Size-dependent molecular interaction of nontraditional 2D antibiotics withStaphylococcus aureus.

The application of nanomaterials for their antibacterial properties is the subject of many studies due to antibiotic resistance of pathogen bacteria and the necessity of omitting them from food and water resources. Graphene oxide (GO) is one of the most popular candidates for antibacterial application. However, the optimum condition for such an effect is not yet clear for practical purposes. To shed light on how GO and bacteria interaction depends on size, a wide range of GO flake sizes from hundreds of µm2going down to nano-scale as low as 10 N m2was produced. In anin-vitrosystematic study to inhibitStaphylococcus aureusgrowth, the correlation between GO flake size, thickness, functional group density, and antibacterial activity was investigated. The GO suspension with the average size of 0.05 µm2, in the order of the size of the bacteria itself, had the best bacteriostatic effect onS. aureuswith the minimum inhibitory concentration value of 8 µg ml-1, well within the acceptable range for practical use. The bacteriostatic effect was measured to be a 76.2% reduction of the colony count over 2 h of incubation and the mechanism of action was the wrapping and isolation of cells from the growth environment. Furthermore,in-vivoanimal studies revealed that 16 µg ml-1of the optimum GO has efficient antibacterial performance against the methicillin-resistant strains of the bacteria with an enhanced wound healing rate and tensiometrial parameters which is important for realized targets.

Household contact investigation for the detection of active tuberculosis and latent tuberculosis: A comprehensive evaluation in two high-burden provinces in Iran.

BACKGROUND: Systematic evaluation of household contacts of persons with pulmonary tuberculosis (TB) in low- and middle-income countries is recommended by the World Health Organization (WHO). This study recruited adult household contacts of diagnosed TB patients in two high burden provinces of Iran to estimate the prevalence and incidence of active disease and latent TB infection (LTBI) among individuals exposed to TB cases. METHODS: We conducted a cohort study among adults in household contact with a pulmonary TB index case. All subjects were assessed for active disease through evaluation of symptoms. Tuberculin skin test (TST) and QuantiFERON®-TB Gold Plus (QFT-Plus) were used to define LTBI. These tests were performed at the time of the index TB case diagnosis and repeated if the previous result was negative, at three-, 12-, and 18-months post recruitment. In addition, interferon-γ-induced protein-10 (IP-10) concentrations were measured in QFT-Plus supernatants for all participants three months after diagnosing the index case. RESULTS: A total of 451 individuals who had close contact with 95 active TB patients were enrolled in this study. Five (1.1%) contacts were diagnosed with active TB and 285 (63.2%) were identified with LTBI during our study. The incidence rate of LTBI among adult household contacts of TB index cases was 0.44 per person per year. CONCLUSION: The overall rate of LTBI was high. Systematic screening of all household contacts of pulmonary TB should be expanded in Iran to make the timely achievement of the global end TB strategy feasible.

Detection and distribution of zoonotic pathogens in wild Norway rats (Rattus norvegicus) from Tehran, Iran.

This is the first study on the prevalence of vector-borne zoonotic pathogens found in Rattus norvegicus (R. norvegicus) in urban areas of Tehran, Iran. Serological tests were used to detect IgG antibodies against Coxiella burnetii (C. burnetii) and Rickettsia spp. using a commercial qualitative rat ELISA kit. The frequency of Streptobacillus moniliformis (S. moniliformis) and Bartonella spp. was determined using a conventional PCR method. Molecular detection and characterization of Leptospira spp. were conducted using TaqMan real-time PCR based on lipL32 gene and SecY typing methods. A total of 100 R. norvegicus rats were collected from five regions in Tehran, Iran, and investigated to determine their zoonotic pathogens. S. moniliformis and Bartonella spp. were detected in 23 of 100 (23%) and 17 of 100 (17%) R. norvegicus populations, respectively. The highest prevalence of S. moniliformis and Bartonella spp. with similar frequency rates (n = 6/20; 30%) was seen among the R. norvegicus rats captured from the northern and southern parts of Tehran, respectively. Seroreactivity against C. burnetii and Rickettsia spp. was detected in 4% and 1% of R. norvegicus, respectively. C. burnetii. was identified only in one rat captured from the eastern part of Tehran. Results showed that Leptospira spp. was detected only in two rats, collected from the southern part (n = 2/20; 10%) of Tehran. The secY typing method identified two different Leptospira species including L. interrogans and L. kirschneri. The results showed that urban rats might play an important role in transmission of zoonotic pathogens to humans.

Multicentre study of the main carbapenem resistance mechanisms in important members of the Enterobacteriaceae family in Iran.

Resistance to carbapenems has been increasingly reported from the Enterobacteriaceae family, with different mechanisms in different geographic parts of the world. This study investigated the mechanisms of carbapenem resistance in Escherichia coli, Klebsiella pneumoniae and Enterobacter spp. carried out as a multicentre study (n = 10). All third-generation cephalosporin-resistant E. coli, K. pneumoniae and Enterobacter spp. that had been recovered from the selected provinces were included. Modified Hodge test and Carba NP test were done as a phenotypical method for detection of carbapenemase; the most common carbapenemase was detected by PCR. We evaluated the presence of an active efflux pump by using cyanide 3-chlorophenylhydrazone. Overexpression of AcrA/B and presence of OqxAB was detected by real-time PCR and conventional PCR respectively. Microorganisms in this study included 58 E. coli, 95 K. pneumoniae and 60 Enterobacter spp. Modified Hodge test showed a sensitivity of 41% and a specificity of 83%, and the Carba NP test showed a sensitivity of 26% and a specificity of 92% for detection of carbapenemase. OXA-48 was the most frequently detected carbapenemase, followed by NDM-1. Thirty-nine percent and 27% of positive cyanide 3-chlorophenylhydrazone test organisms included active AcrA/B and OqxAB efflux pumps respectively. The result showed the Carba NP test was more specific than MHT. Data confirmed the involvement of AcrA/B and OqxAB efflux pump as a carbapenem resistance mechanism in selected bacteria. Similar to other reports from the Middle East, we found OXA-48 and NDM-1 to be the most frequent carbapenemase.

Characterization of aminoglycoside resistance mechanisms in Acinetobacter Baumannii isolates from burn wound colonization.

Clinical isolates of Acinetobacter baumannii have a tendency to develop antimicrobial resistance against commonly prescribed antimicrobial agents, including aminoglycoside agents, particularly in hospitalized patients worldwide. Resistance mechanisms of the bacterium to aminoglycosides are diverse and commonly involve production of aminoglycoside-modifying enzymes and efflux systems. The aim of this study was to investigate the frequency of gene encoding aminoglycoside-modifying enzymes and expression level of adeB efflux gene in A. baumannii isolates recovered from burn wound colonization. A total of 47 clinical isolates of A. baumannii were obtained from burned patients admitted to the Burns Teaching Hospital, Tehran, in 2018. Standard antimicrobial susceptibility screening was performed to determine resistance pattern. A polymerase chain reaction (PCR) assay was performed to determine aminoglycoside-modifying genes ACC(6'), aph(3')-Via, aph(3')-IIb, aadA1, aphA1 and aph6. Semi-quantitative RT-PCR was also carried out to quantify the expression level of the adeB gene. According to the results of the present study, the acc(6') was the predominant aminoglycoside-modifying enzyme gene (80.9%), followed by aph(3')-via, aph6, aph(3')-IIb and aphA1, which was detected in 59.6%, 42.6%, 14.9% and 14.9% of isolates, respectively. None of the A. baumannii isolates harboured the aadA1 gene. The up regulation of adeB gene expression was observed in 63.8% of strains. Moreover, we indicated that there is a relationship between adeB expression and high resistance to gentamicin. Our results revealed that aminoglycoside resistance could be explained by the production of one or a combination of known aminoglycoside-modifying enzymes rather than overexpression of adeB.

Acinetobacter baumannii (AB) est de plus en plus fréquemment isolé de prélèvements cliniques de par le monde. Il est très susceptible de développer des résistances aux antibiotiques, parmi lesquels les aminosides, en particulier dans les hôpitaux. Les mécanismes sont variables, le plus souvent enzymatiques ou par efflux. Le but de cette étude était d'évaluer les fréquences des gènes codant pour des enzymes modifiant les aminosides et le niveau d'expression du gène de pompe d'efflux adeB chez 47 AB isolés de zones brûlées dans le CTB du CHU de Téhéran. Les gènes codant pour AAC(6'), aph(3')-Via, aph(3') IIb, aadA1, aphA1 et aph6 ont été recherchés par PCR. Le niveau d'expression du gène adeB a été étudié par PCR semi-quantitative : aac(6') était le gène le plus fréquemment retrouvé (80,9%), suivi par aph(3')-Via (59,6%), aph6 (42,6%), aph(3') IIb (14,9%) et aphA1 (14,9%). Nous n'avons pas mis en évidence aadA1. Une surexpression de adeB a été observée chez 63,8 % des souches, reliée à une résistance élevée à la gentamicine. Ces résultats montrent que la résistance de AB aux aminosides est plus d'origine enzymatique que liée à un efflux.

Role of efflux pumps in reduced susceptibility to tigecycline in Acinetobacter baumannii.

Acinetobacter baumannii is an important human pathogen responsible for a various type of infections. These bacterial strains are generally resistant to numerous antibiotics. Therefore, eradication of such strains is problematic and related to high mortality. We investigated the effect of cyanide 3-chlorophenylhydrazone (CCCP) efflux pump inhibitor in tigecycline-resistant strains of Acinetobacter baumannii. In a cross-sectional study, from July until the end of February 2017, eighty isolates of A. baumannii were recovered. Antimicrobial susceptibility testing against tigecycline was performed by the disc diffusion method and determination of minimum inhibitory concentration by broth microdilution method, according to Clinical and Laboratory Standards Institute guidelines. Active efflux pumps were detected by CCCP as an efflux pumps inhibitor, and the gene expression of some of the resistance/nodulation/division (RND)-type efflux pumps was measured by semiquantitative RT-PCR (qRT-PCR). Antibiotic susceptibility tests in this study showed that 78 of 80 A. baumannii isolates were resistant to tigecycline. The results of phenotypic detection of efflux pumps revealed that 23.07% of tigecycline-resistant A. baumannii isolates can contain active efflux pumps. On the basis of conventional PCR, genes coding for adeF and adeJ were detected in 76 (98%) A. baumannii isolates. The results of qRT-PCR showed that the transcript level of the adeJ gene increased in 66.6% A. baumannii isolates with CCCP-positive tests and was correlated with tigecycline resistance. The results of this study indicate that RND-type efflux pumps appear to play a significant role in the tigecycline resistance of A. baumannii.

Nosocomial infections among burn patients in Teheran, Iran: a decade later.

The aim of this study was to determine the epidemiology of nosocomial infections among burn patients in a tertiary burn care centre in Tehran, Iran. A cross-sectional study was carried out during a 6-month period from August 2010 to January 2011 at Motahari Burn and Reconstruction Center in Tehran. Of 155 patients, 677 samples of wound and blood were taken for culture during the course of hospitalization. The rate of positive culture during the 1(st), 2(nd), 3(rd), and 4(th) week of hospitalization were 76.3%, 99.3%, 100%, and 100%, respectively. On the 2(nd), 3(rd), and 4(th) week of hospitalization, Pseudomonas aeruginosa was the most common pathogen followed by Acinetobacter, while the culture positive rate for Staphylococcus spp., Enterobacteriaceae, and Enterococcus spp. significantly decreased (P < 0.001). In this study, 70 patients out of 155 (45.2%) had at least one Acinetobacter positive culture. Our results showed that P. aeruginosa is still the leading cause of nosocomial infections. Additionally, Acinetobacter has appeared as an emerging nosocomial pathogen, and should be considered as a serious risk. We believe that changes in burn wounds' bacterial colonization over time require consistent assessment and monitoring of these changes in any burn center.

KPC-producer gram negative bacteria among burned infants in Motahari Hospital, Tehran: first report from Iran.

To the best of our knowledge, this is the first report of Klebsiella, Acinetobacter and Pseudomonas-producing Klebsiella pneumoniae Carbapenemase (KPC) among burn infants in Iran. The objective of this study was to determine the phenotypic detection of these KPC among isolated Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella spp. A cross-sectional study was performed (February to September 2011) at a tertiary burn hospital in Tehran, Iran. Sixty-four strains were isolated from 20 patients. Strain and genus of isolates were confirmed, antibiotic susceptibility testing was implemented, and KPC determined by Modified Hodge Test. Fifteen of 36 strains (six Pseudomonas aeruginosa, six Acinetobacter baumannii, and three Klebsiella pneumoniae) were resistant to imipenem. Ten strains of 36 Gram negative isolates were resistant to all tested antibiotics except for Colistin. Thirteen of 15 resistant imipenem strains were confirmed as KPC-producer bacteria that isolated from nine patients. Six of 36 isolated strains were extended-spectrum ß-lactamase (ESBL)-producing bacteria, of which four strains were both KPC and ESBL. A high percentage of multidrug resistant (MDR) strains in our centre with positive KPC have created a major challenge in terms of mortality and morbidity. The findings of this study highlight the importance of implementing an effective infection control strategy to prevent and decrease the prevalence of KPC-producing organisms.

Phenotypic screening of extended-spectrum ß-lactamase and metallo-ß-lactamase in multidrug-resistant Pseudomonas aeruginosa from infected burns.

Pseudomonas aeruginosa is an important opportunistic pathogen causing nosocomial infections, especially in immunocompromised patients such as burn patients. Pseudomonas aeruginosa is potentially resistant to different broad-spectrum antibiotics due to its ability to produce extended-spectrum ß-lactamase (ESBL) and metallo-ß-lactamase (MBL). In the present 6 month study, 220 strains of multidrug-resistant (MDR) Pseudomonas aeruginosa were isolated from male and female burn patients who had been hospitalized for at least one week in Motahari Hospital in Tehran. These strains were screened by the disc diffusion and double disc methods to determine the capacity of producing ESBL and MBL. Of all strains, 18% were ESBL-positive, resulting in a significant inhibition zone (≥5 mm) with cefotaxime and ceftazidime plus clavulanic acid discs when compared to the plain cefotaxime or ceftazidime discs. 38% of the strains were MBL-positive, showing at least 7 mm difference between the inhibition zone around the imipenem discs alone in comparison with imipenem plus EDTA discs, and at least 5 mm difference between the inhibition zone around imipenem plus EDTA discs and EDTA discs alone. In the light of our results, the rapidly spreading resistance among bacterial populations due to the extensive use of antibiotics is a matter of concern for the optimal treatment of patients, particularly in burn wards, and the determination of ESBL and MBL production of MDR Pseudomonas aeruginosa strains is essential.