Incidence Of Multidrug Resistance Research Articles

Nano vs Resistant Tuberculosis: Taking the Lung Route.

Tuberculosis (TB) is among the top 10 infectious diseases worldwide. It is categorized among the leading killer diseases that are the reason for the death of millions of people globally. Although a standardized treatment regimen is available, non-adherence to treatment has increased multi-drug resistance (MDR) and extensive drug-resistant (XDR) TB development. Another challenge is targeting the death of TB reservoirs in the alveoli via conventional treatment. TB Drug resistance may emerge as a futuristic restraint of TB with the scarcity of effective Anti-tubercular drugs. The paradigm change towards nano-targeted drug delivery systems is mostly due to the absence of effective therapy and increased TB infection recurrent episodes with MDR. The emerging field of nanotechnology gave an admirable opportunity to combat MDR and XDR via accurate diagnosis with effective treatment. The new strategies targeting the lung via the pulmonary route may overcome the new incidence of MDR and enhance patient compliance. Therefore, this review highlights the importance and recent research on pulmonary drug delivery with nanotechnology along with prevalence, the need for the development of nanotechnology, beneficial aspects of nanomedicine, safety concerns of nanocarriers, and clinical studies.

Multidrug-resistant E. coli encoding high genetic diversity in carbohydrate metabolism genes displace commensal E. coli from the intestinal tract.

Extra-intestinal pathogenic Escherichia coli (ExPEC) can cause a variety of infections outside of the intestine and are a major causative agent of urinary tract infections. Treatment of these infections is increasingly frustrated by antimicrobial resistance (AMR) diminishing the number of effective therapies available to clinicians. Incidence of multidrug resistance (MDR) is not uniform across the phylogenetic spectrum of E. coli. Instead, AMR is concentrated in select lineages, such as ST131, which are MDR pandemic clones that have spread AMR globally. Using a gnotobiotic mouse model, we demonstrate that an MDR E. coli ST131 is capable of out-competing and displacing non-MDR E. coli from the gut in vivo. This is achieved in the absence of antibiotic treatment mediating a selective advantage. In mice colonised with non-MDR E. coli strains, challenge with MDR E. coli either by oral gavage or co-housing with MDR E. coli colonised mice results in displacement and dominant intestinal colonisation by MDR E. coli ST131. To investigate the genetic basis of this superior gut colonisation ability by MDR E. coli, we assayed the metabolic capabilities of our strains using a Biolog phenotypic microarray revealing altered carbon metabolism. Functional pangenomic analysis of 19,571 E. coli genomes revealed that carriage of AMR genes is associated with increased diversity in carbohydrate metabolism genes. The data presented here demonstrate that independent of antibiotic selective pressures, MDR E. coli display a competitive advantage to colonise the mammalian gut and points to a vital role of metabolism in the evolution and success of MDR lineages of E. coli via carriage and spread.

Spatial Analysis of the Occurrence of Multi-Drug Resistance (MDR) Escherichia coli in Pet Dogs in Kupang City

Spatial Analysis of the Occurrence of Multi-Drug Resistance (MDR) Escherichia coli in Pet Dogs in Kupang City

Impact of antimicrobial stewardship on antibiogram, consumption and incidence of multi drug resistance

IntroductionAntimicrobial stewardship programs are intended to improve patient outcomes, reduce side effects, bacterial resistance, and costs. Thus, it is important to assess their impact on an ongoing basis. We aimed to assess the impact of the antimicrobial stewardship program in two different hospitals which used different program approaches.MethodologyThis is a retrospective observational study in two private hospitals [4088 patient records] in Amman- Jordan. Antibiotic susceptibility using antibiogram results, consumption of antibiotics using Defined Daily Dose, and the incidence of Multi-Drug Resistance were recorded using patients’ records during 2018, 2019, and 2020.ResultsAntimicrobial stewardship program outcomes varied between the two hospitals. Bacterial susceptibility to antibiotics were improved in both hospitals. Moreover, the defined daily dose in Hospital “A” showed no significant change in Fluoroquinolones, Carbapenems, and Piperacillin- Tazobactam, Cephalosporins, and Colistin, while a significant change was observed among Anti-MRSA antibiotics. Finally, the incidence of Extended Spectrum Beta-lactamase [ESBL] E. coli, ESBL Klebsiella, and Vancomycin Resistant Enterococci [VRE] have decreased numerically over the study period, while Methicillin-Resistant Staphylococcus aureus [MRSA] showed an increase in incidence during the second year of the study.ConclusionThe study emphasizes the positive impact of the AMS program throughout the three years of the study. Plus, the need to enhance the program through recruiting extra staff and applying extra regulations like implementing educational programs for the hospital staff, designing local guidelines for common ID diseases, and monitoring the program’s outcomes which would eventually be more efficient, cost-effective, and safe.

631 A Comparison of the Microbiology Profile for Two-Stage Revision Surgery in Periprosthetic Joint Infection (PJI) of Primary Knee Arthroplasty and Lower Limb Endoprostheses for Tumour Surgery

Abstract Aim To compare the microbiology organisms responsible for PJI in patients who underwent two-stage revision of infected primary knee replacement with two-stage revision of infected oncological endoprostheses of the lower limb in a single institution. Method 118 patients were treated with 2-stage revision surgery for infected knee arthroplasty and lower limb endoprostheses between 1999 and 2019. 74 patients had two-stage revision for PJI of knee arthroplasty and 44 had two-stage revision to eradicate infection of lower limb endoprostheses for tumour resection. All microbiological data from the first stage sampling was collected and analysed retrospectively. Patient host and extremity criteria were categorised according to the MSIS Host and Extremity Staging System. Results According to the MSIS Staging System, the host and extremity grade of the knee arthroplasty PJI cohort were significantly better than endoprostheses PJI(p<0.05). The incidence of multi-drug resistance (MDR) was higher, 36% in the endoprosthetic group compared to 17% in the infected primary knee replacement group (p=0.001). MDR was most common in coagulase-negative staphylococcus. Gram-positive organisms were isolated in more than 80% of cultures from both cohorts. Coagulase-negative staphylococcus (CoNs) was the commonest gram-positive organism and E Coli was the commonest Gram-negative organism in both groups. Conclusion Patients presenting with PJI after lower limb endoprostheses have a higher incidence of MDR organisms compared to an arthroplasty cohort. Pre-operative microbiological sampling and meticulous sampling methods intra-operatively are extremely important in these patients.

Multidrug-Resistant and Extended-Spectrum β-Lactamase Gram-Negative Bacteria in Bilateral Lung Transplant Recipients: Incidence, Risk Factors, and In-Hospital Mortality

In recent decades, the incidence of multidrug-resistant (MDR) and extended-spectrum β-lactamase (ESBL) gram-negative (GN) bacteria has increased progressively among lung transplantation (LT) recipients. A prompt diagnosis, prevention, and management of these pathogens remain the cornerstone for successful organ transplantation. What are the incidence of MDR and ESBL GN bacteria within the first 30days after LT and related risk of in-hospital mortality? What are the potential clinical predictors of isolation of MDR and ESBL GN bacteria? All consecutive LT recipients admitted to the ICU of the University Hospital of Padua (February 2016-December 2021) were screened retrospectively. Only adult patients undergoing the first bilateral LT and not requiring invasive mechanical ventilation, extracorporeal membrane oxygenation, or both before surgery were included. MDR and ESBL GN bacteria were identified using invitro susceptibility tests and were isolated from the respiratory tract, blood, urine, rectal swab, or surgical wound or drainage according to a routine protocol. One hundred fifty-three LT recipients were screened, and 132 were considered for analysis. Median age was 52 years (interquartile range, 41-60 years) and 46 patients (35%) were women. MDR and ESBL GN bacteria were identified in 45 patients (34%), and 60%of patients demonstrated clinically relevant infection. Pseudomonas aeruginosa (n= 22 [49%]) and Klebsiella pneumoniae (n= 17 [38%]) were frequently isolated after LT from the respiratory tract (n= 21 [47%]) and multiple sites (n= 18 [40%]). Previous recipient-related colonization (hazard ratio [HR], 2.48 [95%CI, 1.04-5.90]; P= .04) and empirical exposure to broad-spectrum antibiotics (HR, 6.94 [95%CI, 2.93-16.46]; P< .01) were independent predictors of isolation of MDR and ESBL GN bacteria. In-hospital mortality of the MDR and ESBL group was 27%(HR, 6.38 [95%CI, 1.98-20.63]; P< .01). The incidence of MDR and ESBL GN bacteria after LT was 34%, and in-hospital mortality was six times greater. Previous recipient-related colonization and empirical exposure to broad-spectrum antibiotics were clinical predictors of isolation of MDR and ESBL GN bacteria.

Serotyping and antibiotic susceptibility pattern of Salmonella serovars from children diagnosed of typhoid fever in Lagos, Nigeria

Typhoid fever is a major health problem in developing countries especially in Nigeria where this infectious disease is endemic, with more concern in children. This prospective study was conducted in 3 Primary Health Centres on children diagnosed clinically of typhoid fever between January, 2017 and December, 2019. The aim of this study was to determine the incidence of Salmonella serovars and antibiotic susceptibility pattern from faecal specimens of children diagnosed clinically based on symptoms of typhoid fever, while demographic information was recovered from their case notes and their mothers. The children were randomly selected having obtained informed consent from their mothers. Four hundred and twenty (420) stool specimens of children aged between 6 months and five years were cultured and serotyped using standard microbiological procedures for isolation and characterization of Salmonella and other enteric bacterial pathogens. The bacteria were isolated by using cultural methods on selective media using a series of biochemical tests and confirmed by using Microgen identification kits and API20E. Serological tests were carried out on suspected Salmonella and Vibrio isolates. Antibiotic susceptibility of the bacterial isolates was determined by using the Kirby-Bauer disc diffusion technique. Bacteriological analysis of the faecal specimens revealed a total of 381 bacterial isolates, among which were 180 (42.9%) Salmonellae. Salmonella enteritidis was the most frequently isolated serovar, 84 (22%), followed by S. typhi, 56 (14.7%), S. paratyphi A, 30(7.9%), and S. typhimurium 10 (2.6%). Other bacteria recovered from the children included Shigella dysenteriae, 64 (16.8), Proteus mirabilis, 60(15.8%), Klebsiella oxytoca, 15(3.9%), Klebsiella ozaenae, 12( 3.2%) and Vibrio parahaemolyticus, 10(2.6%) shows that the Salmonellae and other enteric bacteria showed sensitivity ranging from 70-96% for ampicillin, ciprofloxacin (83.3%-96.4%), gentamicin (56-97.5%), sparfloxacin (83.3-100%), ceftriaxone (83.3-96%) and cefuroxime (80-94%). They were however highly resistant to ampiclox, amoxicillin, and septrin which are over-the-counter drugs. The high incidence of multidrug resistance among Salmonellae and corresponding multidrug resistance among other enteric bacteria, thus posing problems of treatment failures are of great public health significance in a developing country like Nigeria.

Bi-directional elucidation of Lactiplantibacillus plantarum (RTA 8) intervention on the pathophysiology of gut-brain axis during Salmonella brain infection

BackgroundThere have been reports of patients suffering from typhoid fever, particularly those involving infants and immunocompromised patients, which at times present with Salmonella induced brain infection. Although rare, it has frequently been associated with adverse neurological complications and increased mortality. In this context, the gut-brain axis, involving two-way communication between the gut and the brain, holds immense significance as various gut ailments have been associated with psychiatric complications. In turn, several neurodegenerative diseases have been associated with an altered gut microbiota profile. Given the paucity of effective antimicrobials and increasing incidence of multi-drug resistance in pathogens, alternate treatment therapies such as probiotics have gained significant attention in the recent past.ResultsIn the current study, prophylactic effect of Lactiplantibacillus plantarum (RTA 8) in preventing neurological complications occurring due to Salmonella brain infection was evaluated in a murine model. Along with a significant reduction in bacterial burden and improved histoarchitecture, L. plantarum (RTA 8) administration resulted in amelioration in the level of neurotransmitters such as serotonin, norepinephrine and dopamine in the gut as well as in the brain tissue. Simultaneously, increased gene expression of physiologically essential molecules such as mucin (MUC1 and MUC3) and brain-derived neurotrophic factor (BDNF) was also observed in this group.ConclusionPresent study highlights the potential benefits of a probiotic supplemented diet in improving various aspects of host health due to their multi-targeted approach, thereby resulting in multi-faceted gains.

Clinical Characteristics and Outcomes of Neutropenic Sepsis: A Multicenter Cohort Study.

Sepsis is a leading cause of mortality in patients with neutropenia; however, data on whether neutropenic sepsis is associated with distinct clinical characteristics and outcomes are limited. Thus, this study was designed to clarify the clinical characteristics and outcomes of patients with neutropenic sepsis compared with those of patients without neutropenic sepsis diagnosed based on the Third International Consensus Definitions for Sepsis and Septic Shock criteria. We analyzed data from the Korean Sepsis Alliance, a nationwide prospective multicenter cohort study evaluating the clinical characteristics, management, and outcomes of patients with sepsis from September 2019 to February 2020. Eligible patients were divided into the neutropenic (absolute neutrophil count of less than 1,500/mL) and non- neutropenic groups. The characteristics and outcomes were compared between the two groups. During the study period, 2,074 patients were enrolled from 16 tertiary referral or university-affiliated hospitals. Of them, 218 (10.5%) had neutropenia. The neutropenia group was younger and had a lower proportion of patients with chronic diseases compared with the non-neutropenia group. However, solid tumors (50.0% vs. 34.1%; P > 0.001) and hematological malignancies (40.8% vs. 3.8%; P < 0.001) were more common in the neutropenia group. The neutropenia group had a higher incidence of septic shock (43.6% vs. 22.9%; P < 0.001) and higher Sequential Organ Failure Assessment score (7 vs. 5; P < 0.001) than the nonneutropenia group. However, no significant differences in microbiologically confirmed infections and its pathogen distribution and the incidence of multidrug resistance were observed between the two groups. The neutropenic group had a higher hospital mortality than the non-neutropenic group (42.2% vs. 26.3%; P < 0.001), and the Kaplan-Meier survival curve demonstrated a significant difference in survival within 1 week after diagnosing sepsis (log-rank test, P = 0.002). The incidence of adverse events during intensive care unit admission was not different between the two groups. Among hospital survivors, the neutropenic group was more frequently discharged to home (72.2% vs. 57.8%; P = 0.002). Neutropenic sepsis is associated with a higher-grade organ dysfunction during the diagnosis of sepsis and higher mortality without difference in the pathogen isolated.

598. A 3-Year Evaluation of Antibiotic Resistance Patterns in Gram-Negative Genitourinary Tract Infections Treated in Outpatient Infusion Centers (POICs)

BackgroundResistant Gram-negative pathogens (GNP) are common causes of genitourinary tract infections (GUI) often requiring outpatient parenteral antibiotic therapy (OPAT). Data are sparse regarding antibiotic resistance of GNP in patients (pts) treated with OPAT. We analyzed GNP of GUI pts treated in Infectious Disease OICs over a 3-year period stratified by location prior to OPAT.MethodsRecords from 18 POICs were queried for GUI pts with ≥1 GNP receiving OPAT from 2018 to 2020. Demographics, pt location prior to OPAT, infection type, year of therapy, and GNP were recorded. Antibiotic resistance patterns were defined as extended-spectrum beta-lactamase (ESBL) or multi-drug resistant (MDR). Chi Square and Fisher’s exact test were used to determine if ESBL status was associated with GNP or location prior to OPAT (hospital vs. community). The Cochran-Armitage test was used to analyze temporal trend in ESBL expression. Statistical significance was defined as P< 0.05 for all tests. ResultsA total of 634 GNP were identified in 601 pts (mean age: 64±16, 58% female). Infections were 75% complicated urinary tract infection, 20% pyelonephritis, and 5% prostatitis/other. Overall, 56% (n=339) were treated directly from the community and 44% (n=262) following hospital discharge. GNP isolated were 56% E. coli, 19% Pseudomonas spp., 16% Klebsiella spp. and 9% others. Of the 611 GNP with potential to express ESBL, 43% (n=265) were ESBL producers (Table 1). Significantly more ESBL-producing GNP occurred in pts discharged from a hospital prior to OPAT compared to the community (53% vs. 36%, P< 0.001). Overall, the incidence of MDR constituted 36% (n=231) of GNP, which did not differ by location prior to OPAT. Evaluation of ESBL incidence by year showed a significant increase from 2018 to 2020 (P=0.03). Although a slight increase in MDR was noted from 2018 to 2020, this was not significant (Figure 1).Table 1. Frequency of ESBL and MDR by Location prior to OPAT Figure 2. Prevalence of ESBL producers and MDR Pathogens by Year ConclusionResistant GNP were observed in the OPAT setting for GUI with both ESBL and MDR pathogens. We saw a significantly higher rate of ESBL with GNP from hospital discharged pts compared to community-acquired infections and an increase in the overall incidence of ESBL over time. Management of Gram-negative genitourinary infections in the OPAT setting requires close monitoring of emerging resistance patterns. Disclosures Kimberly A. Couch, PharmD, MA, FIDSA, FASHP, AbbVie (Speaker's Bureau) Lucinda J. Van Anglen, PharmD, Merck & Co. (Research Grant or Support)

High prevalence of multidrug-resistant non-fermentative Gram-negative bacilli harboring bla IMP-1 and bla VIM-1 metallo-beta-lactamase genes in Birjand, south-east Iran.

Background and Objectives:Non-fermentative Gram-negative Bacilli (NFGNB) is known as a major cause of healthcare-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 blaIMP, blaVIM, and blaNDM 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 blaIMP-1 and blaVIM-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.

Bloodstream infections in adult patients with malignancy, epidemiology, microbiology, and risk factors associated with mortality and multi-drug resistance

BackgroundThis study aimed to investigate the epidemiology, microbiology, and risk factors associated with mortality and multi-drug resistance bacterial bloodstream infections (BSIs) among adult cancer patients in Shiraz, Iran. We also report a four-year trend of antimicrobial resistance patterns of BSIs.MethodsWe conducted a retrospective study at a referral oncology hospital from July 2015 to August 2019, which included all adults with confirmed BSI.Results2393 blood cultures tested during the four-year study period; 414 positive cultures were included. The mean age of our patients was 47.57 ± 17.46 years old. Central Line-Associated BSI (CLABSI) was more common in solid tumors than patients with hematological malignancies. Gram-negative (GN) bacteria were more detected (63.3%, 262) than gram-positive bacteria (36.7%, 152). Escherichia coli was the most common gram-negative organism (123/262, 47%), followed by Pseudomonas spp. (82/262, 31%) and Klebsiella pneumoniae (38/262, 14.5%). Coagulase-negative staphylococci (CoNS) was the most frequently isolated pathogen among gram-positive bacteria (83/152, 54.6%). Acinetobacter spp., Pseudomonas spp., E. coli, and K. pneumoniae were the most common Extended-Spectrum Beta-Lactamase (ESBL) producers (100, 96.2, 66.7%, and 60.7, respectively). Acinetobacter spp., Pseudomonas spp., Enterobacter spp., E. coli, and K. pneumoniae were the most common carbapenem-resistant (CR) isolates (77.8, 70.7, 33.3, 24.4, and 13.2%, respectively). Out of 257 Enterobacterales and non-fermenter gram-negative BSIs, 39.3% (101/257) were carbapenem-resistant. Although the incidence of multi-drug resistance (MDR) gram-negative BSI increased annually during 2015–2018, the mortality rate of gram-negative BSI remains unchanged at about 20% (p-value = 0.55); however, the mortality rate was significantly greater (35.4%) in those with resistant gram-positive BSI (p-value = 0.001). The overall mortality rate was 21.5%. Early (7-day mortality) and late mortality rate (30-day mortality) were 10 and 3.4%, respectively.ConclusionsThe emergence of MDR gram-negative BSI is a significant healthcare problem in oncology centers. The high proportion of the most frequently isolated pathogens were CR and ESBL-producing Enterobacterales and Pseudomonas spp. We have few effective choices against MDRGN BSI, especially in high-risk cancer patients, which necessitate newer treatment options.

Novel Applications of Nanotechnology in Controlling HIV and HSV Infections.

Infectious diseases have been prevalent for many decades and viral pathogens have caused global health crises and economic meltdown on a devastating scale. The high occurrence of novel viral infections in recent years, in spite of the progress achieved in the field of pharmaceutical sciences, defines the critical need for newer and more effective antiviral therapies and diagnostics. The incidence of multi-drug resistance and adverse effects due to the prolonged use of anti-viral therapy is also a major concern. Nanotechnology offers a cutting edge platform for the development of novel compounds and formulations for biomedical applications. The unique properties of nano-based materials can be attributed to the multi-fold increase in the surface to volume ratio at the nano-scale, tunable surface properties of charge and chemical moieties. Idealistic pharmaceutical properties such as increased bioavailability and retention times, lower toxicity profiles, sustained- release formulations, lower dosage forms and most importantly, targeted drug delivery can be achieved through the approach of nanotechnology. The extensively researched nano-based materials are metal and polymeric nanoparticles, dendrimers and micelles, nano-drug delivery vesicles, liposomes and lipid-based nanoparticles. In this review article, the impact of nanotechnology on the treatment of Human Immunodeficiency Virus (HIV) and Herpes Simplex Virus (HSV) viral infections during the last decade is outlined.

Clinical characteristics and outcome of bacteraemia caused by Enterobacter cloacae and Klebsiella aerogenes: more similarities than differences

The genus Enterobacter is a common cause of nosocomial infections. Historically, the most frequent Enterobacter species were those of Enterobacter cloacae complex and Enterobacter aerogenes. In 2019, E. aerogenes was re-classified as Klebsiella aerogenes owing to its higher genotypic similarity with the genus Klebsiella. Our objective was to characterise and compare the clinical profiles of bacteraemia caused by E. cloacae and K. aerogenes. This 3-year multicentre, prospective cohort study enrolled consecutive patients with bacteraemia by E. cloacae or K. aerogenes. Baseline characteristics, bacteraemia features (source, severity, treatment), antibiotic susceptibility, resistance mechanisms and mortality were analysed. The study included 285 patients with bacteraemia [196 (68.8%) E. cloacae and 89 (31.2%) K. aerogenes]. The groups showed no differences in age, sex, previous use of invasive devices, place of acquisition, sources or severity at onset. The Charlson score was higher among patients with E. cloacae bacteraemia [2 (1-4) vs. 1 (0.5-3); P=0.018], and previous antibiotic therapy was more common in patients with K. aerogenes bacteraemia (57.3% vs. 41.3%; P=0.01). Mortality was 19.4% for E. cloacae and 20.2% for K. aerogenes (P = 0.869). Antibiotic susceptibility was similar for both species, and the incidence of multidrug resistance or ESBL production was low (6% and 5.3%, respectively), with no differences between species. Bacteraemias caused by E. cloacae and K. aerogenes share similar patient profiles, presentation and prognosis. Patients with E. cloacae bacteraemia had more co-morbidities and those with K. aerogenes bacteraemia had received more antibiotics.

Nanovectorization of Prostate Cancer Treatment Strategies: A New Approach to Improved Outcomes.

Prostate cancer (PC) is the most frequent male cancer in the Western world. Progression to Castration Resistant Prostate Cancer (CRPC) is a known consequence of androgen withdrawal therapy, making CRPC an end-stage disease. Combination of cytotoxic drugs and hormonal therapy/or genotherapy is a recognized modality for the treatment of advanced PC. However, this strategy is limited by poor bio-accessibility of the chemotherapy to tumor sites, resulting in an increased rate of collateral toxicity and incidence of multidrug resistance (MDR). Nanovectorization of these strategies has evolved to an effective approach to efficacious therapeutic outcomes. It offers the possibility to consolidate their antitumor activity through enhanced specific and less toxic active or passive targeting mechanisms, as well as enabling diagnostic imaging through theranostics. While studies on nanomedicine are common in other cancer types, only a few have focused on prostate cancer. This review provides an in-depth knowledge of the principles of nanotherapeutics and nanotheranostics, and how the application of this rapidly evolving technology can clinically impact CRPC treatment. With particular reference to respective nanovectors, we draw clinical and preclinical evidence, demonstrating the potentials and prospects of homing nanovectorization into CRPC treatment strategies.

High incidence of multidrug resistance and class 1 and 2 integrons in Escherichia coli isolated from broiler chickens in South of Iran.

The objective was to investigate the multidrug resistance and presence of class 1 and 2 integrons in 300 Escherichia coli isolates obtained from 20 broiler farms during three rearing periods (one-day-old chicks, thirty-day-old chickens, and one day before slaughter) in Fars, South Iran. Results showed that 81.00%, 82.00%, and 85.00% of isolates were multidrug-resistant on the first day, thirty-day-old chickens, and one day before slaughter, respectively. Multidrug-resistant E. coli isolates were further examined for the presence of class 1 and 2 integrons using PCR assay. The existence of class 1 integron-integrase gene (intI1) was confirmed in 68.40%, 72.70%, and 60.90% of multidrug-resistant isolates from stage 1, stage 2, and stage 3 of the rearing period, respectively. The frequency of class 2 integron-integrase gene (intI2) during the first to the third stage of sampling was 2.60%, 25.50%, and 30.40%. Also, sequence analysis of the cassette arrays within class 1 integron revealed the presence of the genes associated with resistance for trimethoprim (dfrA), streptomycin (aadA), erythromycin (ereA), and orfF genes. The results revealed that percentages of antimicrobial resistance in E. coli isolates were significantly higher in the middle and end stages of the rearing period. In conclusion, widespread dissemination of class 1 integrons in all three stages and rising trends of class 2 integrons existence in E. coli isolates during the rearing period of broiler chickens could exacerbate the spread of resistance factors among bacteria in the poultry industry. Future research is needed to clarify its implication for human health.

IN VITRO SCREENING OF COLIPHAGE EFFICACY AGAINST MULTIDRUG DRUG RESISTANT CLINICAL ISOLATES OF ESCHERICHIA COLI

The incidence of multi-drug resistance (MDR) in bacteria has become a major problem in this era of modern medicine, making it necessary to look for other options that can be used to treat the infections caused by the MDR bacteria. Scientifically, one of the therapies that is now looking promising, is application of phage therapy. This research work was designed to determine the efficacy of coliphages isolated from sewage, against MDR clinical isolates of E. coli. Ten (10) clinical isolates were subjected to both microbiological conventional and PCR techniques for confirmation, thereafter, the confirmed isolates were tested against some 8 commonly used antibiotics using disk diffusion method to identify the MDR among them. The MDR isolates were subjected to various dilutions (1:10-1:108) of coliphage recovered from sewage, sampled from 5 different locations and isolated by using double agar overlay method. Out of the 10 isolates collected, 8(80%) were confirmed as E. coli, all (8/8: 100%) of which were MDR. However, 6(75%) out of the 8 MDR E. coli, were lysed by the coliphages-observed as cytopathic effect in form of clear zones (plaques) within the bacterial lawn and were recorded from all the dilutions (100%) tested and from all the locations (100%) sampled. Conclusively, infection by MDR E. coli may be life threatening, as it is highly prevalent (100% in our study). However, the coliphages were found to be abundant in sewage and the application of their therapy may provide a good alternative treatment against the MDR.

A prospective study on microbiological profile and antimicrobial resistance pattern in chronic suppurative otitis media at a rural centre

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Over and injudicious prescription of antibiotics over the years has resulted in change in microbial flora in chronic suppurative otitis media (CSOM). More over the incidence of multidrug resistance in bacteria is increasing alarmingly. This study was done to know the microbial pattern in CSOM in the current scenario. This study also aims to know the microbial resistance pattern and the drug sensitivity, also how to tackle the growing multidrug resistance in current practice.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; Sterile swab was collected from 100 patients who attended Outpatient Department of our hospital during 1 year period, sent for culture sensitivity. Details like age distribution, sex distribution, microbial pattern, MDR susceptibility pattern were evaluated. &lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; Males were commonly affected. Most common age group was in the 5&lt;sup&gt;th&lt;/sup&gt; decade followed by 4&lt;sup&gt;th&lt;/sup&gt; decade. Staphylococcus aureus was the most common pathogen followed by &lt;em&gt;Pseudomonas&lt;/em&gt;. All the multi drug resistant (MDR) strains were &lt;em&gt;Pseudomonas&lt;/em&gt;, and were sensitive to only higher antibiotic like Piperaziccilin Tazobactam (PTZ), Imipenem (IMP) with 2 of them only intermediate sensitivity to IMP.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Staph aureus and &lt;em&gt;Pseudomonas&lt;/em&gt; are the most common pathogen in CSOM. Incidence of MDR is on the rise even to higher line drugs. Hence pus culture and sensitivity should be made mandatory in every case of CSOM before starting higher antibiotics or putting patient on long term treatment. This will prevent the emergence of multidrug resistant strains.&lt;/p&gt;

Molecular characterisation of an Acinetobacter baumannii outbreak

SummaryBackgroundAcinetobacter baumannii are problematic hospital pathogens, and the increased incidence of multi drug resistance has significantly limited treatment options. The global epidemiology is not fully characterised due to large data gaps from low- and middle-income countries. This study characterised the molecular epidemiology of an A. baumanniii outbreak in Egypt.MethodsFifty-four A. baumannii isolates were recovered from a 4-month-outbreak at Tanta University Hospitals (TUH). Associated clinical and demographic data, and the antibiograms were analysed, and Carbapenem resistant isolates were screened for acquired carbapenemase genes by PCR and sequencing. Epidemiological typing was performed by single-locus sequencing of blaOXA-51-like and Multi Locus Sequence Typing (MLST), and sequence types (STs) were analysed based on maximum-likelihood phylogeny (PhyML) to identify relatedness.FindingsImmune suppression and ICU admission were the most common co-morbidity and risk factor. Carbapenem resistance accounted for 81%, and correlated with the presence of OXA-23, NDM-1 and -2, and VIM-1 and -2 carbapenemases. Nine different blaOXA-51-like genes were identified which corresponded to 22 different Sequence Types (STs), including 10 novel. International clone (IC2) was the predominant clone. PhyML analysis revealed the presence of 2 distinct clones with multiple sub-lineages.ConclusionGiven the short duration of the study, there was a rare heterogeneous population in the hospital. Carbapenem resistance is mediated by acquired carbapenemases in diverse lineages indicating the possibility of horizontal gene transfer. The diversity indicates the influx of multiple lineages of IC2 into TUH from unknown sources. Molecular epidemiological studies are essential for infection prevention and control measures.

Incidence and Risk Factors Associated with Multi-Drug-Resistant Pathogens in a Critically Ill Trauma Population: A Retrospective Cohort Study.

Background: Multi-drug resistance is considered a serious health threat particularly in the intensive care unit (ICU) setting. Studies evaluating multi-drug-resistant (MDR) pathogens in critically ill trauma patients are limited. The objectives were to describe the incidence of MDR, extensive-drug-resistant (XDR), and pan-drug-resistant (PDR) organism growth in ICU patients admitted with traumatic injuries and to identify any risk factors associated with MDR growth. Patients and Methods: This was a retrospective single-center cohort study of all ICU adult patients identified via the institution's trauma registry from January 1, 2016 to August 31, 2017. Patients were included if they had positive culture growth with susceptibility data taken during the index hospitalization. Patients were excluded if their cultures were drawn within 48 hours of emergency department triage. Study groups were defined based on the presence of at least one MDR pathogen during the index hospitalization. Results: A total of 2,578 charts were reviewed and 95 patients (mean age, 60 years; 66 males [69%]) with 201 total cultures were included. The majority of positive cultures were from respiratory (69%) and urinary (16%) sources. Of the 201 positive cultures, the majority of species identified was Enterobacteriaceae (47%), Staphylococcus (32%), Enterococcus (7%), Acinetobacter (5%), and Pseudomonas (3%). Of the 95 patients with positive cultures, the incidence of MDR, XDR, and PDR organisms was found to be 31%, 17%, and 0%, respectively. Augmented renal clearance (ARC) was the only risk factor associated with an increased risk for MDR organism growth (adjusted odds ratio 9.78, 95% confidence interval [CI] 2.56-37.41; p = 0.001). Conclusions: In this cohort of critically ill trauma patients, the incidence of an MDR pathogen occurred in 31% of patients. This is the first study to find an association of ARC and multi-drug resistance, which should be further validated as a potential cause for MDR organisms.