The efficacy of apramycin use in animals: A scoping review.

Vaccine approaches for multidrug resistant Gram negative infections

Antibacterial efficacy of fractions and compounds from Indigofera barberi: Identification of DNA gyrase B inhibitors through pharmacophore based virtual screening

Background Increasing rates of antibiotic resistance has emerged as one of the top concerns in health care. New resistance mechanisms such as carbapenemase production present a challenge in treating common infections. Novel antibiotics are being developed to tackle these pathogens, and one of the newest drugs in this arsenal is cefiderocol, a siderophore cephalosporin. Real-world data regarding the clinical use and outcomes of cefiderocol is limited. Methods A single-center, retrospective chart review was completed from July 2020 to March 2022 and included adult patients who received at least one dose of cefiderocol. Patient baseline characteristics were obtained along with other variables related to the primary infection. The primary outcome was clinical failure defined as 30 day mortality following cefiderocol administration. Secondary outcomes were development of resistance to cefiderocol, clearance of bacteremia, adverse drug reactions, and hospital length of stay. Results Cefiderocol was dispensed in 22 unique patient encounters. It was most often used to treat respiratory tract (45.4%, 10/22) and cardiac device infections (40.9%, 9/22). Most infections were polymicrobial, however, the most common organisms isolated were Pseudomonas aeruginosa and Klebsiella pneumoniae. The clinical failure rate was 22.7% (5/22). One patient developed resistance to cefiderocol throughout the hospitalization. Eight patients were treated for bacteremia, and 87.5% (7/8) demonstrated microbiological cure. Minimal side effects were observed in this cohort; two patients developed diarrhea, and one of whom had confirmed C. difficile colitis. The median length of stay was 24 days. Conclusion This cohort of patients demonstrated that cefiderocol can be used in a variety of multidrug resistant infections including bacteremia. Although limited by a small sample size, this study demonstrated a low prevalence of resistance. These results are promising in the ongoing and emerging issue of antibiotic resistance, and larger studies are needed to determine true efficacy and place in therapy for cefiderocol. Disclosures All Authors: No reported disclosures.

Background: Carbapenems are β-lactam antibiotics, presently considered as the most potent agents for the treatment of multi drug resistant gram negative bacterial infection. Their clinical usage is under threat due to growing incidence of resistance due to production of Carbapenemases which belong to Class B β-lactamases. Knowledge of resistance patterns for Carbapenems will help to guide appropriate and judicious antibiotic use. Hence this study was conducted to detect the resistance to Carbapenems in ESBL producing isolates of E. coli, as the growing incidence of Carbapenem resistance is a major concern to public health. Objectives: 1. Screening and phenotypic confirmation of ESBL production in E. coli isolates. 2. Screening for Carbapenem resistance in ESBL producing E. coli isolates. Materials and Methods: Clinical samples consisting of all exudates, sterile body fluids and urine samples were included in our study. Samples were processed and E. coli identified as per routine laboratory protocol. ESBL screening and phenotypic confirmation, followed by screening for Carbapenem resistance was done as recommended by CLSI guidelines 2014. Results: We isolated 100 ESBL producing E. coli from the samples which were further screened for Carbapenem resistance. Among 100 ESBL producing E. coli isolates, 4(4%) showed Carbapenem resistance, out of which 2 were isloated from urine, 1 each from pus and stool. Co-resistance was observed to other antibiotics including other Cephalosporins(91%), Ampicillin(100%), Piperacillin(95%) and Fluoroquinoles(70%). Conclusion: Our study highlights an increase in resistance pattern in ESBL producing E. coli isolates towards Carbapenems, which is an alarming situation to microbiologists and clinical physicians of our country. Hence, there is a need to emphasize on rational use of antimicrobials and prevent their misuse which is harmful to both patient and community. Keywords: Carbapenemase, β-lactam, ESBL, E. coli, C

Colistin (polymixin E) is an antibiotic prescribed with resurging frequency for multidrug resistant gram negative bacterial infections. It is associated with nephrotoxicity in humans in up to 55% of cases. Little is known regarding genes involved in colistin nephrotoxicity. A murine model of colistin-mediated kidney injury was developed. C57/BL6 mice were administered saline or colistin at a dose of 16 mg/kg/day in 2 divided intraperitoneal doses and killed after either 3 or 15 days of colistin. After 15 days, mice exposed to colistin had elevated blood urea nitrogen (BUN), creatinine, and pathologic evidence of acute tubular necrosis and apoptosis. After 3 days, mice had neither BUN elevation nor substantial pathologic injury; however, urinary neutrophil gelatinase-associated lipocalin was elevated (P = 0.017). An Illumina gene expression array was performed on kidney RNA harvested 72 h after first colistin dose to identify differentially expressed genes early in drug treatment. Array data revealed 21 differentially expressed genes (false discovery rate < 0.1) between control and colistin-exposed mice, including LGALS3 and CCNB1. The gene signature was significantly enriched for genes involved in cell cycle proliferation. RT-PCR, immunoblot, and immunostaining validated the relevance of key genes and proteins. This murine model offers insights into the potential mechanism of colistin-mediated nephrotoxicity. Further studies will determine whether the identified genes play a causative or protective role in colistin-induced nephrotoxicity.

BackgroundPatients in pediatric intensive care Units (PICU) are susceptible to infections with antibiotic resistant organisms which increase the morbidity, mortality and cost of care.To describe the clinical characteristics and mortality in patients with Multi-Drug Resistant (MDR) gram negative organisms. We also report safety of Polymyxin B use in these patients.MethodsFiles of patients admitted in PICU of Aga Khan University Hospital, from January 2010 to December 2011, one month to 15 years of age were reviewed. Demographic and clinical features of patients with MDR gram negative infections, antibiotic susceptibility pattern of isolates, discharge disposition and adverse effects of Polymyxin B were recorded.ResultsA total of 44.8/1000(36/803) admitted patients developed MDR gram negative infections, of which 47.2%(17/36) were male, with mean age of 3.4 yrs(+/−4.16). Acinetobacter Species (25.5%) was the most frequently isolated MDR organisms followed by Klebsiella Pneumoniae (17%). Sensitivity of isolates was 100% to Polymyxin B, followed by Imipenem (50%), and piperacillin/tazobactem (45%). The crude mortality rate of patients with MDR gram negative infections was 44.4% (16/36). Fourteen of 36 patients received Polymyxin B and 57.1%; (8/14) of them were cured. Nephrotoxicity was observed in 21.4% (3/14) cases, none of the patients showed signs of neuropathy.ConclusionOur study highlights high rates of Carbapenem resistant gram negative isolates, leading to increasing use of Polymyxin B as the only drug to combat against these critically ill children. Therefore, we emphasizeon Stewardship of Antibiotics and continuous surveillance system as strategies in overall management of these critically ill children.

ABSTRACT:&#x0D; Background: Failure of treatment with antibiotics occurs due to increase in number of Multidrug resistant gram negative bacteria, worldwide. The objective of this study was to find out the antimicrobial activity of crude ethanolic extract and its further three fractions by Ocimum basilicum leaves against multi drug resistant gram negative rods.&#x0D; Material and Methods: This descriptive study was conducted in the Department of Microbiology, University of Health Sciences, Lahore from 1st july 2016 to 30th june 2017. Total 80 multidrug resistant gram negative rods were included in this study. Agar dilution method was performed to determine MIC of crude ethanolic extract and different fractions i-e n-hexane, chloroform and ethyl acetate of Ocimum basilicum leaves against multidrug resistant gram negative rods i-e ESBLs and carbapenemase producers. Muti-inoculater was used for inoculation.&#x0D; Results: The mean MICs of crude ethanolic extract, n-hexane fraction, chloroform fraction, and ethyl acetate fraction of Ocimum basilicum against ESBLs were 100.0±8.00, 168.13±8.00, 176.88±8.00 41.75±8.00 respectively. Similarly, the mean MICs of crude ethanolic extract, n-hexane fraction, chloroform fraction, and ethyl acetate fraction of Ocimum basilicum against carbapenemase producers were 77.50±8.00, 113.75±8.00, 132.50±8.00 and 29.50±8.00 respectively.&#x0D; Conclusions: Ethyl acetate fraction and crude ethanolic extract from leaves of Ocimum basilicum showed good antibacterial effectiveness against ESBLs and carbapenem resistant organisms than other fractions. This finding may also promote the effective use of O. basilicum herb and its components in modern medicine.

Epidemiology of multi drug resistant gram negative bacteria in Kathmandu, Nepal

Patterns of Infection and Mortality Associated with Intensive AML Induction Therapy: 10 Year Experience from a Tertiary Cancer Centre in India

Impact of COVID-19 pandemic on multidrug resistant gram positive and gram negative pathogens: A systematic review

Background Antimicrobial resistance (AMR) is a complex threat to global health security and universal health coverage. The continued escalation of AMR among Gram-negative bacteria (GNB) is a major concern due to the endemic presence of MDR and extremely drug-resistant (XDR) pathogens.In this regard, the present study aimed to asses the magnitude of MDR, its risk factors, and mortality in MDR/XDR - GNB. Methods GNB isolates were retrieved from patients, identified and assessed for antibiotic resistance pattern using VITEK® 2 compact system. The extended spectrum β-lactamase (ESBL) production in 100 GNB isolates was determined by double disk synergy test and genes confirmed by PCR in retrospective cohort study (2011-2012). The carbapenemase production in 100 isolates was confirmed by modified carbapenem inactivation method in prospective cross-sectional study (2021-2022). The metallo β-lactamase (MBLs) were screened by combined disk test and carbapenemase genes detected by multiplex-PCR. Minimum inhibitory concentration (MIC) of colistin was determined by Broth Micro dilution method and clonal relatedness was evaluated by Multilocus sequence typing (MLST). Results In retrospective study, all cases confirmed ESBL with high incidence of antibiotic resistance in cephalosporins,chloramphenicol and ciprofloxacin. All isolates were susceptible to carbapenem. bla TEM and bla CTX-M were prevalent ESBL genes, with 7 % mortality. In prospective study, isolates were positive for carbapenemase with XDR pattern and 47% of mortality. 90% isolates were MBLs positive and 30% had at least two carbapenemase genes, the combination of bla OXA-48 and bla NDM-1 was highly prevalent. Colistin resistance was observed in 20% and 30% isolates with 8 and 4 µg/ml MICs, respectively. Further, multiplex-PCR confirmed the mcr genes and clonal relatedness was determined. Conclusion The high prevalence rate of MDR-GNB from producing ESBLs (2011-12) to carbapenemase (2021-2022) was observed. Our results emphasize on antibiotic stewardship policies and regular surveillance programmes for monitoring AMR and screening of drug resistance genes. MLST, molecular surveillance, is valuable tool for rapid epidemiological investigation with precision in determining clonal relatedness Disclosures All Authors: No reported disclosures

Use of an Electronic Surveillance System to Further Refine MDRO Isolation Categorization

Objectives: The aim of this work was to determine the antibacterial activity of methanol extract of herbal plants against the Multidrug resistant (MDR) Gram negative bacteria isolated from clinical samples.&#x0D; Methods: Gram negative bacteria isolated from various clinical samples were processed for antibiotic susceptibility test by modified Kirby-Bauer disc diffusion method and MDR bacteria were selected. Methanol extracts of six different medicinal plants Acorus calamus (bojho), Ocimum sanctum (tulsi), Azadirachta indica (neem), Cinnamomum tamala (tejpatta), Aloe vera and Zanthoxylum alatum (timur), were tested for antibacterial activity against the selected MDR bacteria by agar well diffusion method.&#x0D; Results: From clinical samples, 8 different MDR Gram negative bacteria isolated were Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Citrobacter spp., Proteus mirabilis, Proteus vulgaris, Acinetobacter spp. and Pseudomonas spp. with E. coli dominated the number. Out of six medicinal plants extracts, Z. alatum, C. tamala and Ocimum sanctum were found to be effective with zones of inhibition ranging from 9-13 mm. The medicinal plants with antibacterial activity can be an alternative source of medicine against MDR Gram negative bacteria.&#x0D; Conclusion: Several herbal plants extracts exhibit antibacterial activity against MDR Gram negative bacteria. Antibacterial activity of plant extracts can vary with type of plant and extraction methods. Thus, for optimal benefit of plant extract, an appropriate extraction method and use of purified product is essential.

Contemporary emergence of multidrug resistance (MDR) urges regular updates on circulating pathogens and their antimicrobial resistance profiles. We aimed to identify the burden of MDR and World Health Organization (WHO) priority Gram negative pathogens among patients admitted with febrile illness to Abbassia Fever Hospital, a major Public Fever Hospital in Egypt. The carbapenemase- and extended spectrum beta-lactamases (ESBLs)-encoding genes carried by the isolates were also identified. A total of 9602 clinical specimens were collected from febrile patients during 2018 and 2019. The recovered bacterial isolates were examined for antimicrobial susceptibility using disk diffusion test. Susceptibility to colistin was tested using E-test. ESBLs production was phenotypically and genotypically analyzed. A total of 790 bacterial isolates (612 Gram negative and 178 Gram positive) were recovered. A percentage of 77.6%, and 62.9% of the Gram negative and positive isolates showed MDR phenotype, respectively. WHO priority pathogens were abundant, including carbapenem-resistant (CR) Enterobacterales (105/187; 56.1%) and CR glucose non-fermenters (82/187; 43.8%) such as: A. baumannii (55; 29.4%), P. aeruginosa (27; 14.4%). Carbapenemase- and ESBLs-encoding genes were detected in 56.1% and 30.8% of Enterobacterales and in 43.8% and 46.3% of glucose non-fermenters, respectively. Antimicrobials such as fosfomycin and chloramphenicol retained good activities against MDR Gram negative pathogens. This study highlights the regional burden of MDR and priority Gram negative pathogens. The obtained data are of relevant medical importance for implementation of evidence-based antimicrobial stewardship programs and for tailoring the existing empirical treatment guidelines.

Objectives: Surgical infection remains a main cause of death after heart surgery, in spite of the advances in pharmacological therapy. Daptomycin (Dap) is a cyclic lipopeptide antibiotic, useful in gram(+) organisms resistant to standard treatment, including vancomycin. Our aim was to describe the use of Dap in patients with multi-drug resistant gram(+) infections after heart surgery. Methods: 50 consecutive patients presenting with resistant gram(+) infections after heart surgery and treated with Dap (loading dose 6mg/kg/d BW; maintenance 4mg/kg/d BW) were retrospectively studied. Demographics, surgical procedure, type of infection, responsible pathogen, outcome, and adverse events were analyzed. Results: 50 patients (44 males, 5 females; mean age 62±15 y) were studied; Procedure: CABG: 12%; HTX: 10%; VAD: 20%; combined procedures 20%, valve surgery: 10%; others: 28%), Type of infection: catheter-related infection: 45%, sternal wound infection: 20%, Pacemaker-wire infection: 5%, others 30%. The initial Dap dose was 6mg/kg, continued with 4mg/kg. Duration of treatment was 10.6±10d. Pathogens were MSSA 4%, MRSA 14%, S. epidermidis 35%, E. faecium 12%, others 13%, no pathogen found 22%. 88% of the patients showed clinical improvement, in 76% of the patients healing without residues could be achieved. No adverse events were reported. Conclusions: Daptomycin proved safe and effective in our patients. The most common indications were catheter-related infections and sternal wound infections. Prospective trials are mandatory to evaluate the role of Dap, especially in patients with sternal wound infection, caused by multi-drug resistant gram(+) pathogens.