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Simple Summary: The rise of drug-resistant bacteria, particularly in animals, poses a major challenge in veterinary medicine. Antibiotic development lags behind the increasing resistance. To tackle this, alternative therapies have been explored, such as the use of natural products and plant extracts. This study evaluates the laboratory efficacy of plant derivatives of the Alliaceae group (which includes garlic and onion) as antimicrobial agents, with encouraging results. Although further research is needed, these findings suggest a potential role for these natural compounds in veterinary medicine. Background: The increase of multi-resistant bacteria, especially Staphylococcus spp. and Enterobacteriaceae, constitutes a challenge in veterinary medicine. The rapid growth of resistance is outpacing antibiotic discovery. Innovative strategies are needed, including the use of natural products like Allium species (Allium sativum L. and Allium cepa L.), which have been used empirically for centuries to treat infectious diseases in humans and farm and aquaculture animals due to their antibacterial properties. Methods: This study aimed to evaluate the in vitro activity of two Allium-derived compounds, propyl propane thiosulfinate (PTS) and propyl propane thiosulfonate (PTSO), against multi-resistant Staphylococcus spp. (n = 30) and Enterobacteriaceae (n = 26) isolated from dogs referred to a veterinary teaching hospital in Madrid. Results and Discussion: The results indicated the in vitro efficacy of PTSO/PTS against the tested bacterial strains, and 56.7% of Staphylococcus pseudintermedius and 53.8% of Enterobacteriaceae showed sensitivity to PTS and PTSO compared with classic antibiotics. In addition, 50% of S. pseudintermedius strains resistant to erythromycin, ibofloxacin, difloxacin and orbifloxacin and 50% of Enterobacteriaceae strains resistant to tetracycline and doxycycline were sensitive to PTS and PTSO. Although studies are needed to verify their efficacy in vivo, the combined use of PTS and PTSO exhibits promise in enhancing bacterial sensitivity against S. pseudintermedius and Enterobacteriaceae infections, providing a first insight into the potential of both compounds in veterinary practice. [ABSTRACT FROM AUTHOR]

Background: The increase of multi-resistant bacteria, especially Staphylococcus spp. and Enterobacteriaceae, constitutes a challenge in veterinary medicine. The rapid growth of resistance is outpacing antibiotic discovery. Innovative strategies are needed, including the use of natural products like Allium species (Allium sativum L. and Allium cepa L.), which have been used empirically for centuries to treat infectious diseases in humans and farm and aquaculture animals due to their antibacterial properties. Methods: This study aimed to evaluate the in vitro activity of two Allium-derived compounds, propyl propane thiosulfinate (PTS) and propyl propane thiosulfonate (PTSO), against multi-resistant Staphylococcus spp. (n = 30) and Enterobacteriaceae (n = 26) isolated from dogs referred to a veterinary teaching hospital in Madrid. Results and Discussion: The results indicated the in vitro efficacy of PTSO/PTS against the tested bacterial strains, and 56.7% of Staphylococcus pseudintermedius and 53.8% of Enterobacteriaceae showed sensitivity to PTS and PTSO compared with classic antibiotics. In addition, 50% of S. pseudintermedius strains resistant to erythromycin, ibofloxacin, difloxacin and orbifloxacin and 50% of Enterobacteriaceae strains resistant to tetracycline and doxycycline were sensitive to PTS and PTSO. Although studies are needed to verify their efficacy in vivo, the combined use of PTS and PTSO exhibits promise in enhancing bacterial sensitivity against S. pseudintermedius and Enterobacteriaceae infections, providing a first insight into the potential of both compounds in veterinary practice.

This research aimed to investigate the microbial composition and diversity of antimicrobial resistance genes (ARGs) found in Chinese broiler and layer family poultry farms. We focused on the differences in resistance phenotypes and genotypes of multidrug-resistant Enterobacteriaceae (MDRE) isolated from the two farming environments and the existence and transmissibility of colistin resistance gene mcr-1. Metagenomic analysis showed that Firmicutes and Bacteroides were the dominant bacteria in broiler and layer farms. Many aminoglycoside and tetracycline resistance genes were accumulated in these environments, and their absolute abundance was higher in broiler than in layer farms. A total of 526 MDRE were isolated with a similar distribution in both farms. The results of the K-B test showed that the resistance rate to seven antimicrobials including polymyxin B and meropenem in broiler poultry farms was significantly higher than that in layer poultry farms (P < 0.05). PCR screening results revealed that the detection rates of mcr-1, aph(3')Ia, aadA2, blaoxa-1, blaCTX-M, fosB, qnrD, sul1, tetA, and catA1 in broiler source MDRE were significantly higher than those in layers (P = 0.05). A chimeric plasmid p20432-mcr which carried the novel integron In1866 was isolated from broiler source MDRE. The high frequency of conjugation (10-1 to 10-3) and a wide range of hosts made p20432-mcr likely to play an essential role in the high detection rate of mcr-1, aph(3')-Ia, and aadA2 in broiler farms. These findings will help optimize disinfection and improve antimicrobial-resistant bacteria surveillance programs in poultry farms, especially broilers. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the resistance profile and the prevalence of antibiotic resistance genes in 30 isolates of Klebsiella spp. and Aeromonas spp. recovered from water sold in the streets of Maputo. Susceptibility profiles to 15 antibiotics were performed according to Clinical Laboratory Standard Institute guidelines with antibiotic disks on Mueller-Hinton agar plates. Multiplex PCRs were performed targeting 10 ß-lactamase genes, five ESBL (blaTEM-variants, blaOXA-variants, BlaSHV-variants, MCTX-M Group 1 and Group 9 variants) and five AmpC (ACC variants, FOX variants, MOX variants, CIT variants and DHA variants). The results showed a high prevalence of Klebsiella resistance to ß-lactam antibiotics, such as amoxicillin/clavulanic acid (62.5%), amoxicillin (56.3%), ampicillin (50%), cefoxitin (43.8%), and cefotaxime (43.8%). Aeromonas showed resistance to cefoxitin and ampicillin (71.4%), amoxicillin/clavulanic acid (57.1%) and imipenem (42.9%). ESBL blaOXA-variants, blaSVH-variants, MCTX-M Group 1 variants, and MCTX-M Group 9 variants were the most prevalent b-lactam genes, followed by the b-lactams AmpC, ACC variants and FOX variants. It is extremely important to improve waterborne disease control strategies, especially in terms of public awareness of the potential health implications of multidrug-resistant strains of Klebsiella and Aeromonas, which are often neglected. [ABSTRACT FROM AUTHOR]

This study was conducted to determine the occurrence, antibiotic susceptibility pattern, and plasmid profile of multi drug-resistant (MDR) Enterobacteriaceae isolated from soymilk hawked in the Ibadan Polytechnic Com munity, Nigeria. Bacterial isolation and identification were performed using a culture-dependent method and bio chemical characterization, respectively, while antibiotic susceptibility was tested using the disk diffusion method. Plasmid analysis and curing were performed using standard procedures. The results revealed the following occurrence rate of bacterial species in soymilk samples collected from all axes (South, North, East, West, and Central) of Ibadan Polytechnic: Citrobacter spp., 64%; Klebsiella spp., 7%; Enterobacter spp., Escherichia coli, and Serratia spp., 6% each; Proteus spp., 5%; and Salmonella spp. and Shigella spp., 3% each. The highest hetero trophic bacterial count of 9.3 × 103 CFU/ml was recorded at Ibadan Polytechnic North and South, while the least count (3.2 × 107 CFU/ml) was recorded at Ibadan Polytechnic Central. The highest enteric bacterial count of 1.3 × 103 CFU/ml was recorded in soymilk samples from Ibadan Polytechnic Central, while the least count of 1.7 × 107 CFU/ml was recorded in soymilk samples from Ibadan Polytechnic North. A total of 26% of the isolates showed resistance to cefpodoxime, while 88% of the isolates were susceptible to trimethoprim-sulfamethoxazole. Four of the MDR isolates possessed plasmid bands ranging from 6 to 1 with molecular weights from 2.7 to 17.2 kbp. Enterobacteriaceae such as isolates O14 (Klebsiella spp.) and B10 (E. coli) retained their resistance to antibiotics even after removal of plasmids, while isolates S13 (Citrobacter spp.) and O4 (Shigella spp.) were susceptible to some antibiotics after curing. Conclusively, soymilk sold in the sampled areas was highly con tami nated with Enterobacteriaceae, thereby indicating poor hygiene standards of soymilk production.

Abstract Background The timing of and risk factors for intestinal colonization with multidrug-resistant Enterobacteriaceae (MDRE) are still poorly understood in areas with high MDRE carriage. We determined the prevalence, timing, and risk factors associated with MDRE intestinal colonization among infants in southern Sri Lanka. Methods Women and their newborn children were enrolled within 48 h after delivery in southern Sri Lanka. Rectal swabs were collected from women and infants at enrollment and 4–6 weeks later. Enterobacteriaceae were isolated and identified as MDRE (positive for extended-spectrum β-lactamases or carbapenem resistant) using standard microbiologic procedures. We used exact methods (Fisher’s exact and Kruskal–Wallis tests) and multivariable logistic regression to identify sociodemographic and clinical features associated with MDRE intestinal colonization. Whole-genome sequencing was performed on selected MDRE isolates to identify phylogroups and antibiotic resistance-encoding genes were identified with NCBI’s AMRfinder tool. Results Overall, 199 post-partum women and 199 infants were enrolled; 148/199 (74.4%) women and 151/199 (75.9%) infants were reassessed later in the community. Twenty-four/199 (12.1%) women and 3/199 (1.5%) infants displayed intestinal colonization with MDRE at enrollment, while 26/148 (17.6%) women and 24/151 (15.9%) infants displayed intestinal colonization with MDRE at the reassessment. While there were no risk factors associated with infant colonization at enrollment, multivariable analysis indicated that risk factors for infant colonization at reassessment included mother colonized at enrollment (aOR = 3.62) or reassessment (aOR = 4.44), delivery by Cesarean section (aOR = 2.91), and low birth weight (aOR = 5.39). Of the 20 MDRE isolates from infants that were sequenced, multilocus sequence typing revealed that 6/20 (30%) were clustered on the same branch as MDRE isolates found in the respective mothers. All sequenced isolates for mothers (47) and infants (20) had at least one ESBL-producing gene. Genes encoding fosfomycin resistance were found in 33/47 (70%) of mothers’ isolates and 16/20 (80%) of infants’ isolates and genes encoding resistance to colistin were found in one (2%) mother’s isolate. Conclusions Our results suggest that a substantial proportion of infants undergo MDRE intestinal colonization within 6 weeks of birth, potentially due to postnatal rather than intranatal transmission.

Worldwide spread of Enterobacteriaceae resistant to colistin, a polypeptide antibacterial drug for last-resort treatment of carbapenemase-producing Enterobacteriaceae (CPE) infections, is concerning. This study aimed to elucidate colistin MICs and molecular characteristics of mcr-1 to mcr-9 of ESBL-producing Escherichia coli (ESBL-Ec) and CPE in Japan and clarify the genomic structure of strains harboring mcr genes (especially mcr-9). This study included 168 ESBL-Ec and 126 CPE strains isolated at Japanese medical facilities. Colistin susceptibility testing and multiplex PCR targeting mcr-1 to mcr-9 were performed for all strains with S1-nuclease pulsed-field gel electrophoresis, Southern blot hybridization, and whole-genome sequencing (WGS) with hybrid assembly performed for mcr gene-carrying strains. Two CPE strains showed a MIC ≥ 4 μg/ml in colistin susceptibility testing, with no known resistance mechanism detected. However, PCR conducted on all target strains detected three mcr-9-carrying strains showing colistin susceptibility. The blaCTX–M–62-positive E. coli THUN648 strain simultaneously carried blaCTX–M–62 and mcr-9 on a 275-kbp plasmid. Besides, blaIMP–6 + blaCTX–M–2-positive Klebsiella pneumoniae THUN262 and blaGES–24-positive Enterobacter kobei THUN627 had mcr-9 encoded on the chromosome. Only THUN627 encoded qseB/C, which is suggested to be a regulatory gene for mcr-9, downstream of mcr-9. However, this strain showed no increased expression of these genes in mRNA quantitative analysis under colistin exposure. Colistin MICs of ESBL-Ec and CPE in Japan were all below 2 μg/ml, which is below the epidemiological cutoff (ECOFF) value (https://eucast.org/) or clinical breakpoint (CB) (CLSI M100-S30) reported for colistin, indicating neither “microbiological” nor “clinical” resistance. Several colistin-susceptible Enterobacteriaceae carrying silent mcr-9 encoded on plasmids and chromosomes have already spread worldwide along with other antimicrobial resistance genes. However, the mechanism of colistin resistance by mcr-9 remains unclear.

Worldwide spread of Enterobacteriaceae resistant to colistin, a polypeptide antibacterial drug for last-resort treatment of carbapenemase-producing Enterobacteriaceae (CPE) infections, is concerning. This study aimed to elucidate colistin MICs and molecular characteristics of mcr-1 to mcr-9 of ESBL-producing Escherichia coli (ESBL-Ec) and CPE in Japan and clarify the genomic structure of strains harboring mcr genes (especially mcr-9). This study included 168 ESBL-Ec and 126 CPE strains isolated at Japanese medical facilities. Colistin susceptibility testing and multiplex PCR targeting mcr-1 to mcr-9 were performed for all strains with S1-nuclease pulsed-field gel electrophoresis, Southern blot hybridization, and whole-genome sequencing (WGS) with hybrid assembly performed for mcr gene-carrying strains. Two CPE strains showed a MIC ≥ 4 μg/ml in colistin susceptibility testing, with no known resistance mechanism detected. However, PCR conducted on all target strains detected three mcr-9 -carrying strains showing colistin susceptibility. The bla CTX–M–62 -positive E. coli THUN648 strain simultaneously carried bla CTX–M–62 and mcr-9 on a 275-kbp plasmid. Besides, bla IMP–6 + bla CTX–M–2 -positive Klebsiella pneumoniae THUN262 and bla GES–24 -positive Enterobacter kobei THUN627 had mcr-9 encoded on the chromosome. Only THUN627 encoded qseB/C , which is suggested to be a regulatory gene for mcr-9 , downstream of mcr-9. However, this strain showed no increased expression of these genes in mRNA quantitative analysis under colistin exposure. Colistin MICs of ESBL-Ec and CPE in Japan were all below 2 μg/ml, which is below the epidemiological cutoff (ECOFF) value (https://eucast.org/) or clinical breakpoint (CB) (CLSI M100-S30) reported for colistin, indicating neither "microbiological" nor "clinical" resistance. Several colistin-susceptible Enterobacteriaceae carrying silent mcr-9 encoded on plasmids and chromosomes have already spread worldwide along with other antimicrobial resistance genes. However, the mechanism of colistin resistance by mcr-9 remains unclear. [ABSTRACT FROM AUTHOR]

Background: The timing of and risk factors for intestinal colonization with multidrug-resistant Enterobacteriaceae (MDRE) are still poorly understood in areas with high MDRE carriage. We determined the prevalence, timing, and risk factors associated with MDRE intestinal colonization among infants in southern Sri Lanka. Methods: Women and their newborn children were enrolled within 48 h after delivery in southern Sri Lanka. Rectal swabs were collected from women and infants at enrollment and 4–6 weeks later. Enterobacteriaceae were isolated and identified as MDRE (positive for extended-spectrum β-lactamases or carbapenem resistant) using standard microbiologic procedures. We used exact methods (Fisher's exact and Kruskal–Wallis tests) and multivariable logistic regression to identify sociodemographic and clinical features associated with MDRE intestinal colonization. Whole-genome sequencing was performed on selected MDRE isolates to identify phylogroups and antibiotic resistance-encoding genes were identified with NCBI's AMRfinder tool. Results: Overall, 199 post-partum women and 199 infants were enrolled; 148/199 (74.4%) women and 151/199 (75.9%) infants were reassessed later in the community. Twenty-four/199 (12.1%) women and 3/199 (1.5%) infants displayed intestinal colonization with MDRE at enrollment, while 26/148 (17.6%) women and 24/151 (15.9%) infants displayed intestinal colonization with MDRE at the reassessment. While there were no risk factors associated with infant colonization at enrollment, multivariable analysis indicated that risk factors for infant colonization at reassessment included mother colonized at enrollment (aOR = 3.62) or reassessment (aOR = 4.44), delivery by Cesarean section (aOR = 2.91), and low birth weight (aOR = 5.39). Of the 20 MDRE isolates from infants that were sequenced, multilocus sequence typing revealed that 6/20 (30%) were clustered on the same branch as MDRE isolates found in the respective mothers. All sequenced isolates for mothers (47) and infants (20) had at least one ESBL-producing gene. Genes encoding fosfomycin resistance were found in 33/47 (70%) of mothers' isolates and 16/20 (80%) of infants' isolates and genes encoding resistance to colistin were found in one (2%) mother's isolate. Conclusions: Our results suggest that a substantial proportion of infants undergo MDRE intestinal colonization within 6 weeks of birth, potentially due to postnatal rather than intranatal transmission. [ABSTRACT FROM AUTHOR]

This study was conducted to determine the occurrence, antibiotic susceptibility pattern, and plasmid profile of multidrug-resistant (MDR) Enterobacteriaceae isolated from soymilk hawked in the Ibadan Polytechnic Community, Nigeria. Bacterial isolation and identification were performed using a culture-dependent method and biochemical characterization, respectively, while antibiotic susceptibility was tested using the disk diffusion method. Plasmid analysis and curing were performed using standard procedures. The results revealed the following occurrence rate of bacterial species in soymilk samples collected from all axes (South, North, East, West, and Central) of Ibadan Polytechnic: Citrobacter spp., 64%; Klebsiella spp., 7%; Enterobacter spp., Escherichia coli, and Serratia spp., 6% each; Proteus spp., 5%; and Salmonella spp. and Shigella spp., 3% each. The highest heterotrophic bacterial count of 9.3 × 10³ CFU/ml was recorded at Ibadan Polytechnic North and South, while the least count (3.2 × 107 CFU/ml) was recorded at Ibadan Polytechnic Central. The highest enteric bacterial count of 1.3 × 10³ CFU/ml was recorded in soymilk samples from Ibadan Polytechnic Central, while the least count of 1.7 × 107 CFU/ml was recorded in soymilk samples from Ibadan Polytechnic North. A total of 26% of the isolates showed resistance to cefpodoxime, while 88% of the isolates were susceptible to trimethoprim-sulfamethoxazole. Four of the MDR isolates possessed plasmid bands ranging from 6 to 1 with molecular weights from 2.7 to 17.2 kbp. Enterobacteriaceae such as isolates O14 (Klebsiella spp.) and B10 (E. coli) retained their resistance to antibiotics even after removal of plasmids, while isolates S13 (Citrobacter spp.) and O4 (Shigella spp.) were susceptible to some antibiotics after curing. Conclusively, soymilk sold in the sampled areas was highly contaminated with Enterobacteriaceae, thereby indicating poor hygiene standards of soymilk production. [ABSTRACT FROM AUTHOR]

Eravacycline (ERV) was used in 35 patients for various infections. The most common pathogen was Klebsiella pneumoniae, and 30-day survival was 74%. Absence of 30-day recurrence and resolution of signs and symptoms of infection were 91% and 57%, respectively. ERV was well-tolerated, with adverse events leading to drug discontinuation in one patient. [ABSTRACT FROM AUTHOR]

Eravacycline (ERV), formerly known as TP‐434, is a novel tetracycline (TET) antibiotic that exhibits in vitro activity against various gram‐positive, gram‐negative aerobic and anaerobic pathogens, including those exhibiting TET‐specific acquired resistance mechanisms. Similar to other TETs, it inhibits protein synthesis through binding to the 30S ribosomal subunit. Eravacycline was approved by the United States Food and Drug Administration (FDA) in August 2018 for the treatment of complicated intraabdominal infections (cIAIs) in adults following the Investigating Gram‐Negative Infections Treated with Eravacycline (IGNITE)1 and IGNITE4 phase III trials. In these two, double‐blind, multicenter clinical trials, ERV was proven noninferior in terms of clinical response in comparison to ertapenem and meropenem, respectively. Eravacycline was well tolerated with nausea, vomiting, and infusion site reactions being the most commonly reported adverse reactions. Clinicians now have ERV as a novel therapeutic option for the treatment of adults with intraabdominal infections, allergies to β‐lactam agents, Clostridioides difficile‐associated diarrhea, or if tolerability to other agents is a concern. [ABSTRACT FROM AUTHOR]

Abstract Background Infections with carbapenem-resistant Enterobacteriaceae (CRE) are increasingly being reported from patients in healthcare settings. They are associated with high patient morbidity, attributable mortality and hospital costs. Patients who are “at-risk” may be carriers of these multidrug-resistant Enterobacteriaceae (MDR-E). The purpose of this guidance is to raise awareness and identify the “at-risk” patient when admitted to a healthcare setting and to outline effective infection prevention and control measures to halt the entry and spread of CRE. Methods The guidance was created by a group of experts who were functioning independently of their organisations, during two meetings hosted by the European Centre for Disease Prevention and Control. A list of epidemiological risk factors placing patients “at-risk” for carriage with CRE was created by the experts. The conclusions of a systematic review on the prevention of spread of CRE, with the addition of expert opinion, were used to construct lists of core and supplemental infection prevention and control measures to be implemented for “at-risk” patients upon admission to healthcare settings. Results Individuals with the following profile are “at-risk” for carriage of CRE: a) a history of an overnight stay in a healthcare setting in the last 12 months, b) dialysis-dependent or cancer chemotherapy in the last 12 months, c) known previous carriage of CRE in the last 12 months and d) epidemiological linkage to a known carrier of a CRE. Core infection prevention and control measures that should be considered for all patients in healthcare settings were compiled. Preliminary supplemental measures to be implemented for “at-risk” patients on admission are: pre-emptive isolation, active screening for CRE, and contact precautions. Patients who are confirmed positive for CRE will need additional supplemental measures. Conclusions Strengthening the microbiological capacity, surveillance and reporting of new cases of CRE in healthcare settings and countries is necessary to monitor the epidemiological situation so that, if necessary, the implemented CRE prevention strategies can be refined in a timely manner. Creating a large communication network to exchange this information would be helpful to understand the extent of the CRE reservoir and to prevent infections in healthcare settings, by applying the principles outlined here. This guidance document offers suggestions for best practices, but is in no way prescriptive for all healthcare settings and all countries. Successful implementation will result if there is local commitment and accountability. The options for intervention can be adopted or adapted to local needs, depending on the availability of financial and structural resources.

Plazomicin is a novel aminoglycoside antibiotic that binds to the bacterial 30S ribosomal subunit, thus inhibiting protein synthesis in a concentration‐dependent manner. Plazomicin displays a broad spectrum of activity against aerobic gram‐negative bacteria including extended‐spectrum β‐lactamase–producing Enterobacteriaceae, carbapenem‐resistant Enterobacteriaceae, and organisms with aminoglycoside‐modifying enzymes. In a large phase III clinical trial, plazomicin was shown to be noninferior to meropenem in the treatment of complicated urinary tract infections (cUTIs) with respect to the coprimary efficacy end points of the microbiologically modified intent‐to‐treat composite cure rate at day 5 (plazomicin 88% [168/191 subjects] vs meropenem 91.4% [180/197]) and at the test‐of‐cure visit (plazomicin 81.7% [156/191] vs meropenem 70.1% [138/197]). In a small phase III clinical trial, plazomicin was shown to be effective in the treatment of infections caused by carbapenem‐resistant Enterobacteriaceae. It was associated with a lower all‐cause mortality or significant disease‐related complication rate (23.5% [4/17]) compared with colistin (50% [10/20]). The most common adverse reactions associated with plazomicin are decreased renal function, diarrhea, hypertension, headache, nausea, vomiting, and hypotension. As with other aminoglycosides, plazomicin may cause neuromuscular blockade, ototoxicity, and fetal harm in pregnant women. Due to limited efficacy and safety data, plazomicin is indicated for the treatment of cUTIs in adults with limited or no alternative treatment options, using a dosage regimen of 15 mg/kg intravenously every 24 hours for 4–7 days. Dosage reductions and therapeutic drug monitoring are warranted in patients with moderate or severe renal impairment. Plazomicin is not recommended in patients with severe renal impairment including those receiving renal replacement therapy. With the approval of plazomicin, clinicians now have an additional option for the treatment of adults with cUTIs, particularly those caused by multidrug‐resistant gram‐negative rods. [ABSTRACT FROM AUTHOR]

The microbiome has a strong impact on human health and disease and is, therefore, increasingly studied in a clinical context. Metaproteomics is also attracting considerable attention, and such data can be efficiently generated today owing to improvements in mass spectrometry-based proteomics. As we will discuss in this study, there are still major challenges notably in data analysis that need to be overcome. Here, we analyzed 212 fecal samples from 56 hospitalized acute leukemia patients with multidrug-resistant Enterobactericeae (MRE) gut colonization using metagenomics and metaproteomics. This is one of the largest clinical metaproteomic studies to date, and the first metaproteomic study addressing the gut microbiome in MRE colonized acute leukemia patients. Based on this substantial data set, we discuss major current limitations in clinical metaproteomic data analysis to provide guidance to researchers in the field. Notably, the results show that public metagenome databases are incomplete and that sample-specific metagenomes improve results. Furthermore, biological variation is tremendous which challenges clinical study designs and argues that longitudinal measurements of individual patients are a valuable future addition to the analysis of patient cohorts.

Background: Infections with carbapenem-resistant Enterobacteriaceae (CRE) are increasingly being reported from patients in healthcare settings. They are associated with high patient morbidity, attributable mortality and hospital costs. Patients who are "at-risk" may be carriers of these multidrug-resistant Enterobacteriaceae (MDR-E). The purpose of this guidance is to raise awareness and identify the "at-risk" patient when admitted to a healthcare setting and to outline effective infection prevention and control measures to halt the entry and spread of CRE. Methods: The guidance was created by a group of experts who were functioning independently of their organisations, during two meetings hosted by the European Centre for Disease Prevention and Control. A list of epidemiological risk factors placing patients "at-risk" for carriage with CRE was created by the experts. The conclusions of a systematic review on the prevention of spread of CRE, with the addition of expert opinion, were used to construct lists of core and supplemental infection prevention and control measures to be implemented for "at-risk" patients upon admission to healthcare settings. Results: Individuals with the following profile are "at-risk" for carriage of CRE: a) a history of an overnight stay in a healthcare setting in the last 12 months, b) dialysis-dependent or cancer chemotherapy in the last 12 months, c) known previous carriage of CRE in the last 12 months and d) epidemiological linkage to a known carrier of a CRE. Core infection prevention and control measures that should be considered for all patients in healthcare settings were compiled. Preliminary supplemental measures to be implemented for "at-risk" patients on admission are: preemptive isolation, active screening for CRE, and contact precautions. Patients who are confirmed positive for CRE will need additional supplemental measures. Conclusions: Strengthening the microbiological capacity, surveillance and reporting of new cases of CRE in healthcare settings and countries is necessary to monitor the epidemiological situation so that, if necessary, the implemented CRE prevention strategies can be refined in a timely manner. Creating a large communication network to exchange this information would be helpful to understand the extent of the CRE reservoir and to prevent infections in healthcare settings, by applying the principles outlined here. This guidance document offers suggestions for best practices, but is in no way prescriptive for all healthcare settings and all countries. Successful implementation will result if there is local commitment and accountability. The options for intervention can be adopted or adapted to local needs, depending on the availability of financial and structural resources. [ABSTRACT FROM AUTHOR]

The article offers information on the epidemiology of multidrug-resistant enterobacteriaceae. It mentions transmissibility of non–Escherichia coli Enterobacteriaceae in comparison with E. coli is higher. It also mentions rate of ESC-resistant Enterobacteriaceae acquisition in intensive care is higher to the prevalence of colonization at admission. It mentions impact of cessation of contact precautions for ESBL-producing E. coli have no consequences on the incidence of nosocomial transmissions.

There is no consensus on optimal screening procedures for multidrug-resistant Enterobacteriaceae ( MDRE) in intensive care units ( ICUs). Therefore, we assessed five strategies for the detection of extended-spectrum beta-lactamase ( ESBL) and high-level expressed AmpC cephalosporinase ( HL- CASE) producers. During a 3-month period, a rectal screening swab sample was collected daily from every ICU patient, from the first 24 h to the last day of ICU stay. Samples were plated on MDRE-selective media. Bacteria were identified using MALDI- TOF mass spectrometry and antibiograms were performed using disk diffusion. MDREs were isolated from 682/2348 (29.0%) screening samples collected from 93/269 (34.6%) patients. Incidences of patients with ESBL and HL- CASE producers were 17.8 and 19.3 per 100 admissions, respectively. In 48/93 patients, MDRE carriage was intermittent. Compared with systematic screening at admission, systematic screening at discharge did not significantly increase the rate of MDRE detection among the 93 patients (62% vs. 70%). In contrast, screening at admission and discharge, screening at admission and weekly thereafter, and screening at admission and weekly thereafter and at discharge significantly increased MDRE detection (77%, p 0.02; 76%, p 0.01; 86%, p <0.001, respectively). The difference in MDRE detection between these strategies relies essentially on the levels of detection of patients with HL- CASE producers. The most reasonable strategy would be to collect two samples, one at admission and one at discharge, which would detect 87.5% of the ESBL strains, 67.3% of the HL- CASE strains and 77.4% of all MDRE strains. This study should facilitate decision-making concerning the most suitable screening policy for MDRE detection in a given ICU setting. [ABSTRACT FROM AUTHOR]

This research aimed to investigate the microbial composition and diversity of antimicrobial resistance genes (ARGs) found in Chinese broiler and layer family poultry farms. We focused on the differences in resistance phenotypes and genotypes of multidrug-resistant Enterobacteriaceae (MDRE) isolated from the two farming environments and the existence and transmissibility of colistin resistance gene mcr-1 . Metagenomic analysis showed that Firmicutes and Bacteroides were the dominant bacteria in broiler and layer farms. Many aminoglycoside and tetracycline resistance genes were accumulated in these environments, and their absolute abundance was higher in broiler than in layer farms. A total of 526 MDRE were isolated with a similar distribution in both farms. The results of the K-B test showed that the resistance rate to seven antimicrobials including polymyxin B and meropenem in broiler poultry farms was significantly higher than that in layer poultry farms ( P ≤ 0.05). PCR screening results revealed that the detection rates of mcr-1 , aph(3')Ia , aad A2, bla oxa-1 , bla CTX-M , fos B, qnr D, sul1 , tet A, and cat A1 in broiler source MDRE were significantly higher than those in layers ( P ≤0.05). A chimeric plasmid p20432- mcr which carried the novel integron In1866 was isolated from broiler source MDRE. The high frequency of conjugation (10 -1 to 10 -3 ) and a wide range of hosts made p20432- mcr likely to play an essential role in the high detection rate of mcr-1 , aph(3')-Ia , and aad A2 in broiler farms. These findings will help optimize disinfection and improve antimicrobial-resistant bacteria surveillance programs in poultry farms, especially broilers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zong, Xu, Zheng, Zaeim, Wang, Han and Qu.)

The use of fosfomycin has been limited in therapeutics in recent years. Because it has shown good antibacterial activity in vitro and clinical efficacy in some domains, it has been proposed as an alternative to current antimicrobial agents, which are subject to increasing resistance. This paper reviews the main properties of fosfomycin and the latest publications concerning multidrugresistant Enterobacteriaceae infections. In uncomplicated urinary tract infections, a single oral dose was found to be safe and effective. In complicated urinary tract infections, the same results were observed with several doses. In both cases, by using fosfomycin to treat infections, the use of carbapenems could be reduced, leading to lower costs and better microbial ecology. In severe infections, combinations with intravenous fosfomycin need to be explored further because its future activity may depend on choosing a good partner drug. Because of the fast evolution of microbial resistance, more studies are urgently needed. [ABSTRACT FROM AUTHOR]

Background: Tigecycline, a new agent against multidrug-resistant (MDR) bacteria, is especially licensed for use in complicated skin and soft tissue and intra-abdominal infections. We aimed to study the recent in vitro activity of tigecycline against MDR Enterobacteriaceae skin and soft tissue isolates., Methods: Consecutive isolates (56 Escherichia coli , 48 Klebsiella pneumoniae ) were subjected to tigecycline susceptibility testing by Ezy MIC test and interpreted as per European Committee on Antimicrobial Susceptibility Testing., Results: The minimum inhibitory concentrations (MICs) of tigecycline ranged from 0.016 to 48 μg/mL, with MIC 50 0.19 μg/mL and MIC 90 1.0 μg/mL respectively. Seven (6.7%) isolates were resistant to tigecycline, all K. pneumoniae ., Conclusion: Tigecycline remains a viable therapeutic option against MDR isolates, with excellent in vitro activity against E. coli and promising activity against K. pneumoniae . However, the limited availability of alternate therapeutic armamentarium necessitates its use with extreme judiciousness along with continuous monitoring for the emergence and spread of resistance., Competing Interests: None to declare., (© 2021 The Authors. Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd.)

The microbiome has a strong impact on human health and disease and is, therefore, increasingly studied in a clinical context. Metaproteomics is also attracting considerable attention, and such data can be efficiently generated today owing to improvements in mass spectrometry-based proteomics. As we will discuss in this study, there are still major challenges notably in data analysis that need to be overcome. Here, we analyzed 212 fecal samples from 56 hospitalized acute leukemia patients with multidrug-resistant Enterobactericeae (MRE) gut colonization using metagenomics and metaproteomics. This is one of the largest clinical metaproteomic studies to date, and the first metaproteomic study addressing the gut microbiome in MRE colonized acute leukemia patients. Based on this substantial data set, we discuss major current limitations in clinical metaproteomic data analysis to provide guidance to researchers in the field. Notably, the results show that public metagenome databases are incomplete and that sample-specific metagenomes improve results. Furthermore, biological variation is tremendous which challenges clinical study designs and argues that longitudinal measurements of individual patients are a valuable future addition to the analysis of patient cohorts.

The risk of acquisition of multidrug-resistant Enterobacteriaceae (MRE) and of occurrence of diarrhea is high when traveling to tropical regions. The relationships between these phenomena and the composition of human gut microbiota have not yet been assessed. Here, we investigated the dynamics of changes of metabolically active microbiota by sequencing total RNA from fecal samples taken before and after travel to tropical regions. We included 43 subjects who could provide fecal samples before and after a travel to tropical regions. When found positive by culturing for any MRE after travel, the subjects sent an additional sample 1 month later. In all, 104 fecal samples were considered (43 before travel, 43 at return, 18 one month after travel). We extracted the whole RNA, performed retrotranscription and sequenced the cDNA (MiSeq 2x300bp). The reads were mapped to the reference operational taxonomic units (OTUs) and species/strains using the 16S Greengenes and 23S SILVA databases. We found that the occurrence of diarrhea during the travel was associated with a higher relative abundance of Prevotella copri before departure and after return. The composition of microbiota, before travel as well as at return, was not correlated with the acquisition of MRE. However, the clearance of MRE one month after return was linked to a specific pattern of bacterial species that was also found before and after return. In conclusion, we found specific OTUs associated to a higher risk of diarrhea during a stay in tropical regions and to a faster clearance of MRE after their acquisition.

The spread of multidrug-resistant Enterobacteriaceae related to the production of extended-spectrum β-lactamases (ESBL) and carbapenemases is a serious public health problem worldwide. Microbiological diagnosis and therapy of these infections are challenging and controversial. After the selection of clinically relevant questions, this document provides evidence-based recommendations for the use of microbiological techniques for the detection of ESBL- and carbapenemase-producing Enterobacteriaceae, and for antibiotic therapy for invasive infections caused by these organisms. The absence of randomized-controlled trials is noteworthy, thus recommendations are mainly based on observational studies, that have important methodological limitations, pharmacokinetic and pharmacodynamics models, and data from animal studies. Additionally, areas for future research were identified., (Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

The spread of multidrug-resistant Enterobacteriaceae related to the production of extended-spectrum β-lactamases and carbapenemases is a serious public health problem worldwide. Microbiological diagnosis and therapy of these infections are challenging and controversial. Clinically relevant questions were selected and the literature was reviewed for each of them. The information from the selected articles was extracted and recommendations were provided and graded according to the strength of the recommendations and quality of the evidence. The document was opened to comments from the members from the Spanish Society of Infectious Diseases and Clinical Microbiology, which were considered for inclusion in the final version. Evidence-based recommendations are provided for the use of microbiological techniques for the detection of extended-spectrum β-lactamases and carbapenemases in Enterobacteriaceae, and for antibiotic therapy for invasive/severe infections caused by these organisms. The absence of randomised controlled trials is noteworthy; thus, recommendations are mainly based on observational studies (that have important methodological limitations), pharmacokinetic and pharmacodynamics models, and data from animal studies. Additionally, areas for future research were identified., (Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)