Plasmid persistence in bacterial populations is strongly influenced by the fitness effects associated with plasmid carriage. However, plasmid fitness effects in wild-type bacterial hosts remain ...largely unexplored. In this study, we determined the fitness effects of the major antibiotic resistance plasmid pOXA-48_K8 in wild-type, ecologically compatible enterobacterial isolates from the human gut microbiota. Our results show that although pOXA-48_K8 produced an overall reduction in bacterial fitness, it produced small effects in most bacterial hosts, and even beneficial effects in several isolates. Moreover, genomic results showed a link between pOXA-48_K8 fitness effects and bacterial phylogeny, helping to explain plasmid epidemiology. Incorporating our fitness results into a simple population dynamics model revealed a new set of conditions for plasmid stability in bacterial communities, with plasmid persistence increasing with bacterial diversity and becoming less dependent on conjugation. These results help to explain the high prevalence of plasmids in the greatly diverse natural microbial communities.
To describe current antimicrobial resistance in ESKAPE Gram-negative microorganisms and their situation in the ICUs, the implication of the so-called high-risk clones (HiRCs) involved in the spread ...of antimicrobial resistance as well as relevance of the COVID-19 pandemic in the potential increase of resistance.
Extended-spectrum and carbapenemase producing Enterobacterales and multidrug and extensive drug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii have increased worldwide. Sequence type (ST)131 Escherichia coli, ST258, ST11, ST10, ST147 and ST307 Klebsiella pneumoniae, ST111, ST175, ST235 and ST244 P. aeruginosa HiRCs are responsible for this increase in the ICUs, and some of them are implicated in the emergence of resistance mechanisms affecting new antimicrobials. A similar situation can be found with European clonal complex 1 and clonal complex 2 of A. baumannii. The high use of antimicrobials during the COVID-19 pandemic, particularly in ICUs, might have a negative influence in future trends of antimicrobial resistance.
The increase of antimicrobial resistance in ICUs is mainly due to the spread of HiRCs and is exemplified with the ESKAPE Gram-negative microorganisms. The COVID-19 pandemic might have a negative impact in the increase of antimicrobial resistance and should be monitored through specific surveillance studies in ICUs.
Bronchiectasis in adults is a chronic disorder associated with poor quality of life and frequent exacerbations in many patients. There have been no previous international guidelines.The European ...Respiratory Society guidelines for the management of adult bronchiectasis describe the appropriate investigation and treatment strategies determined by a systematic review of the literature.A multidisciplinary group representing respiratory medicine, microbiology, physiotherapy, thoracic surgery, primary care, methodology and patients considered the most relevant clinical questions (for both clinicians and patients) related to management of bronchiectasis. Nine key clinical questions were generated and a systematic review was conducted to identify published systematic reviews, randomised clinical trials and observational studies that answered these questions. We used the GRADE approach to define the quality of the evidence and the level of recommendations. The resulting guideline addresses the investigation of underlying causes of bronchiectasis, treatment of exacerbations, pathogen eradication, long term antibiotic treatment, anti-inflammatories, mucoactive drugs, bronchodilators, surgical treatment and respiratory physiotherapy.These recommendations can be used to benchmark quality of care for people with bronchiectasis across Europe and to improve outcomes.
Antibiotic-resistant organisms enter into water environments from human and animal sources. These bacteria are able to spread their genes into water-indigenous microbes, which also contain resistance ...genes. On the contrary, many antibiotics from industrial origin circulate in water environments, potentially altering microbial ecosystems. Risk assessment protocols for antibiotics and resistant bacteria in water, based on better systems for antibiotics detection and antibiotic-resistance microbial source tracking, are starting to be discussed. Methods to reduce resistant bacterial load in wastewaters, and the amount of antimicrobial agents, in most cases originated in hospitals and farms, include optimization of disinfection procedures and management of wastewater and manure. A policy for preventing mixing human-originated and animal-originated bacteria with environmental organisms seems advisable.
Abstract
Background
In the late 1990s, as a response to rising antimicrobial resistance (AMR), an independent multinational, interdisciplinary group was formed specifically targeting primary care ...antibiotic prescribing for community-acquired respiratory tract infections (CA-RTIs). The group comprised senior clinicians from Canada, Israel, Spain, Sweden, UK and USA. The group’s objectives were to provide recommendations for antibiotic stewardship in the community because, whilst it was widely accepted that inappropriate antibiotic use was contributing to AMR, it remained difficult to change prescribing behaviour. The group aimed to identify principles underlying appropriate antibiotic prescribing and guideline formulation to reduce morbidity from CA-RTIs, limit therapeutic failure and, importantly, curb AMR emergence. The group published a report in 2002, which has become known as the Consensus Principles.
Objectives
(i) To consider the relevance of the Consensus Principles in 2022 by reviewing current global approaches to rising AMR. A wide range of factors, such as antibiotic overuse, most recently seen in COVID-19 patients, are still driving rising AMR even though there has been a high-level international response to the AMR threat; and (ii) as an introduction to this Supplement, which reports the findings of analyses of how AMR is being addressed in nine disparate countries (Brazil, India, Kuwait, Mexico, Pakistan, Russia, Saudi Arabia, Türkiye and Vietnam). Understanding how these initiatives are being pursued in different countries helps identify areas where more information is needed.
Conclusions
Adherence to the Consensus Principles remains as important now as it was in 2002. Achieving appropriate antibiotic prescribing is a vital objective in order that the right patient receives the right antibiotics at the right time to ensure optimal clinical outcomes while at the same time helping to limit further increases in AMR.
The CTX-M β-lactamase pandemic Cantón, Rafael; Coque, Teresa M
Current opinion in microbiology,
10/2006, Letnik:
9, Številka:
5
Journal Article
Recenzirano
In the past decade CTX-M enzymes have become the most prevalent extended-spectrum β-lactamases, both in nosocomial and in community settings. The insertion sequences (ISs) IS
Ecp1 and IS
CR1 ...(formerly common region 1 CR1 or orf513) appear to enable the mobilization of chromosomal β-lactamase
Kluyvera species genes, which display high homology with
bla
CTX-Ms. These ISs are preferentially linked to specific genes: IS
Ecp1 to most
bla
CTX-Ms, and IS
CR1 to
bla
CTX-M-2 or
bla
CTX-M-9. The
bla
CTX-M genes embedded in class 1 integrons bearing IS
CR1 are associated with different Tn
402-derivatives, and often with mercury Tn
21-like transposons. The
bla
CTX-M genes linked to IS
Ecp1 are often located in multidrug resistance regions containing different transposons and ISs. These structures have been located in narrow and broad host-range plasmids belonging to the same incompatibility groups as those of early antibiotic resistance plasmids. These plasmids frequently carry aminoglycoside, tetracycline, sulfonamide or fluoroquinolone resistance genes
qnr and/or
aac(
6′)
-Ib-cr, which would have facilitated the dissemination of
bla
CTX-M genes because of co-selection processes. In
Escherichia coli, they are frequently carried in well-adapted phylogenetic groups with particular virulence-factor genotypes. Also, dissemination has been associated with different clones (CTX-M-9 or CTX-M-14 producers) or epidemic clones associated with specific enzymes such as CTX-M-15. All these events might have contributed to the current pandemic CTX-M β-lactamase scenario.
Highlights ► Multidrug-resistant bacteria has increased over the past years. ► Co-resistance involves acquisition of mutations in different genetic loci and/or transfer of several resistance genes ...into the same bacteria. ► Isolates with co-resistance can be selected with different antimicrobials exerting co-selection processes. ► Cycling and mixing practices of antimicrobial use might facilitate co-resistance and co-selection processes. ► Co-resistance and co-selection processes increase the opportunity for persistence of the bacteria and the resistance genes.
Abstract
Within a susceptible wild-type population, a small fraction of cells, even <10−9, is not affected when challenged by an antimicrobial agent. This subpopulation has mutations that impede ...antimicrobial action, allowing their selection during clinical treatment. Emergence of resistance occurs in the frame of a selective compartment termed a mutant selection window (MSW). The lower margin corresponds to the minimum inhibitory concentration of the susceptible cells, whereas the upper boundary, named the mutant prevention concentration (MPC), restricts the growth of the entire population, including that of the resistant mutants. By combining pharmacokinetic/pharmacodynamic concepts and an MPC strategy, the selection of resistant mutants can be limited. Early treatment avoiding an increase of the inoculum size as well as a regimen restricting the time within the MSW can reduce the probability of emergence of the resistant mutants. Physiological and, possibly, genetic adaptation in biofilms and a high proportion of mutator clones that may arise during chronic infections influence the emergence of resistant mutants. Moreover, a resistant population can emerge in a specific selective compartment after acquiring a resistance trait by horizontal gene transfer, but this may also be avoided to some extent when the MPC is reached. Known linkage between antimicrobial use and resistance should encourage actions for the design of antimicrobial treatment regimens that minimize the emergence of resistance.
Emergence of a resistant bacterial subpopulation within a susceptible wild-type population can be restricted with a regimen using an antibiotic dose that is sufficiently high to inhibit both susceptible and resistant bacteria.
Summary Background The best available treatment against carbapenemase-producing Enterobacteriaceae (CPE) is unknown. The objective of this study was to investigate the effect of appropriate therapy ...and of appropriate combination therapy on mortality of patients with bloodstream infections (BSIs) due to CPE. Methods In this retrospective cohort study, we included patients with clinically significant monomicrobial BSIs due to CPE from the INCREMENT cohort, recruited from 26 tertiary hospitals in ten countries. Exclusion criteria were missing key data, death sooner than 24 h after the index date, therapy with an active antibiotic for at least 2 days when blood cultures were taken, and subsequent episodes in the same patient. We compared 30 day all-cause mortality between patients receiving appropriate (including an active drug against the blood isolate and started in the first 5 days after infection) or inappropriate therapy, and for patients receiving appropriate therapy, between those receiving active monotherapy (only one active drug) or combination therapy (more than one). We used a propensity score for receiving combination therapy and a validated mortality score (INCREMENT-CPE mortality score) to control for confounders in Cox regression analyses. We stratified analyses of combination therapy according to INCREMENT-CPE mortality score (0–7 low mortality score vs 8–15 high mortality score). INCREMENT is registered with ClinicalTrials.gov , number NCT01764490. Findings Between Jan 1, 2004, and Dec 31, 2013, 480 patients with BSIs due to CPE were enrolled in the INCREMENT cohort, of whom we included 437 (91%) in this study. 343 (78%) patients received appropriate therapy compared with 94 (22%) who received inappropriate therapy. The most frequent organism was Klebsiella pneumoniae (375 86% of 437; 291 85% of 343 patients receiving appropriate therapy vs 84 89% of 94 receiving inappropriate therapy) and the most frequent carbapenemase was K pneumoniae carbapenemase (329 75%; 253 74% vs 76 81%). Appropriate therapy was associated with lower mortality than was inappropriate therapy (132 38·5% of 343 patients died vs 57 60·6% of 94; absolute difference 22·1% 95% CI 11·0–33·3; adjusted hazard ratio HR 0·45 95% CI 0·33–0·62; p<0·0001). Among those receiving appropriate therapy, 135 (39%) received combination therapy and 208 (61%) received monotherapy. Overall mortality was not different between those receiving combination therapy or monotherapy (47 35% of 135 vs 85 41% of 208; adjusted HR 1·63 95% CI 0·67–3·91; p=0·28). However, combination therapy was associated with lower mortality than was monotherapy in the high-mortality-score stratum (30 48% of 63 vs 64 62% of 103; adjusted HR 0·56 0·34–0·91; p=0·02), but not in the low-mortality-score stratum (17 24% of 72 vs 21 20% of 105; adjusted odds ratio 1·21 0·56–2·56; p=0·62). Interpretation Appropriate therapy was associated with a protective effect on mortality among patients with BSIs due to CPE. Combination therapy was associated with improved survival only in patients with a high mortality score. Patients with BSIs due to CPE should receive active therapy as soon as they are diagnosed, and monotherapy should be considered for those in the low-mortality-score stratum. Funding Spanish Network for Research in Infectious Diseases, European Development Regional Fund, Instituto de Salud Carlos III, and Innovative Medicines Initiative.
Emergence of epidemic clones and antibiotic resistance development compromises the management of Pseudomonas aeruginosa cystic fibrosis (CF) chronic respiratory infections. Whole genome sequencing ...(WGS) was used to decipher the phylogeny, interpatient dissemination, WGS mutator genotypes (mutome) and resistome of a widespread clone (CC274), in isolates from two highly-distant countries, Australia and Spain, covering an 18-year period. The coexistence of two divergent CC274 clonal lineages was revealed, but without evident geographical barrier; phylogenetic reconstructions and mutational resistome demonstrated the interpatient transmission of mutators. The extraordinary capacity of P. aeruginosa to develop resistance was evidenced by the emergence of mutations in >100 genes related to antibiotic resistance during the evolution of CC274, catalyzed by mutator phenotypes. While the presence of classical mutational resistance mechanisms was confirmed and correlated with resistance phenotypes, results also showed a major role of unexpected mutations. Among them, PBP3 mutations, shaping up β-lactam resistance, were noteworthy. A high selective pressure for mexZ mutations was evidenced, but we showed for the first time that high-level aminoglycoside resistance in CF is likely driven by mutations in fusA1/fusA2, coding for elongation factor G. Altogether, our results provide valuable information for understanding the evolution of the mutational resistome of CF P. aeruginosa.
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