Targeted delivery of therapeutic molecules into cancer cells is considered as a promising strategy to tackle cancer. Antibody-drug conjugates (ADCs), in which a monoclonal antibody (mAb) is conjugated to biologically active drugs through chemical linkers, have emerged as a promising class of anticancer treatment agents, being one of the fastest growing fields in cancer therapy. The failure of early ADCs led researchers to explore strategies to develop more effective and improved ADCs with lower levels of unconjugated mAbs and more-stable linkers between the drug and the antibody, which show improved pharmacokinetic properties, therapeutic indexes, and safety profiles. Such improvements resulted in the US Food and Drug Administration approvals of brentuximab vedotin, trastuzumab emtansine, and, more recently, inotuzumab ozogamicin. In addition, recent clinical outcomes have sparked additional interest, which leads to the dramatically increased number of ADCs in clinical development. The present review explores ADCs, their main characteristics, and new research developments, as well as discusses strategies for the selection of the most appropriate target antigens, mAbs, cytotoxic drugs, linkers, and conjugation chemistries.

Introduction: Limited specific data and investigations are available for invasive aspergillosis (IA) in pediatric patients. We evaluated the diagnostic potential of three noninvasive tests including the Platelia Aspergillus EIA kit for using galactomannan antigen, (1,3)-β-D-glucan Detection Reagent Kit, and nested-PCR for Aspergillus DNA in sera. We evaluated the diagnostic potential of three noninvasive tests including EIA for galactomannan antigen (Platelia Aspergillus), nested PCR assay for Aspergillus DNA and test for (1→3)-β-D-glucan (Glucatell assay Kit). Methodology: All pediatric patients treated at the hematology/oncology unit who were at increased risk of developing invasive aspergillosis were enrolled. Clinical samples were examined for Aspergillus infections by mycological methods. Serial blood samples were collected twice weekly and evaluated by noninvasive tests. Results: We analyzed 230 consecutive blood samples from 62 pediatric patients. The incidence rate of invasive aspergillosis in the patients was found to be 27.4%, and the etiologic agents were Aspergillus flavus, Aspergillus fumigatus, and Aspergillus spp. The sensitivity, specificity, positive and negative predictive values, and likelihood ratios for positive and negative results of galactomannan in patients with proven and probable IA were 90%, 92%, 81.8%, 96%, 11.25, and 0.1; for beta-D-glucan they were 50%, 46%, 26%, 70.6%, 0.9, 0.9; and for nested-PCR they were 80%, 96.2%, 88.9%, 92.6%, 21, and 0.2, respectively. Conclusions: The conventional methods are not able to detect IA, due to the lack of valid and proper sampling. Galactomannan and nested-PCR tests in serum, with enough accuracy and reliability, can serve as noninvasive methods for the detection of IA in pediatric patients. However, the beta-D-glucan test cannot serve as an efficient diagnostic tool in those with hematologic disorders.

Background. Diabetic foot infections (DFIs) are a major public health issue and identification of the microorganisms causing such polymicrobial infections is useful to find out appropriate antibiotic therapy. Meanwhile, many reports have shown antibiotic resistance rising dramatically. In the present study, we sought to determine the prevalence of microorganisms detected on culture in complicated DFIs in hospitalized patients and their antibiotic sensitivity profiles. Methods. A cross-sectional study was conducted for a period of 24 months from 2012 to 2014 in Nemazee Hospital, Shiraz, Iran. The demographic and clinical features of the patients were obtained. Antimicrobial susceptibility testing to different agents was carried out using the disc diffusion method. Results. During this period, 122 aerobic microorganisms were isolated from DFIs. Among Gram-positive and Gram-negative bacteria, Staphylococcus spp. and E. coli were the most frequent organisms isolated, respectively. Of the isolates, 91% were multidrug while 78% of S. aureus isolates were methicillin resistant. 53% of Gram-negative bacteria were positive for extended-spectrum β-lactamase. Conclusion. Given the involvement of different microorganisms and emergence of multidrug resistant strains, clinicians are advised to consider culture before initiation of empirical therapy.

Background:Tatumella ptyseos is a rod-shaped, Gram-negative, facultative, and anaerobic bacteria categorized in the Enterobacteriaceae family. It is a rare food-borne opportunistic pathogen which causes neonatal sepsis, bacteremia, and urinary tract infections. T. ptyseos has been also cultured from various food sources around the world.Objectives:It is difficult to determine the source of the infection in the patients (especially newborns) due to low information about the epidemiology of T. ptyseos. The current study aimed to investigate the isolation, identification and antimicrobial susceptibility pattern of T. ptyseos strains from the consumed powdered infant formula milk (PIF) in hospital neonatal intensive care unit (NICU).Materials and Methods:A total of 125 powdered infant formula milk (PIF) samples were purchased from drug stores from June 2011 to March 2012. T. ptyseos was isolated according to food and drug administration (FDA) method. For final confirmation, biochemical testes embedded in API-20E system were used. Drug susceptibility test was performed using the disc diffusion method, according to clinical and laboratory standard institute (CLSI) recommendations.Results:Results of the study showed that, out of 125 samples, T. ptyseos was isolated from four (3/2%) PIF samples. All isolated strains (100%) were resistant to ampicillin, carbenicillin, cotrimoxazole and amoxicillin.Conclusions:The present study was the first report on the isolation and identification of T. ptyseos from PIF in Iran. T. ptyseos are frequently present in various kinds of foods; therefore, further investigation on these samples is required. It is necessary to track the T. ptyseos in a wide variety of foods and individuals especially in immunocompromised people such as human immunodeficiency virus (HIV)-positive patients to reveal the possible routes of transmission of this pathogen to humans. In addition, molecular studies are required to determine the genetic relationship between T. ptyseos strains isolated from different sources.

Stenotrophomonas maltophilia is an environmental Gram-negative bacterium that has rapidly emerged as an important nosocomial pathogen in hospitalized patients. Treatment of S. maltophilia infections is difficult due to increasing resistance to multiple antibacterial agents. The purpose of this study was to determine the phenotypic and genotypic characterization of S. maltophilia isolates recovered from patients referred to several hospitals. A total of 164 clinical isolates of S. maltophilia were collected from hospitals in various regions in Iran between 2016 and 2017. Antibiotic susceptibility testing was performed by disc diffusion method and E-test assay according to the Clinical and Laboratory Standards Institute (CLSI) guideline. The ability of biofilm formation was assessed with crystal violet staining and then, biofilm-associated genes were investigated by PCR-sequencing method. The presence of L1 (a metallo-β-lactamase), L2 (a clavulanic acid-sensitive cephalosporinase), sul1 and sul2 (resistance to Trimethoprim/Sulfamethoxazole), Sm qnr (intrinsic resistance to quinolones), and dfrA genes (dihydrofolate reductase enzyme that contributes to trimethoprim resistance) was also examined by PCR-sequencing. Relative gene expression of smeDEF efflux pump was assessed by real-time PCR. Genotyping was performed using the multi-locus sequencing typing (MLST) and repetitive extragenic palindromic-PCR (Rep-PCR). Isolates were resistant to imipenem (100%), meropenem (96%), doripenem (96%), and ceftazidime (36.58%). Notably, 5 (3.04%) isolates showed resistant to trimethoprim-sulfamethoxazole (TMP-SMX), an alarming trend of decreased susceptibility to TMP-SMX in Iran. Minocycline and levofloxacin exhibited the highest susceptibility of 91.46 and 99.39%, respectively. Using the crystal violet staining, 157 (95.73%) isolates had biofilm phenotype: 49 (29.87%), 63 (38.41%), and 45 (27.43%) isolates were categorized as strong-, moderate- and weak-biofilm producer while 7 isolates (4.26%) were identified a non-biofilm producer. Biofilm genes had an overall prevalence of 145 (88.41%), 137 (83.53%), and 164 (100%) of rmlA , rpfF , and spgM , respectively. L1 , L2 , Smqnr , sul1 , and sul2 resistance genes were detected in 145 (88.41%), 156 (96.12%), 103 (62.80%), 89 (54.26%), and 92 (56.09%) isolates, respectively. None of the S. maltophilia isolates were positive for dfrA12 , dfrA17 , and dfrA27 genes. Gene expression analysis showed that smeD efflux system was overexpressed in two out ...

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The aim of this study was to characterize virulence determinants and antibiotic resistance profiles in enterococci obtained from various clinical sources in the northwest of Iran. A total of 160 enterococcal clinical isolates from various wards of University Teaching Hospitals were collected and specified by biochemical test, from September 2014 to July 2015. Identification of enterococci was confirmed by multiplex PCR in the genus and species level. Antibiotic resistance properties and virulence determinants were examined by phenotypic and molecular methods. Of 160 enterococcal isolates, 125 (78.12%) and 35 (21.88%) isolates were identified as Enterococcus faecalis and Enterococcus faecium, respectively. The most common antibiotic nonsusceptible pattern observed was resistance toward rifampicin [n = 122 (76.25%)] followed by erythromycin [n = 117 (73.12%)]. Among all isolates, gelE [n = 140 (87.5%)], cpd [n = 137 (85.6%)], and asa1 [n = 118 (73.8%)] were the most prevalent virulence genes studied. Thirty isolates (11 E. faecalis, 19 E. faecium) were found to be resistant to vancomycin, with minimum inhibitory concentration of ≥256 μg/ml. Twenty-seven isolates carried the vanA gene, whereas none of the isolates carried vanB. E. faecalis had a considerable ability to show virulence genes and drug resistance. Emergence of antibiotic-resistant enterococci and the high prevalence of virulence traits in our study could be regarded as an alarming situation.

Visceral leishmaniasis (VL), caused by Leishmania infantum, is endemic in southern Iran. To detect asymptomatic individuals, we used kinetoplast DNA (kDNA) polymerase chain reaction (PCR)-ELISA methods on 388 blood samples of healthy persons in two endemic loci and compared the results with the leishmanin skin test (LST) and the immunofluorescent antibody test (IFAT). kDNA PCR, LST, and IFAT were positive in 95 (24.5%), 132 (34%), and 212 (54.6%) cases, respectively. Fifty-five (21.4%) individuals that were LST negative were PCR positive. All PCR-positive individuals had a titer of >or=1:20, whereas 45% of those that were IFAT positive were PCR positive. For a reliable index of prevalence rate of infection, LST alone is not sufficient and needs to be accompanied by PCR-ELISA. The high rate of kDNA-positive results may indicate the possibility of humans being a reservoir and source of transmission. In endemic areas, kDNA PCR-ELISA is not a reliable test for the diagnosis of active VL.