The emergence of Escherichia coli sequence type 131 (ST131) as a multidrug-resistant and virulent pathogen represents a major challenge to public health globally. Recently, the O25b/ST131 E. coli producing CTX-M-15 with high virulence potential has been reported worldwide, but has received little attention in Iran. This study is the first in Iran to specifically determine the spread of the O25b/ST131 clone producing CTX-M-15 among E. coli isolates belonging to the B2 phylogenetic group. ST131 clone in phylogenetic group B2 was detected based on PCR detection of ST131-specific single-nucleotide polymorphisms in mdh and gyrB. O25b/ST131 E. coli clone was confirmed utilizing O25b/ST131 clone allele-specific PCR for the pabB gene. All group B2 E. coli isolates were characterized based on antibiotic susceptibility, extended-spectrum b-lactamase (ESBL) enzymes, and virulence traits. Our results demonstrated that 38 out of the 154 B2 group isolates (24.7%) were identified as belonging to the ST131 clone. Furthermore, of these, 28 isolates (73.6%) were detected as O25b/ ST131 clone. Antibiotic resistance of ST131 E. coli isolates to ciprofloxacin, gentamicin, cefotaxime, and aztreonam was significantly higher than non-ST131 isolates. Almost all of the O25b/ST131 isolates with the ability for ESBL production were reported as CTX-M-15 producing (95.5%). Our results showed that the most prevalent virulence trait in ST131 clone was ompT (94.7%). This study is the first to report the prevalence of the CTX-M-15-producing O25b/ST131 E. coli in Iran. Our findings reinforce the surveillance of dissemination of ST131 E. coli clone as a major drug-resistant pathogen and an important new public health threat.

Background Melittin is one of the most studied antimicrobial peptides, and several in vitro experiments have demonstrated its antibacterial efficacy. However, there is evidence showing melittin has non-promising effects such as cytotoxicity and hemolysis. Therefore, concerns about unwanted collateral toxicity of melittin lie ahead in the path toward its clinical development. With these considerations, the present study aimed to fill the gap between in vitro and in vivo studies. Methods In the first step, in vitro toxicity profile of melittin was assessed using cytotoxicity and hemolysis tests. Next, a maximum intraperitoneal (i.p.) sub-lethal dose was determined using BALB/c mice. Besides toxicity, antimicrobial efficacy of melittin against extensively drug-resistant (XDR) Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA), and KPC-producing Klebsiella pneumonia (KPC-KP) pathogens were tested using both in vitro and in vivo methods. Results Melittin showed extensive hemolysis (HD50 = 0.44 µg/mL), and cytotoxicity (IC50 = 6.45 µg/mL) activities with i.p. LD50 value of 4.98 mg/kg in BALB/c mice. In vitro antimicrobial evaluation showed melittin MIC range from 8 to 32 µg/mL for the studied pathogens. Treatment of infected mice with repeated sub-lethal doses of melittin (2.4 mg/kg) displayed no beneficial effect on their survival and peritoneal bacterial loads. Conclusions These results indicate that melittin at its safe dose could not exhibit antimicrobial activity, which hinders its application in clinical practice.

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Background and Objectives: Non-fermentative Gram-negative Bacilli (NFGNB) is known as a major cause of health- care-associated infections with high levels of antibiotic resistance. The aim of this study was to investigate the antibiotic resistance profiles and molecular characteristics of metallo-beta-lactamase (MBL)-producing NFGNB. Materials and Methods: In this cross-sectional study, the antibiotic resistance profile of 122 clinical NFGNB isolates was determined by the Kirby-Bauer disk diffusion and microdilution broth methods. Bacterial isolates were investigated for the detection of MBLs production using the combination disk diffusion Test (CDDT). The existence of bla , bla , and bla NDM genes in all carbapenem-resistant isolates was determined employing polymerase chain reaction (PCR) assays. Results: High resistance in Pseudomonas aeruginosa was reported to cefotaxime and minocycline, whereas Acinetobacter baumannii isolates were highly resistant to all antibiotics except colistin. Multidrug resistance (MDR)-NFGNB (66% vs. 12.5%, P=0.0004) and extensively drug resistant (XDR)-NFGNB (55.7% vs. 12.5%, P=0.001) isolates were significantly more common in hospitalized patients than in outpatients. The production of MBL was seen in 40% of P. aeruginosa and 93.3% of A. baumannii isolates. It was found that 33.3% and 46.7% of carbapenem-resistant P. aeruginosa isolates, and 13.3% and 28.9% of carbapenem-resistant A. baumannii isolates were harboring bla IMP-1 and bla VIM-1 genes, respectively. The incidence of MDR (98.2% vs. 28.3%, P<0.001) and XDR (96.4% vs. 11.7%, P<0.001) in MBL-producing NFGNB isolates was significantly higher than non-MBL-producing isolates. Conclusion: This study demonstrated a higher rate of resistance among NFGNB isolates with an additional burden of MBL production within them, warranting a need for robust microbiological surveillance and accurate detection of MBL producers among the NFGNB.

Background: This research aimed to estimate the prevalence of extended-spectrum b-lactamase-producing Enterobacteriaceae (ESBL-PE) in stool samples of patients with different types of cancer. Materials and Methods: Stool samples or deep rectal swabs were collected from cancer cases from January 2017 to December 2018. After species identification, in order to detect ESBL-PE, double-disk synergy test (DD test) was used. Disk diffusion procedure was conducted to determine the susceptibility of bacteria to antimicrobials. Lastly, antibiotic resistance genes including bla genes were characterized via polymerase chain reaction (PCR). Findings: Among 100 patients enrolled in this study, 50 (50%) were ESBL carriers. Escherichia coli was the most prevalent bacterium isolated (85%). Genotyping of EBSL-PE encoding genes using PCR showed that the prevalence rates of bla CTX-M and bla CTX-M-15 genes were 94 (47 of 50) and 90% (45 of 50), respectively, which were higher than those of bla TEM (80%, 40 of 50) and bla SHV genes (34%, 17of 50). There was no significant association between ESBL-PE fecal carriage and age (p= .68), sex (p = .49), time of diagnosis (p= .21), antibiotic therapy for the past three months (p= .77), and history of chemotherapy (p= .49). Finally, it was determined that cancer type was an associated risk factor for ESBL-PE fecal carriage in cancer patients. Conclusion: This research emphasizes regular bacterial monitoring, and that antibiotic stewardship plans ought to be performed among cancer patients to prohibit further spread of ESBL-PE with confined therapeutic options.

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Backgrounds:The ever-increasing incidence of multidrug resistance in ESBL-producing Pseudomonas aeruginosa is one of the most serious public health threats. This study aimed to investigate the antibiotic resistance profile and molecular characteristics of ESBL-producing P. aeruginosa isolates. Materials & Methods: Antimicrobial susceptibility testing was performed for 120 P. aeruginosa clinical isolates using the Kirby-Bauer disk diffusion and broth microdilution assays. Combined disk test (CDT) was applied to screen for ESBL production among P. aeruginosa isolates. PCR assays determined the presence of bla GES , bla PER , and bla VEB genes in all isolates. Findings: The clinical isolates of P. aeruginosa showed the highest resistance to cefotaxime (86.7%) and gentamicin (65.8%). Of 120 P. aeruginosa isolates, 60.8% were MDR, and 53.3% were XDR. The prevalence of these strains was significantly higher in hospitalized patients than in out-patients (p<.001). Also, 58 P. aeruginosa strains (48.3%) were considered as phenotypic ESBL producers. Furthermore, 15, 35, and 24.2% of P. aeruginosa isolates harbored bla GES , bla VEB , and bla PER , respectively. The incidence of MDR (71.4% vs. 41.9%, p= .001) and XDR (63.6% vs. 34.9%, p= .002) was significantly higher in ESBL-producing P. aeruginosa isolates compared to non-ESBL producers. The highest incidence rate of MDR was reported in bla VEB gene-positive P. aeruginosa isolates (95.2%), followed by isolates harboring bla PER (79.3%) and bla GES (55.6%) genes. Conclusion:This study findings show a high prevalence of MDR ESBL-producing P. aeruginosa isolates, indicating the importance of correct identification of these superbugs and judicious use of various antibiotics to prevent their spread.

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