Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA)

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance. The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally. The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria. An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs. The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections). The authors hope that AGORA, involving many of the world's leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs

High prevalence of the arginine catabolic mobile element in carriage isolates of methicillin-resistant Staphylococcus epidermidis

Background The arginine catabolic mobile element (ACME) associated with staphylococcal cassette chromosome mec (SCCmec) in the USA300 clone of community-acquired methicillin-resistant Staphylococcus aureus enhances its fitness and ability to colonize the host. Staphylococcus epidermidis may act as a reservoir of ACME for S. aureus. We assessed the diffusion of ACME in methicillin-resistant S. epidermidis (MRSE) isolates colonizing outpatients. Methods Seventy-eight MRSE strains isolated in outpatients from five countries were characterized by multilocus sequence typing (MLST) and SCCmec typing and screened for the arcA and opp3AB markers of ACME. ACME-arcA and ACME-opp3AB were sequenced. ACME type I from MRSE and USA300 were compared by long-range PCR (LR-PCR). Results Fifty-three (67.9%) MRSE strains carried an ACME element, including 19 (24.4%), 32 (41.0%) and 2 (2.6%) with ACME type I (arcA+/opp3AB+), II (arcA+/opp3AB−) and III (arcA−/opp3AB+), respectively. The prevalence of ACME did not differ between clonal complex 2 (42/60 strains) and other sequence types (11/18 strains, P = 0.7), with MLST data suggesting frequent intraspecies acquisition. ACME-arcA sequences were highly conserved, whereas ACME-opp3AB displayed 11 distinct allotypes. ACME was found in 14/29, 9/11 and 30/37 strains with type IV, type V and non-typeable SCCmec, respectively (P = 0.01). ACME was more frequently associated with ccrC than with ccrAB2 (82.4% versus 60.0%, P = 0.048). LR-PCR indicated structural homologies of ACME I between MRSE and USA300. Conclusions ACME is widely disseminated in MRSE strains colonizing outpatients and may contribute to their spread in a community environment with low antibiotic exposure, as suggested for USA30

Methicillin-Resistant Coagulase-Negative Staphylococci in the Community: High Homology of SCCmec IVa between Staphylococcus epidermidis and Major Clones of Methicillin-Resistant Staphylococcus aureus

Background. Data on community spread of methicillin-resistant coagulase-negative staphylococci (MR-CoNS) are scarce. We assessed their potential role as a reservoir of staphylococcal cassette chromosome mec (SCCmec) IVa, the leading SCCmec subtype in community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Methods. Nasal carriage of MR-CoNS was prospectively investigated in 291 adults at hospital admission. MR-CoNS were characterized by SCCmec typing, long-range polymerase chain reaction (PCR) for SCCmec IV, and multiple-locus variable-number tandem repeat analysis (MLVA) for Staphylococcus epidermidis (MRSE) strains. Three SCCmec IVa elements were fully sequenced. Results. The carriage rate of MR-CoNS was 19.2% (25.9% and 16.5% in patients with and patients without previous exposure to the health care system, respectively; P = .09). MR-CoNS strains (n=83, including 58 MRSE strains with highly heterogeneous MLVA patterns) carried SCCmec type IVa (n=9, all MRSE), other SCCmec IV subtypes (n=9, including 7 MRSE), other SCCmec types (n=15), and nontypeable SCCmec (n=50). Long-range PCR indicated structural homology between SCCmec IV in MRSE and that in MRSA. Complete sequences of SCCmec IVa from 3 MRSE strains were highly homologous to those available for CA-MRSA, including major clones USA300 and USA400. Conclusions. MR-CoNS are probably disseminated in the community, notably in subjects without previous exposure to the health care system. MRSE, the most prevalent species, may act as a reservoir of SCCmec IVa for CA-MRS

CTX-M β-Lactamases in Escherichia coli from Community-acquired Urinary Tract Infections, Cambodia

The prevalence of CTX-M β-lactamases has reached a critical level, which highlights the need for study of their spread in developing countries

Prediction of the intestinal resistome by a three-dimensional structure-based method

The intestinal microbiota is considered to be a major reservoir of antibiotic resistance determinants (ARDs) that could potentially be transferred to bacterial pathogens via mobile genetic elements. Yet, this assumption is poorly supported by empirical evidence due to the distant homologies between known ARDs (mostly from culturable bacteria) and ARDs from the intestinal microbiota. Consequently, an accurate census of intestinal ARDs (that is, the intestinal resistome) has not yet been fully determined. For this purpose, we developed and validated an annotation method (called pairwise comparative modelling) on the basis of a three-dimensional structure (homology comparative modelling), leading to the prediction of 6,095 ARDs in a catalogue of 3.9 million proteins from the human intestinal microbiota. We found that the majority of predicted ARDs (pdARDs) were distantly related to known ARDs (mean amino acid identity 29.8%) and found little evidence supporting their transfer between species. According to the composition of their resistome, we were able to cluster subjects from the MetaHIT cohort (n = 663) into six resistotypes that were connected to the previously described enterotypes. Finally, we found that the relative abundance of pdARDs was positively associated with gene richness, but not when subjects were exposed to antibiotics. Altogether, our results indicate that the majority of intestinal microbiota ARDs can be considered intrinsic to the dominant commensal microbiota and that these genes are rarely shared with bacterial pathogens

Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA)

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance. The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally. The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria. An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs. The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections). The authors hope that AGORA, involving many of the world's leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs

The Human Gut Microbiota in all its States: From Disturbance to Resilience

International audienceThe human gut microbiota is a diverse and dynamic ecosystem that has pleiotropic effects on host physiology. There is increasing evidence that the transition to an industrialized lifestyle has been accompanied by a gradual alteration of human gut microbiota, which is reflected at both compositional and functional levels and is associated with the emergence of chronic diseases. In early life, the gut microbiota undergoes highly dynamic evolution in response to environmental factors, which is less pronounced later in life. Gut microbiota may encounter various acute and continuous, and the response varies greatly between individuals and stressors. Growing interest in this topic has rapidly led to application of novel high resolution approaches that have increased insight into human gut microbiota stability, dynamics and response to disturbances. In the future, detailed longitudinal studies coupled with multi-omics based approaches and clinical outcomes, will help in the prediction of gut microbiome trajectories in response to disturbances and in the identification of preventive solutions to mitigate gut microbiota alterations

Establishing Genotype-to-Phenotype Relationships in Bacteria Causing Hospital-Acquired Pneumonia: A Prelude to the Application of Clinical Metagenomics

Clinical metagenomics (CMg), referred to as the application of next-generation sequencing (NGS) to clinical samples, is a promising tool for the diagnosis of hospital-acquired pneumonia (HAP). Indeed, CMg allows identifying pathogens and antibiotic resistance genes (ARGs), thereby providing the information required for the optimization of the antibiotic regimen. Hence, provided that CMg would be faster than conventional culture, the probabilistic regimen used in HAP could be tailored faster, which should lead to an expected decrease of mortality and morbidity. While the inference of the antibiotic susceptibility testing from metagenomic or even genomic data is challenging, a limited number of antibiotics are used in the probabilistic regimen of HAP (namely beta-lactams, aminoglycosides, fluoroquinolones, glycopeptides and oxazolidinones). Accordingly, based on the perspective of applying CMg to the early diagnostic of HAP, we aimed at reviewing the performances of whole genomic sequencing (WGS) of the main HAP-causing bacteria (Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia and Staphylococcus aureus) for the prediction of susceptibility to the antibiotic families advocated in the probabilistic regimen of HAP