economic impact in Iran, the implementation of a control program and the surveillance system are highly recommended to reduce the economic burden of this disease.

Background: Chronic urticaria (CU) has a range of clinical demonstrations and causes. Parasitic infections are mentioned as one of the main causes of the CU. Objectives: The aim of this study was to investigate the prevalence of intestinal parasites in patients with CU (with duration time of more than 6 weeks) compared healthy subjects. Methods: A total of 169 cases and 210 controls were included in this study. Ages ranged from 1 to 77 years old. Three samples were gathered from each patients and direct wet mount, formol-ether concentration, Ziehl-Neelsen and trichrome staining were used. Results: Out of the 379 individuals examined here, 208 were from urban areas and 171 from rural areas. Three stool samples were taken from each patient in three consecutive days. Based on parasitological tests, 7 (4.1%) cases from 169 patients with CU and 6 (2.9%) cases from 210 non- CU group individuals were positive for intestinal parasites. Conclusion: The prevalence of various parasites between case and control groups was not significant.

A molecular method for diagnosis of drug-resistant Tuberculosis is Multiplex allele-specific PCR (MAS-PCR), which is more time-efficient, and its accuracy is studied using DNA sequencing. Also, understanding the role of mutations, when translated to protein, in causing resistance helps in better drug designing. Aim: To study MAS-PCR in the detection of drug resistance in comparison to DNA sequencing in Mycobacterium tuberculosis, and understand the mechanism of interaction of drugs with mutant proteins. Methods: MAS-PCR was used for the detection of drug-resistant mutations and validation was done through DNA sequencing. MAS-PCR targeted four genes, iniA for the drug Ethambutol, rpsL and rrs for Streptomycin, and gyrA for Fluoroquinolone resistance, respectively. Further, the sequence data was analysed and modeled for in silico docking to study the effect on the interaction of the anti-TB drug molecule with the target protein. Results: We identified drug-resistant mutations in four out of 95 isolates with one of them carrying a mutation at codon iniA501, two at gyrA94, and one for both iniA501 and gyrA94 using MASPCR. DNA sequencing confirmed drug-resistant mutations in only two isolates, whereas two others had mutation adjacent to the target allele. Drug-protein docking showed Estimated Free Energy of Binding to be higher for Fluoroquinolone binding with GyrA D94V mutant. Both wild and mutant IniA interact with EMB but had no significant effect on binding energy. Conclusion: DNA sequencing-based drug resistance detection of TB is more accurate than MASPCR. Understanding the role of mutations in influencing the drug-protein interaction will help in designing effective drug alternatives.

Introduction: Epididymo-orchitis is a common urological disease among men. Little is known about the clinical and epidemiological aspects of the disease in Iran. Thus, the present study was aimed at investigating the etiology, clinical sequelae and risk factors of patients with epididymo- orchitis in Tehran, Iran. Methods: Patients presenting with epididymo-orchitis were prospectively analyzed in order to study the etiology and pattern of the disease. Bacteriological, molecular and serological tests were undertaken to look for Chlamydia trachomatis, Neisseria gonorrhoeae, Brucella spp., Mycoplasma spp, and other bacteria. Results: Fifty patients with epididymo-orchitis were evaluated according to their clinical symptoms, duration of symptoms, physical examination, and laboratory studies. The mean age of the patients was 53 years. Fever, dysuria, pain in the flanks, urinary frequency and discharges occurred in 58.0%, 50.0%, 50.0%, 28.0% and 6.0%, respectively. Bacterial pathogen was identified in 26% (13/50) of patients by urine culture. Escherichia coli was the etiological agent in 11/13 patients (84.6%). Two out of 50 patients (4.0%) were also positive for Chlamydia trachomatis. Two samples were serologically positive for Brucella spp. High Mean age, fever, urinary frequency, history of the underlying disease and history of urinary tract infections were found to have a significant association with the positive bacteriologic urine culture (P<0.05). Conclusions: The most common clinical manifestations were fever, dysuria, and abdominal pain. E. coli and C. trachomatis were the major causative agents. The use of a set of diagnostic approaches including clinical symptoms, urine culture and more precise techniques such as PCR should be taken into consideration for the definitive diagnosis.

Purpose: Urinary tract infection (UTI) is one of the serious infections caused by the bacteria Enterococci. Vancomycin-Resistant Enterococci (VRE) is a persevering clinical problem globally. This study aims to detect high-level aminoglycoside and vancomycin resistance in uropathogenic Enterococcus spp. Methodology: A total of 75 clinically relevant Enterococcus spp. grown from urine samples, were collected following convenience non-random sampling method. Identified by standard biochemical tests and susceptibility to antibiotics was studied by Kirby Bauer’s disc diffusion method. The MIC of vancomycin was detected by agar dilution test. Van A, and Van B genes in VREs were detected by PCR. Results: Among 75 Enterococcal isolates, 43 (57.3%) were E. faecalis, 12 (16%) were E. faecium, 6 (8%) of each were E. pseudoavium and E. casseliflavus, 5(6.66%) were E. dispar and 3 (4%) were E. durans. E. faecalis (n=19) and E. faecium (n=3) were resistant to High Level Streptomycin (HLS). E. faecalis (n=21) and E. faecium (n=6) were resistant to High Level Gentamicin (HLG). 4 (9.3%) E. faecalis were vancomycin-resistant, out of which 3 were of Van A, and one was both Van A and Van B genotype. Conclusion: Isolation of high level aminoglycoside resistant (HLAR) Enterococci is a challenge for the treating physician because aminoglycoside cannot be used in combination with glycopeptide or ampicillin for such isolates. The occurrence of HLAR, Van A, and Van B VRE genotypes is a cause of concern as they may transfer drug resistance genes to other bacterial isolates, thus leading to limited therapeutic options.

Background: Toxoplasmosis is a disease that results from infection with an obligate intracellular T. gondii parasite, one of the world's most common parasites. Considering the complications of chemical drugs and the need for an appropriate drug combination for treatment of toxoplasmosis and considering the antimicrobial potential of chitosan, as a natural source, this study was aimed to evaluate in vitro activity of commercial chitosan (CC) on T. gondii. Methods: In this experimental study, the tachyzoites of T. gondii were collected from the peritoneal exudates from infected Balb/c mice. The tachyzoites were diluted in phosphate buffer saline (PBS) solution. Chitosan with low molecular weight was commercially purchased. Then, at concentrations of 10, 50, 100, and 200 μg/mL and after 30, 60, 120, and 180 minutes, the viability of tachyzoites was determined by using trypan blue 0.1%. Anti-T.gondii activity of CC in all concentrations was significantly higher than pyrimethamine as the control group (P=0.05). Results: The concentration of 200 μg/mL of CC had the highest effects and killed 30.5, 52, 59, and 81.5% of tachyzoites after 30, 60, 120, and 180 minutes. Moreover, IC50 values of CC were 515, 171, 12.5, and <10 μg/mL in comparison with pyrimethamine as 58.82 μg/mL for 30, 60, 120, and 180 min of exposure time. Conclusion: Our results indicate that chitosan in low molecular weight had potent activity against T. gondii tachyzoites and could be an appropriate candidate for the treatment of at least acute toxoplasmosis, certainly, after complementary in vivo experiments.

Background: Dengue fever is an arthropod-borne viral infection with a very high incidence rate in Southeast Asia. Most patients present with self-limiting febrile illness, while some patients may develop complications like acute kidney injury, acute liver failure, myocarditis or Guillain– Barre syndrome. The coexistence of Dengue and MRSA (Methicillin-resistant Staphylococcus aureus ) is rarely reported in the literature. Case: A 28-year-old male is presented with high-grade fever, polyserositis and thrombocytopenia. The patient was treated symptomatically for dengue infection. During the course of hospitalization, patient developed neck swelling (thyroid abscess) and left forearm abscess. MRSA was isolated from blood culture and pus, and successfully treated with iv antibiotics (Vancomycin). Conclusion: High anticipation and vigilance are required to detect concurrent bacteremia in dengue patients. Early recognition of warning signs with readily antibiotic therapy is important to prevent mortality and morbidity in these patients. Our report also highlights the MRSA as a rare cause of thyroid abscess, with only 5 cases reported in the literature so far.