High Multidrug Resistance Research Articles

Multidrug-Resistant Micro-Organisms Associated with Urinary Tract Infections in Orthopedic Patients: A Retrospective Laboratory-Based Study.

Background: The risk of healthcare-associated infections (HAIs) in surgical wards remains closely related to the type of surgery and procedures performed on patients. Those factors also condition the risk of various forms of clinical infections, especially urinary tract infections (UTIs). UTIs are most frequently (70–80% of cases) caused by the use of bladder catheter in the perioperative period. The aim of this study was to perform an epidemiological and microbiological analysis of UTIs in orthopedic patients, with an emphasis on multidrug-resistant (MDR) micro-organisms. Methods: The study was conducted in a 38-bed Department of Orthopedic-Traumatic Surgery in Sosnowiec, Poland. 5239 patients, operated on in 2013–2015, were included in the study. The urinary catheter use rate was 30.7%. Laboratory-based study used the UTI definition of the HAI-Net program. A micro-organism was declared MDR if it was resistant to at least one antibiotic from three or more groups of antibacterial drugs, and extensively drug-resistant (XDR) if it was sensitive to antibiotics from no more than two groups of drugs. Results: The UTI incidence was 3.2% (168 cases), the CA-UTI incidence density was 9.6/1000 catheter days. The highest risk of UTI was found in patients aged 75 or older. Monomicrobial cultures were detected in 163 specimens (78% of all microbiologically confirmed UTIs). Gram-negative flora prevailed among the micro-organisms, the predominantly isolated Enterobacteriaceae being Escherichia coli and Klebsiella pneumoniae. In 16 patients (7.7% of microbiologically confirmed UTIs), yeast infection was confirmed. Isolated micro-organisms were fully sensitive to carbapenems. Gram-negative bacilli showed the lowest sensitivity to extended substrate spectrum penicillins and fluoroquinolones (37–64%), as well as to trimethoprim-sulfamethoxazole (50%). The MDR prevalence was 24.4%. Conclusions: The presented data indicates that UTIs are a significant problem in the studied population, so is antimicrobial resistance, especially to quinolones, and extended-spectrum cephalosporins, which are often used as first-line therapy. To tackle the problem of high UTI incidence and MDR prevalence, reducing the UTI risk factors should be prioritized.

High Prevalence of blaCTX-M-15 Gene among Extended-Spectrum β-Lactamase-Producing Escherichia coli Isolates Causing Extraintestinal Infections in Bangladesh

The emergence of multidrug-resistant (MDR) Escherichia coli (E. coli) clonal lineages with high virulence potential is alarming. Lack of sufficient data on molecular epidemiology of such pathogens from countries with high infection burden, such as Bangladesh, hinders management and infection control measures. In this study, we assessed the population structure, virulence potential and antimicrobial susceptibility of clinical E. coli isolates from Dhaka, Bangladesh. A high prevalence of MDR (69%) and extended-spectrum β-lactamase production (ESBL) (51%) was found. Most E. coli isolates were susceptible to amikacin (95%), meropenem (94%) and nitrofurantoin (89%) antibiotics. A high prevalence of ST131 (22%) and ST95 (9%) followed by ST69 (4%) and ST73 (3%) was observed. Phylogroups B2 (46%), B1 (16%), D (10%) and F (9%) were prominent. blaCTX-M-15 (52%) and blaNDM-1 (5%) were the most prevalent ESBL and carbapenem resistance genes, respectively. Moreover, the predominant pathotype identified was extraintestinal pathogenic E. coli (ExPEC) (41%) followed by enteric pathogens (11%). In conclusion, our results suggest the transmission of clonal E. coli groups amidst diverse E. coli population that are associated with high virulence potential and MDR phenotype. This is of high concern and mandates more efforts towards molecular surveillance of antimicrobial resistance (AMR) in clinically significant pathogens.

Antimicrobial Activity of Colistin Against Contemporary (2015 - 2017) P. aeruginosa and A. baumannii Isolates From a Chinese Surveillance Program.

ObjectiveTo investigate the incidence and susceptibilities of non-fermenting bacteria isolates from Chinese respiratory (RTI), intra-abdominal (IAI) and urinary tract (UTI) infections to antimicrobial agents between 2015 and 2017.MethodsIn total, 3,246 non-fermentative bacteria were collected from 21 hospitals and 9 hospital departments across 7 regions of China. A central testing laboratory was employed to determine antimicrobial susceptibilities using appropriate standards of interpretation.ResultsThe majority of the isolates were Acinetobacter baumannii (n = 1,360, 41.9%) and Pseudomonas aeruginosa (n = 1,341, 41.3%). Overall multidrug resistance (MDR) and carbapenem resistance (CR) rates of Acinetobacter baumannii were 80.1 and 78.7% with MDR and CR rates in RTIs, IAIs, and UTIs of 82.0 and 81.0%, 82.6 and 81.0% as well as 53.1 and 46.9%. Overall MDR and CR rates of Pseudomonas aeruginosa isolates were 36.2 and 38.9% with 41.8 and 44.3%, 29.3 and 36.1% as well as 24.2 and 20.2% MDR and CR rates in RTIs, IAIs, and UTIs. Overall susceptibility rates to imipenem, meropenem, amikacin, ciprofloxacin, cefepime and piperacillin-tazobactam were 21.1, 21.3, 33.0, 18.4, 19.2, and 19.6% for Acinetobacter baumannii and 56.5, 58.5, 88.4, 63.1, 63.1, and 55.63% for Pseudomonas aeruginosa isolates, whereas for colistin they were 95.7 and 94.6%, respectively. In all departments and regions of China, susceptibility rates of Pseudomonas aeruginosa and Acinetobacter baumannii isolates to colistin were constantly above 80%.ConclusionDue to the high MDR and CR rates for Pseudomonas aeruginosa and Acinetobacter baumannii, isolates obtained from RTIs, IAIs, and UTIs only maintained high susceptibility rates to colistin between 2015 and 2017.

Surveillance of antimicrobial resistance in Escherichia coli and enterococci from food products at retail in Beijing, China

Public health intervention priorities to control the spread of antimicrobial resistance in the food sector rely on a comprehensive understanding of its situation among various food products. By analyzing a set of fifteen different kinds of food products (n = 495) collected at retail in Beijing, China, we found the food-animal products, vegetables, aquatic products and fruits were highly contaminated by E. coli (38.4%, 95% CI: 34.1%-42.8%) and enterococci (74.5%, 95% CI: 70.5%-78.3%), showing a multidrug-resistance (MDR) proportion of 20.3% and 39.5%, respectively. With the highest incidence of E. coli (66.7%, 95% CI: 57.9%-74.6%) and enterococci (80.3%, 95% CI: 72.5%-86.7%), as well as the high MDR proportion; the food-animal products were indeed the most important reservoir of antimicrobial resistance; although the role of vegetables, fruits and aquatic products in the spreading AMR shouldn't be downplayed. These food-borne isolates were highly resistant to antibiotic that are widely used in agriculture, such as tetracycline (E. coli, 65.8%; enterococci, 36.9%) and ampicillin (E. coli, 60.5%), and also to antibiotics that are barely used in the agriculture/aquaculture, such as rifampin (enterococci, 55.3%) and ciprofloxacin (enterococci, 36.9%). Moreover, we observed positive correlations between food types and some particular resistance phenotypes of the isolates. In addition, genes coding resistance to clinical important antibiotics, mcr-1 (colistin) and optrA (oxazolidinones), were detected in the food-borne isolates and showed by bioinformatics analysis a potential in connecting animals and humans.

The Frequency of Resistance Genes in Salmonella enteritidis Strains Isolated from Cattle

Salmonella enteritidis causes infections in humans and animals. Antibiotics are used to eliminate bacterial infections, which become resistant to antibiotics after a while. This study aimed to isolate S. enteritidis from cattle feces samples and also to evaluate the frequency of genes associated with multi-drug resistance (MDR). One hundred ten fecal samples of cattle were collected from Jul to Dec, 2017 in Khuzestan Province, southern Iran. Bacterial culture and molecular methods were used to isolate and identify S. enteritidis. Disk diffusion method was used to assess antibiotic susceptibility. Then Polymerase chain reaction (PCR), assay was used for definitive diagnosis of S. enteritidis and resistance genes. Overall, 101 (91.81%) samples were detected to be contaminated with Salmonella genus and 86 samples (85.14%) were identified as S. enteritidis. The highest and lowest antibiotic resistance were belonged to gentamicin (n=70, 81.39%), and tetracycline (n=6, 6.97%). Besides, 64 samples (74.42%) had 2-10 drugs resistance patterns. Moreover, the highest and the least resistance were related to blaIMP-1 (n=73, 84.88%) and tet(B) (n=49, 56.97%) genes respectively. The drug-induced genes in S. enteritidis have a high frequency. Therefore, antibiotic resistance and high MDR to antibiotics can be due to the incorrect use of antibiotics and the lack of health monitoring in Cattle farms.

Evaluation of type II Toxin-Antitoxin Systems, Antibiotic Resistance Profiles, and Biofilm Quorum Sensing Genes in Acinetobacter Baumannii Isolates in Iraq.

Bacterial Toxin-Antitoxin (TAs) systems are extensive two-component elements in the bacterial genome, which are involved in many key biological functions, including growth arrest, survival, biofilm formation, plasmid maintenance, defense against phages, persistence, and virulence. This study aimed to assess the molecular determinants involved in TAs, biofilm quorum sensing, and antibiotic resistance profiles in Acinetobacter baumannii isolated from Baghdad's hospitals in Iraq. A total of 127 A. baumannii isolates were collected from 2160 different clinical samples. The antimicrobial susceptibility test was performed using the disk diffusion test. All isolates were characterized for molecular determinants involved in TAs and biofilm formation using the wellknown PCR-based sequencing assay. A high multi-drug resistant (MDR) (96.06%; 122/127) and imipenem resistance (84.25%; 107/127) rates were observed from A.baumannii isolates. Results showed the presence of rhlIR gene in three isolates (2.36%), and lasIR gene appeared in two isolates (1.57%) isolates, whilst, mazEF, ccdAB, and relBE genes have not been detected among any of the isolates. A high MDR and imipenem resistance rates within a low prevalence of rhlIR, and lasIR genes could be found in clinical A. baumannii isolates from some of the Iraqi hospitals.

Antibiotic resistance profile of commensal Escherichia coli isolated from healthy sheep in Qatar.

The uncontrolled antibiotics use in livestock is a leading factor for the emergence and spread of resistant bacteria from food animals to humans through the food chain. This study aims at evaluating the magnitude of the antimicrobial resistance (AMR) in food animals, acknowledging the lack of information on the prevalence of resistance in the veterinary field in Qatar. Rectal samples were collected from 171 sheep across three localities in Qatar between December 2016 and July 2017. These rectal samples were suspended in Phosphate buffer solution (PBS). Then streaked onto a selective CHROMagar E. coli medium plates and incubated at 37°C for 18 to 24 h. Isolated E. coli were tested for antibiotic susceptibility against 16 clinically- relevant antibiotics using the E-test method. Statistical analyses were performed using SPSS statistics 24. E. coli was isolated from 144 samples (84.2%), of which 90% were resistant to at least one antibiotic and 44% were multi-drug resistant (MDR). The highest resistance was against ciprofloxacin 69.4% (100), followed by nitrofurantoin 47.2% (68), trimethoprim/sulfamethoxazole 45.8% (66), cephalothin 43% (62) and amoxicillin/clavulanic acid 18% (26). Low resistance was reported to fosfomycin, amikacin and tigecycline 1.4% (2), 0.7% (1), and 0.7% (1), respectively. We reported high MDR E. coli in rectal swabs of sheep in Qatar. Such resistant bacteria can potentially be transmitted to humans, resulting in public health concerns. This requires a quick response to develop and implement a stewardship program for the monitoring of antibiotic use in the veterinary in Qatar.

Antimicrobial resistance pattern of extended-spectrum β-lactamase-producing Escherichia coli isolated from fecal samples of piglets and pig farm workers of selected organized farms of India.

Background and Aim:Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are gradually increasing worldwide and carry a serious public threat. This study aimed to determine the antimicrobial resistance pattern of ESBL-producing E. coli isolated from fecal samples of piglets and pig farm workers.Materials and Methods:Fecal samples from <3-month-old piglets (n=156) and farm workers (n=21) were processed for the isolation of ESBL-producing E. coli in MacConkey agar added with 1 µg/mL of cefotaxime. E. coli (piglets=124; farm workers=21) were tested for ESBL production by combined disk method and ESBL E-strip test. Each of the ESBL-positive isolate was subjected to antibiotic susceptibility testing. The ESBL-producing E. coli were further processed for genotypic confirmation to CTX-M gene.Results:A total of 55 (44.4%, 55/124) and nine (42.9%, 9/21) ESBL-producing E. coli were isolated from piglets and farm workers, respectively. Antibiotic susceptibility testing of the ESBL-positive E. coli isolates from piglets and farm workers showed 100% resistance to ceftazidime, cefotaxime, cefotaxime/clavulanic acid, ceftazidime/clavulanic acid, and cefpodoxime. A proportion of 100% (55/55) and 88.9% (8/9) ESBL-positive E. coli were multidrug resistance (MDR) in piglets and farm workers, respectively. On genotypic screening of the ESBL E. coli isolated from piglets (n=55), 15 were positive for the blaCTX-M gene and of the nine ESBL E. coli from farm workers, none were positive for the blaCTX-M gene.Conclusion:Although there was no significant difference in isolation of ESBL-producing E. coli between piglets and farm workers, the ESBL-positive E. coli from piglets showed relatively higher MDR than farm workers.

Phenotypic characterization of beta-lactamases producing Gram-negative bacteria in a tertiary hospital, Nepal

Infections caused by beta-lactamases producing Gram-negative bacteria are increasing, thus posing a challenge to the management of such infections. The surveillance data of such bacteria is limited in Nepal so this study aimed to detect the beta-lactamase producing Gram-negative bacteria in a tertiary setting. A total of 604 clinical samples, including urine, blood, sputum and body fluids, were cultured and identified by the routine standard laboratory protocols. Antibiotic susceptibility testing was done by Kirby Bauer disc diffusion method following Clinical and Laboratory Standard Institute guidelines (2014). Extended-spectrum beta-lactamases (ESBL) producers were identified by combined disk method and metallo-beta-lactamases (MBL) producers were identified by Imipenem- EDTA combined disk method. Out of 604 samples, 282 (46.7%) samples showed significant growth, of which 229 (81.2%) were Gram-negative bacteria. Of 229 Gram-negative bacteria, 200 (87.3%) were multidrug resistant, 67 (29.3%) were ESBL producers and 16 (7.0%) were MBL producers. Klebsiella pneumoniae were among higher ESBL producers and Pseudomonas aeruginosa were among higher MBL producers. The findings suggest higher antibacterial resistance among Gram-negative bacteria with the added burden of beta-lactamase production. Imipenem was effective against 125 of 229 Gram-negative bacteria tested. Thus, imipenem can be the drug of choice for empirical management. The higher multidrug resistance and higher beta-lactamases production among Gram-negative bacteria warrant the continuous monitoring, surveillance, early detection, and infection control practices of such bacteria

Antimicrobial resistance in fecal Escherichia coli and Salmonella enterica isolates: a two-year prospective study of small poultry flocks in Ontario, Canada

BackgroundAlthough keeping small poultry flocks is increasingly popular in Ontario, information on the antimicrobial susceptibility of enteric bacteria of such flocks is lacking. The current study was conducted on small poultry flocks in Ontario between October 2015 and September 2017, and samples were submitted on a voluntary basis to Ontario’s Animal Health Laboratory. From each submission, a pooled cecal sample was obtained from all the birds of the same species from the same flock and tested for the presence of two common enteric pathogens, E. coli and Salmonella. Three different isolates from each E. coli-positive sample and one isolate from each Salmonella-positive sample were selected and tested for susceptibility to 14 antimicrobials using a broth microdilution technique.ResultsA total of 433 fecal E. coli isolates (358 chicken, 27 turkey, 24 duck, and 24 game bird) and 5 Salmonella isolates (3 chicken, 1 turkey, and 1 duck) were recovered. One hundred and sixty-seven chicken, 5 turkey, 14 duck, and 15 game bird E. coli isolates were pan-susceptible. For E. coli, a moderate to high proportion of isolates were resistant to tetracycline (43% chicken, 81% turkey, 42% duck, and 38% game bird isolates), streptomycin (29% chicken, 37% turkey, and 33% game bird isolates), sulfonamides (17% chicken, 37% turkey, and 21% duck isolates), and ampicillin (16% chicken and 41% turkey isolates). Multidrug resistance was found in 37% of turkey, 20% of chicken, 13% of duck, and 8% of game bird E. coli isolates. Salmonella isolates were most frequently resistant to streptomycin, tetracycline, and sulfonamides. Resistance to cephalosporins, carbapenems, macrolides, and quinolones was infrequent in both E. coli and Salmonella isolates. Cluster and correlation analyses identified streptomycin-tetracycline-sulfisoxazole-trimethoprim-sulfamethoxazole as the most common resistance pattern in chicken E. coli isolates. Turkey E. coli isolates compared to all the other poultry species had higher odds of resistance to tetracycline and ampicillin, and a higher multidrug resistance rate.ConclusionsEscherichia coli isolates were frequently resistant to antimicrobials commonly used to treat poultry bacterial infections, which highlights the necessity of judicious antimicrobial use to limit the emergence of multidrug resistant bacteria.

Triggered ferroptotic polymer micelles for reversing multidrug resistance to chemotherapy

Drug-tolerant persister cancer cells (PCCs) play an important role in the development of multidrug resistance (MDR) to anti-cancer drugs. This is due to the strong link between PCCs formation and epithelial-mesenchymal transition (EMT), as well as the low numbers of PCCs. In addition, PCC removal by traditional cytotoxic agents is poor due to the intrinsic high MDR activity in these cells. As a novel programmed cell death pathway, ferroptosis shows high potency to eliminate cells at the EMT state via manipulating intracellular redox homeostasis. The aim of this work was to utilize triggered ferroptotic polymer micelles for PCCs removal and MDR reversal both in vitro and in vivo. The micelles were made of arachidonic acid-conjugated amphiphilic copolymer that can enable rapid cargo release upon free radical-triggering in the tumor microenvironment. A potent ferroptotic inducer, RSL3 was encapsulated in the micelles to target the glutathione peroxidase 4 (GPX4). In the model resistant human ovarian adenocarcinoma cells, the RSL3 micelles were 30-fold more toxic than activatable control micelles due to the ferroptotic machinery. The lipid peroxidation-induced intracellular glutathione level reduction also made a contribution, which enhanced the potency of RSL3 for ferroptosis induction and enabled the drug-loaded micelles all-active. As an index of PCCs population, the level of CD133+ and aldehyde dehydrogenase (ALDH+) biomarker was significantly lower for the ferroptotic micelles in contrast to the control. The potency of ferroptotic micelles regarding PCCs reduction was proved by the in vitro soft agar colony forming assay. The in vivo anti-tumor efficacy of triggered micelles was further demonstrated in tumor-bearing nude mice in terms of PCCs biomarkers, tumor growth inhibition, mice survival, and GPX4 inhibition. This work demonstrates a novel strategy to overcome cancer MDR via the tailored ferroptotic micelles, which opens new avenues for managing resistant tumors.

English

Staphylococcus aureus is commonly associated with mastitis in dairy herds with potential public health implications. Overall, 303 samples were collected from September 2015 to July 2016 to characterize the phenotypic and genotypic pattern of drug resistance in S. aureus isolated from cases of clinical and sub-clinical bovine mastitis in Central Ethiopia. Milk samples were tested by using California Mastitis Test and positive samples were subjected for bacterial culture, disc diffusion test and polymerase chain reaction (PCR) to detect the presence of antimicrobial resistance. Based on California mastitis test (CMT) result and clinical examination, the prevalence of mastitis was 70.6%. S. aureus was isolated from 36.9% of CMT positive samples. The phenotypic determination of antimicrobial resistance showed that the isolates were most resistant to ampicillin (80%) followed by trimethoprim-sulfamethoxazole (23.3%), tetracycline (15%), streptomycin (10%) and gentamycin (3.3%) and equally to both erythromycin and chloramphenicol (1.6%). Characterization of the antimicrobial resistance gene was done by using PCR. Most of the isolates (56%) contained blaZ gene followed by ermB (33%), ermC (13.3%) and each ermA and msrA appeared only in 2% of the isolates. There was no isolate harboring the methicillin resistance mecA gene. Thirty six percent of the isolates contained more than one antibiotic resistance genes. The highest multidrug resistance (MDR) gene combination was observed by blaZ*ermB (31.25%) genes and the least frequently occurred were blaZ *ermA and msrA*ermB (3.12%) each. This study showed that consumption of raw milk could be considered as a critical source of antibiotic resistant S. aureus. Key words: Bovine mastitis, Staphylococcus aureus, antimicrobial resistance, Ethiopia.

Surprising synergy of dual translation inhibition vs. Acinetobacter baumannii and other multidrug-resistant bacterial pathogens

BackgroundMultidrug-resistant (MDR) Acinetobacter baumannii infections have high mortality rates and few treatment options. Synergistic drug combinations may improve clinical outcome and reduce further emergence of resistance in MDR pathogens. Here we show an unexpected potent synergy of two translation inhibitors against the pathogen: commonly prescribed macrolide antibiotic azithromycin (AZM), widely ignored as a treatment alternative for invasive Gram-negative pathogens, and minocycline, among the current standard-of-care agents used for A. baumannii. MethodsMedia-dependent activities of AZM and MIN were evaluated in minimum inhibitory concentration assays and kinetic killing curves, alone or in combination, both in standard bacteriologic media (cation-adjusted Mueller-Hinton Broth) and more physiologic tissue culture media (RPMI), with variations of bicarbonate as a physiologic buffer. Synergy was calculated by fractional inhibitory concentration index (FICI). Therapeutic benefit of combining AZM and MIN was tested in a murine model of A. baumannii pneumonia. AZM + MIN synergism was probed mechanistically by bacterial cytological profiling (BCP), a quantitative fluorescence microscopy technique that identifies disrupted bacterial cellular pathways on a single cell level, and real-time kinetic measurement of translation inhibition via quantitative luminescence. AZM + MIN synergism was further evaluated vs. other contemporary high priority MDR bacterial pathogens. FindingsAlthough two translation inhibitors are not expected to synergize, each drug complemented kinetic deficiencies of the other, speeding the initiation and extending the duration of translation inhibition as verified by FICI, BCP and kinetic luminescence markers. In an MDR A. baumannii pneumonia model, AZM + MIN combination therapy decreased lung bacterial burden and enhanced survival rates. Synergy between AZM and MIN was also detected vs. MDR strains of Gram-negative Klebsiella pneumoniae and Pseudomonas aeruginosa, and the leading Gram-positive pathogen methicillin-resistant Staphylococcus aureus. InterpretationAs both agents are FDA approved with excellent safety profiles, clinical investigation of AZM and MIN combination regimens may immediately be contemplated for optimal treatment of A. baumannii and other MDR bacterial infections in humans. FundNational Institutes of Health U01 AI124326 (JP, GS, VN) and U54 HD090259 (GS, VN). IC was supported by the UCSD Research Training Program for Veterinarians T32 OD017863.

High incidence of multidrug-resistant Escherichia coli coharboring mcr-1 and bla CTX-M-15 recovered from pigs.

PurposeThe coexistence of mobile colistin (COL)-resistant gene mcr-1 with extended-spectrum beta-lactamase (ESBL) gene in Escherichia coli has become a serious threat globally. The aim of this study was to investigate the increasing resistance to COL and in particular its coexistence with ESBL-producing E. coli recovered from pig farms in China.Materials and methodsE. coli were isolated from 14 pig farms in Jiangsu China. Susceptibility testing was identified by micro-dilution method. PCR assay and nucleotide sequencing were used to detect COL-resistant genes, mcr-1 to −5, as well as ESBL genes, blaCTX-M, blaSHV and blaTEM. Conjugation experiment, plasmid replicon typing of the multidrug resistance (MDR), S1-PFGE and DNA southern hybridization were performed to study the transferability of these genes.ResultsOverall, 275 E. coli isolates were recovered from a total of 432 cloacal and nasal swabs. More than 90% of the isolates were MDR, of which 70.18% were resistant to COL. Of these 275 isolates, mcr-1 was identified as the most predominant gene carried by 71.63% (197/275) of isolates, 39.59% (78/197) of the isolates were harboring both mcr-1 and ESBL genes (blaCTX-M, blaSHV and blaTEM). ESBL genotyping showed that blaCTX-M was the most predominant ESBL (68.49%) followed by blaSHV (16.4%) and blaTEM (15%). Sequencing revealed that the most common variants of blaCTX-M identified were, blaCTX-M-15 (69%), blaCTX-M-55 (29%) and blaCTX-M-1 (1.8%). IncHI2, IncFIB, IncFIC, IncN and IncX4 were found to be the most common Inc-types found both in donors and in transconjugants and were associated with the transfer of the mcr-1 and ESBL encoding genes. Six strains carried a total of five different plasmids: approximately 97-, 130-, 160-, 227- and 242-kb plasmids.ConclusionThe coexistence of the mcr-1- and blaCTX-M-15-carrying isolates displaying high MDR, recovered from E. coli of pig origin, is a major concern for both humans and veterinary medicine.

Epidemiology of urinary tract infection and antimicrobial resistance in a pediatric hospital in Nepal

BackgroundUrinary tract infection is an infection affecting infants and children. The aim of this study was to determine the etiology of urinary tract infection along with their antimicrobial resistance.MethodsThis cross-sectional study was conducted from June 2015 to January 2016 at Siddhi Memorial Hospital, Bhaktapur, Nepal. Urine samples were first cultured on cystine lactose electrolyte deficient agar and blood agar by semi-quantitative technique, and then incubated aerobically for 18–24 h at 37 °C. The identified bacterial isolates were tested for antimicrobial susceptibility by Kirby Bauer disc diffusion technique.ResultsOf 1599 urine samples, 12.3% samples showed significant bacterial growth. E. coli (58.7%) was the most common pathogen, followed by Klebsiella pneumoniae (22.5%). Most of the isolates were resistant to ampicillin and co-trimoxazole, while least were resistant to amikacin and nitrofurantoin. Higher multi-drug resistance (61.9%) was observed among isolates.ConclusionsE. coli and Klebsiella spp. were predominant cause of pediatric urinary tract infection in children. Higher susceptibility observed against aminoglycosides and nitrofurans make these drugs suitable in emergency.

Design, synthesis and biological evaluation of N-(4-(2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)phenyl)-4-oxo-3,4-dihydrophthalazine-1-carboxamide derivatives as novel P-glycoprotein inhibitors reversing multidrug resistance

The overexpression of P-glycoprotein plays an important role in the process of multidrug resistance (MDR). P-gp inhibitors are one of the effective strategies to reverse tumor MDR. Novel P-gp inhibitors with phthalazinone scaffolds were designed, synthesized and evaluated. Compound 26 was found to be the most promising for further study. Compound 26 possessed high potency (EC50 = 46.2 ± 3.5 nM) and low cytotoxicity.26 possessed high MDR reversal activity towards doxorubicin-resistant K56/A02 cells. Reversal fold (RF) value reach to 44.26. 26 also increased accumulation of doxorubicin (DOX or ADM) or other MDR-related anticancer drugs with different structures. In conclusion, compound 26 deserves more research for its good features as P-gp inhibitor.

Drug Resistance Pattern of Bacterial Pathogens of Enterobacteriaceae Family

Objectives: This study was done to determine the drug resistance pattern and Extended Spectrum β-Lactamase (ESBL) in bacterial isolates of Enterobacteriaceae family from different clinical specimens.Methods: The isolates were identified by conventional culture techniques and subjected to antimicrobial susceptibility testing by modified Kirby Bauer disk diffusion methods and ESBL detection by combined disk method.Results: Of the total 1602 sample processed 200 (12.5%) bacteria of Enterobacteriaceae family were isolated and 85.5% of them were multidrug resistant. Of the total Enterobacteriaceae isolates 27% were ESBL producers. Single isolate of stool was MDR and ESBL producer. Higher prevalence of MDR isolates (100%) and ESBL producer (41.2%) was observed in sputum specimen. Higher multidrug resistance (92.1%) and ESBL production (35%) was detected in Klebsiella pneumoniae.Conclusion: The most effective antibiotics towards the isolates of Enterobacteriaceae were imipenem, amikacin, chloramphenicol and tetracycline. Emergence of MDR and ESBL producing Enterobacteriaceae requires proper infection control measures and routine and reliable detection of ESBL with rationale use of antibiotics.

Multidrug Resistance, Biofilm Formation, and Virulence of Escherichia coli Isolates from Commercial Meat and Vegetable Products.

Escherichia coli is an important food safety and public health concern because of its pathogenicity and potential for antimicrobial resistance. E. coli isolates as food contaminants and their antimicrobial resistance, biofilm-forming ability, and virulence genes were analyzed to identify the potential of E. coli in food as a major transmission route for antimicrobial resistance and infectious agents. Among the 709 samples of minced meat and fresh vegetable products tested, 18.6% were positive for E. coli. One hundred nine (29.2%) out of 383 E. coli isolates were resistant to 1 or more of the 25 tested antimicrobials. Among the isolates from minced pork, the highest rate of resistance was observed for tetracycline (52.8%), followed by ampicillin (41.6%). The highest resistance rates against tetracycline were coincident with the high amount of tetracycline sold for veterinary use. Because penicillin is the most frequently used antimicrobial in humans, with 4.52 defined daily doses per 1000 people per day, the high rate of resistance to ampicillin (41.6%) supported the potential risk of E. coli food contaminants. However, only 1.3% of the isolates possessed the virulence genes commonly involved in foodborne outbreaks of E. coli. Sixty-seven isolates (17.5%) were multidrug-resistant (MDR), and the highest MDR was observed against 14 antimicrobials. Most of the MDR E. coli isolates showed biofilm-forming ability. Therefore, these isolates will have additional protection from environmental stresses, including antimicrobials. Given the importance of E. coli to food safety and public health, our results on the prevalence of antimicrobial resistance and virulence factors provide useful information for risk management options to protect public health.

Phenotypic and genotypic characterization of temporally related nontyphoidal Salmonella strains isolated from humans and food animals in central Ethiopia.

Salmonella is one of the common causes of food-borne bacterial illnesses. The primary sources of human nontyphoidal Salmonella (NTS) infection are food animals. This study characterized temporally and spatially related Salmonella isolated during April 2013 to March 2014 from faeces of diarrhoeic human patients in Addis Ababa (n=68) and food animals (n=84) in Addis Ababa and surrounding districts (dairy cattle, n=30; slaughtered cattle, n=20; poultry, n=26; swine n=8). Isolates were serotyped, page typed and tested for antimicrobial susceptibility using Kirby-Bauer disc diffusion method, and genotyped by pulsed-field gel electrophoresis (PFGE). The dominant Salmonella serovars isolated from food animals were S. Saintpaul (38.1%), S. Typhimurium (17.9%) and S. Kentucky (9.5%), whereas in humans, S. Typhimurium (39.7%), S. Virchow (30.9%) and S. Kottbus (10.3%) were frequently isolated. Resistance to streptomycin, sulfisoxazole, tetracycline, ampicillin and cephalothin was higher in animal isolates than human isolates, and mean number of antimicrobials to which isolates were resistant was significantly higher in isolates from cattle and poultry compared to those from humans (p<0.05). All S. Kentucky isolated from animals and humans were multidrug resistant (MDR) with shared resistance phenotype (AmpCfCipTeSuSNa). Although this study involved small sample size and was not able to show clear epidemiological linkage among isolates from various sources, genotyping by PFGE analysis demonstrated circulation of closely related genotypes of S. Virchow, S. Typhimurium and S. Kentucky among humans and food animals. Detection of related Salmonella isolates from humans and animals, the high MDR status of isolates from animals and close proximity of farms and human residential areas in the absence of appropriate biosecurity present major public health problem. Integrated surveillance of Salmonella serovars in humans and animals and implementation of appropriate hazard analysis and pathogen control strategies along critical points of the food chain from farm to table is recommended.

Analysis of Acinetobacter baumannii hospital infections in patients treated at the intensive care unit of the University Hospital, Wroclaw, Poland: a 6-year, single-center, retrospective study.

BackgroundAcinetobacter baumannii (AB) is one of the most frequently isolated strains of bacteria in intensive care unit (ICU) patients, which provides huge therapeutic problems due to its multidrug resistance (MDR).Patients and methodsThe overall purpose of the study was analysis of health care- associated infections in terms of the incidence of AB strain infections and the changing susceptibility of this strain within a 6-year observation (2011–2016). The study was carried out in an ICU of the University Hospital in Wroclaw (Poland).ResultsAmong 589 isolated strains responsible for 540 health care-associated infections (21.2%) in 2549 ICU patients, AB was the pathogen in 183 (31%) cases. The incidence of AB infection amounted to 6.4/1000 patient-days. An increase was noted in the total number of hospital infections caused by AB strain from 16.5% and 3.39/1000 patient-days in 2011 to 41% and 9.64/1000 in 2016 (p=0.0003 and p=0.000, respectively). AB infections most frequently concerned ventilator-associated pneumonia (73.8%). AB was susceptible to colistin, amikacin, imipenem, meropenem, and ciprofloxacin in 100%, 10.7%, 12.3%, 11.5%, and 2.4% respectively, and it was characterized by MDR in 98.36% of the strains.ConclusionThe study revealed a 3-fold increase in the incidence of AB strain infections, significant increase in the resistance to carbapenems in the observed period, and a very high MDR. The solution to this problem would be the implementation of a repair program aiming at inhibition of AB strain transmission, measures to prevent infections, and restricted use of antibiotics.