Showing papers in "Journal of global antimicrobial resistance in 2020"
TL;DR: The clinical aspects of the novelBetacoronavirus disease (COVID-19) and its possible clinical presentations are summarised together with suggested therapeutic algorithms for patients who may require antimicrobial treatment, mainly associated with respiratory disease and few extrapulmonary signs.
Abstract: Objectives Following the public-health emergency of international concern (PHEIC) declared by the World Health Organization (WHO) on 30 January 2020 and the recent outbreak caused by 2019 novel coronavirus (2019-nCoV) [officially renamed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] in China and 29 other countries, we aimed to summarise the clinical aspects of the novelBetacoronavirus disease (COVID-19) and its possible clinical presentations together with suggested therapeutic algorithms for patients who may require antimicrobial treatment. Methods The currently available literature was reviewed for microbiologically confirmed infections by 2019-nCoV or COVID-19 at the time of writing (13 February 2020). A literature search was performed using the PubMed database and Cochrane Library. Search terms included ‘novel coronavirus’ or ‘2019-nCoV’ or ‘COVID-19’. Results Published cases occurred mostly in males (age range, 8–92 years). Cardiovascular, digestive and endocrine system diseases were commonly reported, except previous chronic pulmonary diseases [e.g. chronic obstructive pulmonary disease (COPD), asthma, bronchiectasis] that were surprisingly underreported. Fever was present in all of the case series available, flanked by cough, dyspnoea, myalgia and fatigue. Multiple bilateral lobular and subsegmental areas of consolidation or bilateral ground-glass opacities were the main reported radiological features of 2019-nCoV infection, at least in the early phases of the disease. Conclusion The new 2019-nCoV epidemic is mainly associated with respiratory disease and few extrapulmonary signs. However, there is a low rate of associated pre-existing respiratory co-morbidities.
246 citations
TL;DR: It is concluded that the use of antibiotics in food animal production constitutes a major contributing factor to the current antibiotic resistance crisis and they should only be used for treatment of sick animals based on prior diagnosis of disease.
Abstract: Antibiotics are frequently used in food animal production in developing countries to promote the well-being and growth of animals. This practice provides some economic benefits to producers and consumers at large. Nevertheless, this practice is also associated with a number of concerns. A major concern has been that repeatedly exposing these animals to small doses of antibiotics contributes significantly to antimicrobial resistance, since a good fraction of the antibiotics used are the same or surrogates of antibiotics used in human therapeutic practices. Studies over decades have shown an explicit relationship between antimicrobial use and antimicrobial resistance in veterinary science. Many antibiotics can be purchased over the counter in African countries, and antibiotic resistance is an important issue to address in this region. This review examines some of the risks and benefits associated with antibiotic use in food animals. We conclude that the use of antibiotics in food animal production constitutes a major contributing factor to the current antimicrobial resistance crisis and that antibiotics should only be used for the treatment of sick animals based on prior diagnosis of disease.
183 citations
TL;DR: In order to maintain its efficacy, CAZ-AVI should not be used for pathogens that are naturally resistant to it, and other effective antibacterial agents or CAZ -AVI in combination with other antib bacterial agents should be considered.
Abstract: Objective Ceftazidime–avibactam (CAZ-AVI) is a novel synthetic β-lactamase inhibitor combination. Although the combination has been available clinically for only a few years, cases of resistance to CAZ-AVI have already been reported. Methods In the present review, we summarize the distribution of CAZ-AVI-resistant strains and the possible resistance mechanisms. Results There are no significant differences in CAZ-AVI resistance rates across different regions. CAZ-AVI maintains good activity against Gram-negative bacteria, especially Enterobacteriaceae. Pseudomonas aeruginosa is less susceptible to CAZ-AVI compared with Enterobacteriaceae, with a resistance rate ranging from 2.9 to 18%. The resistance to CAZ-AVI exceeds 50% in Acinetobacter baumannii. A higher resistance rate to CAZ-AVI is associated with carbapenem resistance. Moreover, β-lactamase-related amino acid substitutions are the main mechanisms that lead to CAZ-AVI resistance. Membrane protein amino acid substitutions and efflux pumps also play important roles in CAZ-AVI resistance. Conclusions To maintain its efficacy, CAZ-AVI should not be used for pathogens that are naturally resistant to it. For CAZ-AVI-resistant strains, other effective antibacterial agents or CAZ-AVI in combination with other antibacterial agents should be considered.
109 citations
TL;DR: The current research represents first in vivo evidences for effective phage therapy against K. pneumoniae infection by using intranasal route and the loss of severity of lesions suggested overall beneficial effects of phage Therapy using BPA43 in the pneumonic mouse model.
Abstract: Objectives Klebsiella pneumoniae is an important emerging pathogen of humans and animals leading to serious clinical consequences. Increased antibiotic use has promoted the emergence of carbapenem-resistant and extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae strains. Recently, phage therapy has gained momentum as a possible alternative against emerging antimicrobial resistance. This study was performed to assess the therapeutic effects of a novel lytic phage (VTCCBPA43) in a pneumonic mouse model in order to explore the efficacy of phage therapy against virulent K. pneumoniae infection. Methods The tailed phage VTCCBPA43 was assessed for its growth kinetics, in vitro host range, and temperature and pH sensitivity. Protein constituents were analysed by SDS-PAGE and nLC-MS/MS. Therapeutic efficacy was observed 2 h post-challenge with virulent K. pneumoniae in a BALB/c mouse model. Results Phage VTCCBPA43 was found to be highly temperature-tolerant (up to 80 °C). It was most active at pH 5, had a burst size of 172 PFU/mL and exhibited a narrow host range. It was identified as a KP36-like phage by shotgun proteomics. Following intranasal application of a single dose (2 × 109 PFU/mouse) post-challenge with virulent K. pneumoniae, the presence of biologically active phage in vivo and a significant reduction in the lung bacterial load at all time points was observed. A reduction in lesion severity suggested overall beneficial effects of VTCCBPA43 phage therapy in the pneumonic mouse model. Conclusion This research represents the first in vivo evidence of effective phage therapy against K. pneumoniae infection by the intranasal route.
80 citations
TL;DR: The paucity of data on implementation of ASPs in African countries shows the continent is faced with challenges which impact on effective implementation of these programmes, but the successes reported in the included studies show that other African countries can implement these programmes.
Abstract: Objective Antimicrobial stewardship is one of the strategic objectives of the WHO global action plan on antimicrobial resistance. This paper sought to review the extent of implementation of antimicrobial stewardship programmes (ASPs) in African countries and the reported outcomes. Methods We searched five electronic databases, including PubMed, Scopus, Cochrane library, African Journal Online, CINAHL and Google scholar for papers published between 1990 and March 2019. We combined the names of countries in the five regions of Africa with antimicrobial stewardship terms. Studies of any design, employing any stewardship strategies were included. The quality of included studies was assessed using the National Heart, Lung and Blood Institute (NHLBI) quality assessment tool for before and after studies. Results Of 1752 titles identified, 13 studies met the criteria for inclusion. Seven of the studies were conducted in South Africa, three in Kenya and one each in Sudan, Tanzania and Egypt. Eleven studies were of high quality with low risk of bias. The included studies mainly assessed the outcome using process measures and these were associated with improved compliance with antibiotic guidelines, appropriateness of prescribing, reduction in antibiotic use and cost savings. Decrease in rate of surgical site infections and nonsignificant change in mortality and 30-day readmission rate were reported in two studies respectively. Conclusion Findings of this review show the paucity of data on implementation of ASPs in African countries. Although the continent is faced with challenges which impact on effective implementation of ASPs, the successes reported in the included studies show that other African countries can implement these programmes.
79 citations
TL;DR: In this article, the authors showed that daily vitamin D supplementation with moderate doses is safe and cheap and even a small decrease in COVID-19 infections would easily justify this intervention.
Abstract: • Vitamin D deficiency is very common. • Randomised controlled trials showed that vitamin D decreases acute respiratory infections (ARIs). • Vitamin D deficiency is an easily modifiable factor of ARIs. • Daily vitamin D supplementation with moderate doses is safe and cheap. • Even a small decrease in COVID-19 infections would easily justify this intervention.
71 citations
TL;DR: High dose vitamin C therapy could dramatically reduce the need for high doses of corticosteroids, antibacterial and anti-viral drugs that may be immunosuppressive, adrenal depressive, and toxic, complicating the disease course.
Abstract: Coronaviruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses increase oxidative stress in the body leading to cellular and tissue damage. To combat this, administration of high-dose vitamin C (ascorbic acid or ascorbate), in addition to standard conventional supportive treatments, has been shown to be a safe and effective therapy for severe cases of respiratory viral infection. Morbidity, mortality, infectiveness and spread of infectious diseases are dependent on the host-pathogen relationship. Given the lack of effective and safe antiviral drugs for coronaviruses, there should be more attention in supporting host immune defence, cytoprotection and immunoregulation. Implementation of high-dose vitamin C therapy could dramatically reduce the need for high doses of corticosteroids, antibacterials and antiviral drugs that may be immunosuppressive, adrenal depressive and toxic, complicating the disease course. In order to effectively fight the novel SARS-CoV-2 virus, medical professionals should explore readily available pharmaceutical and nutritional therapeutic agents with proven antioxidant, anti-inflammatory and immunosupportive properties. Supplemental vitamin C may also provide additional benefits for the prevention of viral infections, shorten the disease course and lessen complications of the disease.
68 citations
TL;DR: This review traces the prevalence of ST11 CRKP in China Antimicrobial Surveillance Network (CHINET), the key drug resistance mechanisms, and virulence evolution, and demonstrates a very close linkage among IncF plasmids, NTEKPC, and ST11 Klebsiella pneumoniae in China.
Abstract: Sequence type 11 (ST11) carbapenem-resistant Klebsiella pneumoniae (CRKP) has become the dominant clone in China. In this review, we trace the prevalence of ST11 CRKP in the China Antimicrobial Surveillance Network (CHINET), the key antimicrobial resistance mechanisms and virulence evolution. The recent emergence of ST11 carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) strains in China due to the acquisition of a pLVPK-like virulence plasmid, which may cause severe infections in relatively healthy individuals that are difficult to treat with current antibiotics, has attracted worldwide attention. There is a very close linkage among IncF plasmids, NTEKPC and ST11 K. pneumoniae in China. Hybrid conjugative virulence plasmids are demonstrated to readily convert a ST11 CRKP strain to a CR-hvKP strain via conjugation. Understanding the molecular evolutionary mechanisms of resistance and virulence-bearing plasmids as well as the prevalence of ST11 CRKP in China allows improved tracking and control of such organisms.
67 citations
TL;DR: Overall the results show a global increase in the prevalence of H LMuRSA and HLMuRMRSA among clinical S. aureus isolates over time, however, there was only a significant increase inThe prevalence of MuR MRSA compared to the other categories of strains especially MuRSA.
Abstract: Objectives Staphylococcus aureus is one of the most common pathogens causing nosocomial and community-acquired infections associated with high morbidity and mortality. Mupirocin has been increasingly used for treatment of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) infections. The aim of this study was to determine the prevalence of mupirocin-resistant S. aureus (MuRSA), mupirocin-resistant MRSA (MuRMRSA), high-level MuRSA (HLMuRSA) and high-level MuRMRSA (HLMuRMRSA) worldwide. Methods Online databases including Medline, Embase and Web of Science were searched (2000–2018) to identify studies addressing the prevalence of MuRSA, MuRMRSA, HLMuRSA and HLMuRMRSA. STATA v. software was used to interpret the data. Results Of the 2243 records identified from the databases, 30 and 63 studies fulfilled the eligibility criteria for MuRSA and MuRMRSA, respectively. Finally, 27 and 60 studies were included separately for HLMuRSA and HLMuRMRSA, respectively. The analyses revealed pooled and averaged prevalences of MuRSA, MuRMRSA, HLMuRSA and HLMuRMRSA of 7.6% [95% confidence interval (CI) 6.2–9.0%], 13.8% (95% CI 12.0–15.6%), 8.5% (95% CI 6.3–10.7%) and 8.1% (95% CI 6.8–9.4%), respectively. Conclusion Overall, these results show a global increase in the prevalence of HLMuRSA and HLMuRMRSA among clinical S. aureus isolates over time. However, there was only a significant increase in the prevalence of MuRMRSA compared with the other categories, especially MuRSA. Since mupirocin remains the most effective antibiotic for MSSA and MRSA decolonisation both in patients and healthcare personnel, a reduction of its effectiveness presents a risk for invasive infection. Monitoring of mupirocin resistance development remains critical.
66 citations
TL;DR: The results suggested that the presence of only NDM or PER would not lead to non-susceptibility to CFDC and that multiple factors would be related with CFDC resistance.
Abstract: Objective To investigate possible mechanistic factors to explain cefiderocol (CFDC) non-susceptibility, we characterized 38 clinical isolates with a CFDC minimum inhibitory concentration (MIC) of >4 μg/mL from a multi-national surveillance study. Methods The MIC measurement in the presence of β-lactamase inhibitors and whole genome sequencing were performed. Results The MIC decrease of CFDC by β-lactamase inhibitors was observed against all of the test isolates. Among the 38 isolates, NDM and PER genes were observed in 5 and 25 isolates, respectively. No other β-lactamases responsible for high MIC were identified in the other eight isolates. The MIC of CDFC against Escherichia coli isogenic strains introduced with NDM and PER β-lactamase increased by ≥16-fold, suggesting the contribution of NDM and PER to the non-susceptibility to CFDC. Against NDM producers, a ≥8-fold MIC increase was observed only when both serine- and metallo-type β-lactamase inhibitors were added. In addition, many of the PER or NDM producers remained susceptible to CFDC. These results suggested that the presence of only NDM or PER would not lead to non-susceptibility to CFDC and that multiple factors would be related to CFDC resistance. Conclusion Multiple factors including NDM and PER could be related to reduced susceptibility to CFDC.
64 citations
TL;DR: COVID-19 patients have an exaggerated risk of acquiring BSI during ICU stay, which is higher than that reported in European ICUs in the pre-CO VID-19 period.
Abstract: • COVID-19 patients have an exaggerated risk of acquiring BSI during ICU stay. • The incidence of ICU-acquired BSI in COVID-19 patients is higher than that reported in European ICUs in the pre-COVID-19 period. • The commonest aetiological agents of BSI were intestinal commensals. • A high rate of acquisition of VRE colonisation was observed.
TL;DR: A high rate of agreement with the proposed actions to contrast AMR was documented; in particular, percentages of agreement were 75% of respondents who agreed to be part of an active surveillance system or AMS programs.
Abstract: Objectives Antimicrobial resistance (AMR) is one of the major health issues worldwide. Clinicians should play a central role to fight AMR, and medical training is a pivotal issue to combat it; therefore, assessing levels of knowledge, attitudes and practices among young doctors is essential for future antimicrobial stewardship (AMS) programmes. Methods A nationwide, cross-sectional, multicentre survey was conducted in Italy. A descriptive analysis of knowledge and attitudes was performed, along with a univariate and multivariate analysis of their determinants. Results Overall, 1179 young doctors accessed the survey and 1055 (89.5%) completed all sections. Regarding the knowledge section of the questionnaire, almost all participants declared to know the different species of bacteria proposed, however the percentage of participants who correctly responded to clinical quizzes was 23% for the question on vancomycin-resistant enterococci (VRE), 42% on carbapenem-resistant Enterobacteriaceae (CRE), 32% on extended-spectrum β-lactamase-producing enterobacteria (ESBL) and 27% on methicillin-resistantStaphylococcus aureus (MRSA). Similarly, 81% of participants disagreed in stating that AMR was adequately addressed during their medical training and 71% disagreed that they received the right example from their tutors. Finally, a high rate of agreement with the proposed actions to combat AMR was documented; in particular, the percentage agreement was 76% for respondents who agreed to be part of an active surveillance system or AMS programme. Conclusions Tackling AMR should be a priority for politicians and for all health workers. Inclusion of competencies in antibiotic use in all specialty curricula is urgently needed.
TL;DR: Occurrence of mcr-9 was common among clinical ESBL-producing Enterobacteriaceae isolates from horses in Sweden, and was linked to the ESbl-encoding gene blaSHV-12, and plasmid replicon types IncHI2 and Inc HI2A.
Abstract: Objectives The aim of this study was to investigate the occurrence of the newly described transferable colistin resistance gene mcr-9 in extended-spectrum β-lactamase (ESBL)-producing clinical Enterobacteriaceae isolates from horses in Sweden. Methods A total of 56 whole-genome sequenced ESBL-producing Enterobacteriaceae isolates from horses were subjected to in silico detection of antimicrobial resistance genes and identification of plasmid replicons types. The colistin minimum inhibitory concentration (MIC) for mcr-positive isolates was determined by broth microdilution. Relatedness between Enterobacteriaceae carrying mcr genes was determined by multilocus sequence typing (MLST) and core genome MLST. Results Thirty ESBL-producing Enterobacteriaceae isolates from horses were positive for the colistin resistance gene mcr-9. These isolates included Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca and Citrobacter freundii and belonged to diverse MLST sequence types within each species. Two of the mcr-9-containing isolates originated from the same horse. All mcr-9-positive isolates had colistin MICs below or equal to the EUCAST epidemiological cut-off value of 2 mg/L and were negative for the two potential regulatory genes qseB-like and qseC-like for mcr-9. Except for one isolate carrying only blaTEM-1B, all of the isolates carried blaSHV-12 and blaTEM-1B, and were all considered multidrug-resistant as they harboured genes encoding resistance to aminoglycosides, chloramphenicol, fosfomycin, macrolides, quinolones, sulfonamides, trimethoprim and tetracyclines. Plasmid replicon types IncHI2 and IncHI2A were detected in all mcr-9-positive isolates. Conclusion The occurrence of mcr-9 was common among clinical ESBL-producing Enterobacteriaceae isolates from horses in Sweden and was linked to the ESBL-encoding gene blaSHV-12 and plasmid replicon types IncHI2 and IncHI2A.
TL;DR: A "one health approach" is needed to monitor antibiotic resistance, with reference to the WHO Global Action Plan, and the results showed heterogeneous surveillance systems.
Abstract: Objectives Epidemiological surveillance is one critical approach to estimate and fight the burden of antibiotic resistance (AR). Here we summarise the characteristics of surveillance systems devoted to the surveillance of AR worldwide and published in the literature. Methods We performed a systematic review of the literature available on PubMed from January 2007 to July 2019 (12.5 years). The keywords (‘surveillance system’ OR ‘laboratory-based surveillance’ OR ‘syndromic surveillance’ OR ‘sentinel surveillance’ OR ‘integrated surveillance’ OR ‘population-based surveillance’) AND (‘antibiotic resistance’ OR ‘antimicrobial resistance’) were used. This research was completed with AR monitoring systems available on websites. Results We identified 71 AR surveillance systems described by 90 publications from 35 countries, including 64 (90.1%) national and 7 (9.9%) multinational surveillance systems. Two regions accounted for ∼72% of systems: European region (37; 52.1%) and Region of the Americas (14; 19.7%). Fifty-three focused on AR surveillance in humans, 12 studied both humans and animals, and 6 focused only on animals. The two most common bacterial species reported were Staphylococcus aureus (42; 59.2%) and Escherichia coli (39; 54.9%). Of the 71 AR surveillance systems, 20 (28.2%) used prevalence as an indicator, 3 (4.2%) used incidence and 7 (9.9%) used both. Methicillin-resistant S. aureus (MRSA), vancomycin-resistant Enterococcus spp., S. aureus and Streptococcus pneumoniae, penicillin-resistant S. pneumoniae, and extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant E. coli and Klebsiella pneumoniae were monitored. Conclusions Our results showed heterogeneous surveillance systems. A ‘One Health’ approach is needed to monitor AR, with reference to the WHO Global Action Plan.
TL;DR: Recombinant LysSS demonstrated that LysSS can be a novel and promising antimicrobial agent against MRSA and MDR Gram-negative bacteria including A. baumannii and P. aeruginosa.
Abstract: Objectives Multidrug-resistant (MDR) bacteria are a major public-health concern. Bacteriophage endolysins (lysins) can be used as novel antimicrobial agents against bacterial infections. In this study, a novel endolysin (LysSS) containing a lysozyme-like domain was evaluated for its antibacterial activity against various species of bacteria. Methods The LysSS-encoding gene was analyzed and cloned and the LysSS recombinant protein was expressed and purified. Purified LysSS was used to determine its antimicrobial activity against various bacterial species in vitro and to measure its protection rate against Acinetobacter baumannii systemic infection in an in vivo murine model. Results Recombinant LysSS showed activity against MDR A. baumannii, MDR Escherichia coli, MDR Klebsiella pneumoniae, MDR Pseudomonas aeruginosa and Salmonella sp. without pre-treatment with an outer membrane permeabiliser. Moreover, LysSS inhibited the growth of methicillin-resistant Staphylococcus aureus (MRSA). The minimum inhibitory concentration (MIC) of LysSS against 16 MDR A. baumannii strains ranged from 0.063–0.25 mg/mL. LysSS had no cytotoxic effect on A549 human lung cells below 250 μg/mL. In an animal model, mice infected with A. baumannii were protected (40% survival rate with 125 μg LysSS) by intraperitoneal injection of LysSS. Conclusion The current results demonstrate that LysSS may be a novel and promising antimicrobial agent against MRSA and MDR Gram-negative bacteria, including A. baumannii and P. aeruginosa.
TL;DR: This review describes two classes of antimicrobials, namely antimicrobial nanoparticles and antimicrobial peptides, and applications in the food industry and medical applications are discussed, and the directions for future research are highlighted.
Abstract: Biofilms can be produced by multiple species or by a single strain of bacteria. The biofilm state enhances the resistance of the resident microorganisms to antimicrobial agents by producing extracellular polymeric substances. Typically, antibiotics are used to stop the growth of bacteria, but emerging resistance has limited their effectiveness. Bacteria in biofilms are less susceptible to antibiotics compared with their free-floating state, as biofilms impair antibiotic penetration. To obviate this challenge, non-antibiotic antimicrobial agents are needed. This review describes two classes of these agents, namely antimicrobial nanoparticles and antimicrobial peptides. Applications of these antimicrobials in the food industry and medical applications are discussed, and the directions for future research are highlighted.
TL;DR: General Intensive Care Unit, University Hospital Southampton NHS Foundation Trust, Southampton, Tremona Road, Southampton; and International Society of Antimicrobial Chemotherapy, Chair of Rapid Diagnostics and Biomarker Working Group.
Abstract: General Intensive Care Unit, University Hospital Southampton NHS Foundation Trust, Southampton, Tremona Road, Southampton, UK b Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK Department of Biochemistry University Hospital Southampton NHS Foundation Trust, University of Southampton School of Medicine, Southampton, UK Microbiology Innovation and Research Unit (MIRU), Department of Microbiology, University Hospitals Southampton NHS Foundation Trust, and University of Southampton School of Medicine, Southampton, UK e International Society of Antimicrobial Chemotherapy (ISAC), Chair of Rapid Diagnostics and Biomarker Working Group
TL;DR: High prescribing rates for amikacin and penicillins and prolonged intravenous treatments in hospitalised children with febrile and afebrile urinary tract infections are observed, whilst E.coli appeared to be highly resistant to ampicillin, whilst 3rd generation cephalosporins exhibited higher in vitro efficacy.
Abstract: Objectives The aim of this study was to describe antibiotic prescribing patterns and antimicrobial resistance rates in hospitalised children with febrile and afebrile urinary tract infections (UTIs). Methods Antibiotic prescriptions and antibiograms for neonates, infants and older children with UTI admitted to a general district hospital in Central Greece were evaluated. Data covering a 5-year period were collected retrospectively from the Paediatric Department’s Electronic Clinical Archive. Patients were included based on clinical and microbiological criteria. Antimicrobial susceptibility was determined by the Kirby–Bauer disk diffusion method. Results A total of 230 patients were included in the study. Among 459 prescriptions identified, amikacin (31.2%) was the most common antibiotic prescribed in this population, followed by amoxicillin/clavulanic acid (17.4%) and ampicillin (13.5%). Children received prolonged intravenous (i.v.) treatments for febrile (mean ± S.D., 5.4 ± 1.45 days) and afebrile UTIs (mean ± S.D., 4.4 ± 1.64 days). A total of 236 pathogens were isolated. The main causative organism was Escherichia coli (79.2%) with high reported resistance rates to ampicillin (42.0%), trimethoprim/sulfamethoxazole (26.5%) and amoxicillin/clavulanic acid (12.2%); lower resistance rates were identified for third-generation cephalosporins (1.7%), nitrofurantoin (2.3%), ciprofloxacin (1.4%) and amikacin (0.9%). Klebsiella spp. isolates were highly resistant to cefaclor (27.3%). Conclusion High prescribing rates for amikacin and penicillins (± β-lactamase inhibitors) and prolonged i.v. treatments were observed. Escherichia coli was highly resistant to ampicillin, whilst third-generation cephalosporins exhibited greater in vitro efficacy. Establishment of antimicrobial stewardship programmes and regular monitoring of antimicrobial resistance could help to minimise inappropriate prescribing for UTIs.
TL;DR: The results show that farms are an important reservoir of colistin-resistant E.coli, added to other additional genes, such as blaESBL, posing a worrying threat to human health.
Abstract: Objectives Colistin resistance has emerged worldwide, threatening the efficacy of colistin treatment of Gram-negative bacterial infections. Farms have been recognised as an important reservoir of genes conferring resistance to colistin. This study aimed to isolate and characterise colistin-resistant bacteria in farmlands located in the region of Oran, northwest Algeria. Methods Forty environmental samples were collected between May 2016 and March 2018 at eight agricultural sites in the Oran region. Results From the 40 samples, 103 colistin-resistant isolates were isolated from agricultural soil (n = 52), irrigation water (n = 31) and manure (n = 20). Eight isolates were identified as Escherichia coli, including six and two isolates carrying the mcr-1 and mcr-3 gene, respectively. All eight E. coli isolates were non-susceptible to amoxicillin, amoxicillin/clavulanic acid, ticarcillin, nalidixic acid, ciprofloxacin, gentamicin, trimethoprim/sulfamethoxazole and rifamycin; two were also non-susceptible to cefotaxime, cefepime and aztreonam and carried the blaTEM-12 gene in addition to mcr-1. The six mcr-1-carrying E. coli isolates (MIC ≥ 2 μg/mL) belonged to three sequences types, including ST10 (n = 3), ST405 (n = 2) and ST345 (n = 1), whereas the two mcr-3-carrying isolates were assigned to ST155. The conjugation assay was positive only for two mcr-1-positive isolates. Conclusion These results show that farms are an important reservoir of colistin-resistant E. coli as well as other antimicrobial resistance genes such as ESBL genes. Transfer of manure from animals to soil and irrigation water might be disseminating a mix of multiple resistances, posing a worrying threat to human health.
TL;DR: This real-time PCR assay allowed the first description of a clinical K. pneumoniae strain harboring the mcr-8 gene in Algeria and was highly sensitive on a 10-fold dilution serie from a calibrated inoculum with a limit of detection at 55 CFU/mL.
Abstract: Objectives We aimed to develop here a specific real-time PCR assay with TaqMan® probe to detect efficiently bacterial strains harboring the new plasmid mediated-colistin resistance mcr-8 gene. Methods Specific primers and probe for mcr-8 gene were designed from sequences alignment of all mcr genes variants. Specificity of the designed primers and probe were first checked par BlastN analysis and by in silico PCR. The analytical sensitivity and specificity tests were performed in vitro on a panel of 290 genomic DNA of Gram-negative bacteria and 250 metagenomic DNA from human stool samples. Whole genome sequencing (WGS) was performed here using MiSeq technology. Results Designed primers and probe were 100% specific tomcr-8 gene by BlastN and in silico PCR analysis. Real-time PCR screening of a collection of clinical isolates resulted to one positive Klebsiella pneumoniae isolate (KP95). WGS confirmed that this isolate harbored the mcr-8 gene and other resistance genes such as blaOXA-48, blaCTX-M-15 β-lactamases. Our real-time PCR was highly sensitive on a 10-fold dilution serie from a calibrated inoculum at 108 CFU/mL with a limit of detection at 55 CFU/mL. Conclusion To the best of our knowledge, we propose here, the first real-time PCR assay targeting mcr-8 gene with high specificity and sensitivity, able to detect mcr-8 gene in less than 2 h from any DNA sample. This real-time PCR assay allowed the first description of a clinical K. pneumoniae strain harboring the mcr-8 gene in Algeria.
TL;DR: It is reported that 7 ICU patients with COVID-19 related ARDS, who developed positive rectal swab and invasive infections due to CP-Kp, must remain high, especially in critically ill setting.
Abstract: Here we report on seven intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS) who developed positive rectal swabs and invasive infections due to carbapenemase-producing Klebsiella pneumoniae (CP-Kp). Notwithstanding the infection prevention measures introduced during the COVID-19 pandemic and changes in the hospitalised population, attention to CP-Kp infections must remain high, especially in the critically ill setting.
TL;DR: The results showed that age, gender and diabetes were not associated with CRKP infection, and immunosuppression, ICU admission, antibiotics exposure and surgery, mechanical ventilation, central venous catheterization, indwelling catheter and nasogastric catheter intubation are risk factors for CRkP infection.
Abstract: Objectives Rates of nosocomial infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) have increased. A meta-analysis was conducted to explore risk factors for CRKP infection in order to provide a theoretical basis for reducing the CRKP infection rate and actively preventing CRKP infection. Methods Online databases, including PubMed, EMBASE, OVID, ClinicalKey, CNKI, CBM, Wanfang Database and CHKD, were searched from inception up to 31 October 2018 for articles regarding risk factors for CRKP infection. Relevant articles were retrieved, supplemented by retrospective and manual search literature. RevMan 5.3 software was used for statistical analysis. Results A total of 30 articles comprising 5075 cases were included in the study, of which 24 were in English and 6 were in Chinese. The results showed that age, sex and diabetes mellitus were not associated with CRKP infection. The odds ratio (95% confidence interval) of risk factors for CRKP infection were as follows: immunosuppression, 1.47 (1.14–1.90); ICU admission, 3.25 (2.36–4.47); antibiotic exposure, 2.53 (1.56–4.11); carbapenem exposure, 3.99 (2.86–5.56); quinolone exposure, 1.75 (1.38–2.22); glycopeptide exposure, 3.08 (1.93–4.91); β‑lactam/β‑lactamase inhibitor (BL/BLI) exposure, 2.28 (1.37–3.80); surgery, 1.59 (1.08–2.34); mechanical ventilation, 2.91 (1.96–4.31); central venous catheterisation, 2.93 (2.00–4.28); indwelling catheter, 2.62 (1.65–4.17); and nasogastric intubation, 2.38 (1.22–4.62). Conclusion Immunosuppression, ICU admission, antibiotic exposure (including carbapenems, quinolones, glycopeptides and BL/BLIs), surgery, mechanical ventilation, central venous catheterisation, indwelling catheter and nasogastric intubation were identified as risk factors for CRKP infection and should to be considered in clinical practice.
TL;DR: Findings show that moxifloxacin may be a promising antimicrobial against P. gingivalis, T. forsythia, and A. actinomycetemcomitans for the treatment of periodontitis, however, amoxicillin, azithromycin, and metronidazole were less effective.
Abstract: Objectives Administration of systemic antimicrobials as an adjunct to mechanical treatment of periodontitis and sites with adverse clinical results leads to improved outcomes. This study aimed to assess the antimicrobial susceptibility of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Tannerella forsythia isolated from periodontitis patients to amoxicillin, metronidazole, azithromycin and moxifloxacin. Methods A total of 76 patients diagnosed with generalised periodontitis were included in the study. Subgingival samples were processed by culture. Etest was used to determine susceptibility to amoxicillin, metronidazole, azithromycin and moxifloxacin. Results A total of 141 isolates from 76 patients were evaluated, including 61 P. gingivalis, 43 T. forsythia and 37 A. actinomycetemcomitans. Etest results showed complete susceptibility of A. actinomycetemcomitans, P. gingivalis and T. forsythia to moxifloxacin. However, the isolates presented reduced susceptibility to the other antimicrobial agents investigated. Of the A. actinomycetemcomitans isolates, 70.3%, 40.5% and 89.2% were resistant to amoxicillin, azithromycin and metronidazole, respectively. The P. gingivalis samples showed relatively similar rates of resistance to amoxicillin (24.6%), azithromycin (21.3%) and metronidazole (24.6%). Similarly, 25.6%, 21.0% and 25.6% of the T. forsythia isolates were resistant to amoxicillin, azithromycin, and metronidazole, respectively. Conclusion These findings show that moxifloxacin may be a promising antimicrobial agent against P. gingivalis, T. forsythia and A. actinomycetemcomitans for the treatment of periodontitis. However, amoxicillin, azithromycin and metronidazole were less effective, especially against A. actinomycetemcomitans in vitro.
TL;DR: It is demonstrated that HMRGs were widely present in E. coli and Salmonella isolated from chicken farm and retail meats, and the association between H MRGs with DRGs and ARGs may lead to the co-resistance of heavy metals and other antimicrobials.
Abstract: Objectives With the wide use of heavy metals as feed additives in animal production, little attention has been paid to heavy metal resistance in pathogenic bacteria. This study was performed to investigate the presence of heavy metal resistance genes (HMRGs) in Escherichia coli and Salmonella isolates and its correlation with disinfectant resistance genes (DRGs) and antibiotic resistance genes (ARGs). Methods HMRGs of 178 E. coli and 294 Salmonella isolated from chicken broiler farms and retail meat were detected by PCR. Minimum inhibitory concentrations (MICs) of heavy metals were determined by the broth microdilution method. The complete genome of E. coli E308, which had indications of multidrug resistance, was recovered and assembled using third-generation sequencing. Results The frequency of different HMRGs in E. coli and Salmonella ranged from 0.60–77.0% and 0.30–87.1%, respectively. MICs of heavy metals for E. coli and Salmonella ranged widely from ≤12.5 mg/L to 1600 mg/L. Moreover, HMRGs (zntA, arsB, merA, pcoR, pcoA, pcoC and chrA) were found to be significantly associated with one or more DRGs [sugE(c), emrE, mdfA, ydgE/ydgF, qacF, sugE(p) and qacEΔ1] and ARGs (sul1, sul2, sul3, tetA, tetB, tetC, blaTEM, blaSHV and blaCTX) (P Conclusion This study demonstrated that HMRGs are widely present in E. coli and Salmonella isolated from chicken farms and retail meat. The association between HMRGs with DRGs and ARGs may lead to co-resistance to heavy metals and other antimicrobial agents.
TL;DR: Imipenem-relebactam demonstrated potent in vitro activity against NPE and P. aeruginosa isolates from IAIs and UTIs, including against resistant subsets, and will provide important coverage for IAIs or UTIs caused by β-lactam-resistant, MDR, and KPC-positive Gram-negative bacilli.
Abstract: Objectives Antimicrobial resistance, including multidrug-resistance (MDR), is increasing, especially among Gram-negative bacilli. New agents are needed to treat infections caused by these pathogens. This report assessed the activity of imipenem/relebactam against Gram-negative bacilli from intraabdominal infections (IAIs) and urinary tract infections (UTIs) submitted to the SMART (Study for Monitoring Antimicrobial Resistance Trends) global surveillance programme in the United States from 2015 to 2017. Methods Broth microdilution MICs for imipenem/relebactam and comparators were determined by a central laboratory against isolates of non-Proteeae Enterobacteriaceae (NPE) and Pseudomonas aeruginosa (P. aeruginosa). Imipenem/relebactam MICs were interpreted using United States Food and Drug Administration (FDA) breakpoints. Results 99.5% of NPE isolates collected from patients with IAIs (n = 3633) and UTIs (n = 3038) were susceptible to imipenem/relebactam, as were 77.9% of imipenem-nonsusceptible, 96.3% of Klebsiella pneumoniae carbapenemase (KPC)-positive, and 98.7% of MDR isolates from IAIs and UTIs combined. A total of 96.7% of IAI isolates (n = 486) and 96.4% of UTI isolates (n = 360) of P. aeruginosa were susceptible to imipenem/relebactam, as were 85.0% of imipenem-nonsusceptible and 87.3% of MDR isolates from IAIs and UTIs combined. Percent susceptibility to imipenem/relebactam for cefepime-, ceftazidime-, and piperacillin-tazobactam-nonsusceptible isolates was 98.3–98.8% for NPE and 87.3–90.0% for P. aeruginosa. Conclusions Imipenem/relebactam demonstrated potent in vitro activity against NPE and P. aeruginosa isolates from IAIs and UTIs, including against resistant subsets, and will provide important coverage for IAIs and UTIs caused by β-lactam-resistant, MDR, and KPC-positive Gram-negative bacilli.
TL;DR: The findings showed the presence of antibiotic resistance in probiotic bacteria isolated from commercially available dietary supplements, as multidrug resistance is a serious emerging issue and the risk of drug resistant gene transfer to commensals or pathogens of the gut is inevitable.
Abstract: Objectives The aim of this study was to evaluate antibiotic susceptibility patterns in commercially available dietary and probiotic supplements. Methods Probiotic strains were isolated from the dietary supplements (designated as sample B, D and V), and multidrug resistance profiles were tested using the Kirby-Bauer test. Minimum inhibitory concentrations and double-disk synergy tests were performed to detect the mechanism of action of the resistance, and the presence of extended spectrum β-lactamase activity (ESBL) was confirmed. Results The isolates Streptococcus faecalis and Bacillus mesentericus (both from sample B) were found to be resistant to penicillin G, Lactobacillus acidophilus (sample D) was resistant to ampicillin, and all the isolates from samples B, D and V were resistant to ceftazidime. The isolates Lactobacillus sporogenes, S. faecalis, B. mesentericus from sample B, Lactobacillus. rhamnosus, Saccharomyces boulardii from sample D, and L. sporogenes (sample V) were resistant to erythromycin. Conclusions The findings showed the presence of antibiotic resistance in probiotic bacteria isolated from commercially available dietary supplements. Because multidrug resistance is a serious emerging issue, and the risk of drug-resistant gene transfer to commensals or pathogens of the gut is inevitable, the safety of probiotics has become a major criterion of interest. The findings of this study would serve as a platform for further screening and characterization of the determinants of antibiotic resistance and the genetic mechanisms of resistance.
TL;DR: Cefiderocol for XDR/PDR-Ab infections might be reconsidered, especially in light of the recent disappointing results of CREDIBLE-CR study.
Abstract: Objective This study presents real-life experience with cefiderocol used on a compassionate basis for treatment of three patients with severe infections caused by extensively/pan-drug resistant (XDR/PDR) Acinetobacter baumannii (Ab). Methods Serum bactericidal activity was determined and considered as a surrogate of cefiderocol susceptibility. Results Clinical improvement and microbiological eradication of A. baumannii were observed in all three patients, who were affected by extremely complex conditions either for type of infection, adverse effect or resistance profile of A. baumannii. Conclusion Cefiderocol for XDR/PDR-Ab infections might be reconsidered, especially in light of the recent disappointing results of the CREDIBLE-CR study.
TL;DR: The study identified policy gaps including an explicit financing modality, specifications for antimicrobial stewardship in the veterinary sector and rigorous operational and monitoring and evaluation frameworks.
Abstract: Objectives In 2015, the World Health Organization (WHO) released its global action plan (GAP) on antimicrobial resistance (AMR) as a blueprint for the design of national action plans for AMR containment. Bangladesh, with 80% rural household ownership of at least one livestock, introduced its national action plan in May 2017. The objective of this study was two-fold: (i) to perform a policy content evaluation of the Bangladesh National Action Plan (BNAP) against the GAP with a focus on veterinary AMR containment strategies; and (ii) to assess the evidence on the implementation of veterinary AMR containment strategies of the BNAP. Methods The BNAP was evaluated against the GAP to identify commonalities and policy gaps. A scoping review of peer-reviewed and grey literature was performed to identity evidence of policy implementation and practice gaps. Results The BNAP is strongly aligned with the GAP. However, the study identified policy gaps, including an explicit financing modality, specifications for antimicrobial stewardship (AMS) in the veterinary sector, and rigorous operational and monitoring & evaluation frameworks. More evidence on implementation is needed in terms of incorporation of AMR in the curriculum of veterinarians, AMS plans throughout the veterinary sector, and infection prevention and control protocols and implementation. Conclusion Closing the identified gaps is essential for successful veterinary AMR containment in Bangladesh but will require sustained and significant investment in institutional and human resource development in the coming years.
TL;DR: ST11 K. pneumoniae strains of KL64 was becoming a newly emerged superbug with more resistance and virulence genes in China, which was significant different from other countries, and should be alert the dissemination of this subclone.
Abstract: Objectives ST11 Klebsiella pneumoniae is among the most important clinical pathogens in China, and KL47 and KL64 are the dominant K types of these strains. Understanding the genomic characteristics of these strains would be critical to their anti-infection treatment. Methods There were 364 genome sequences of ST11 K. pneumoniae strains isolated and collected from 13 countries from 2003 to 2018. These genome sequences included 338 downloaded from the National Center for Biotechnology Information (NCBI) database and 26 newly sequenced. Phylogenetic analyses of pan-genome and unique genes, and resistance and virulence gene analyses, were carried out to elucidate the molecular characteristics of these strains. Results A total of 19 732 genes were identified from the 364 ST11 strains, and the pan-genome was open, indicating the genetic diversity of ST11 K. pneumoniae. These strains were clustered into three clades. Clade 1 contained the most various K types (14/15, 93.3%) and unique genes. KL47 and KL64 were the dominant K types of clades 2 and 3, accounting for 100% and 99.4% of strains in each clade, respectively. KL64 strains contained the most virulence genes, including iucA and rmpA, and the two genes tend to coexist. In addition, strains in clade 1 were isolated from all 13 countries; the strains in clades 2 and 3 were isolated mainly from China. Conclusions The ST11 K. pneumoniae strain of KL64 is a newly emerging superbug, with more resistance and virulence genes in China; this was significantly different from other countries, and we should be alert to the dissemination of this subclone.