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

Massive Increase, Spread, and Exchange of Extended Spectrum {beta}-Lactamase-Encoding Genes Among Intestinal Enterobacteriaceae in Hospitalized Children With Severe Acute Malnutrition in Niger.

Background. From the time of CTX-M emergence, extended-spectrum β-lactamase-producing enterobacteria (ESBL-E) have spread worldwide in community settings as well as in hospitals, particularly in developing countries. Although their dissemination appears linked to Escherichia coli intestinal carriage, precise paths of this dynamic are largely unknown. Methods. Children from a pediatric renutrition center were prospectively enrolled in a fecal carriage study. Antibiotic exposure was recorded. ESBL-E strains were isolated using selective media from fecal samples obtained at admission and, when negative, also at discharge. ESBL-encoding genes were identified, their environments and plasmids were characterized, and clonality was assessed with polymerase chain reaction-based methods and pulsed-field gel electrophoresis for E. coli and Klebsiella pneumoniae. E. coli strains were subjected to multilocus sequence typing. Results. The ESBL-E carriage rate was 31% at admission in the 55 children enrolled. All children enrolled received antibiotics during hospitalization. Among the ESBL-E-negative children, 16 were resampled at discharge, and the acquisition rate was 94%. The bla(CTX-M-15) gene was found in >90% of the carriers. Genetic environments and plasmid characterization evidenced the roles of a worldwide, previously described, multidrug-resistant region and of IncF plasmids in CTX-M-15 E. coli dissemination. Diversity of CTX-M-15-carrying genetic structures and clonality of acquired ESBL E. coli suggested horizontal genetic transfer and underlined the potential of some ST types for nosocomial cross-transmission. Conclusions. Cross-transmission and high selective pressure lead to very high acquisition of ESBL-E carriage, contributing to dissemination in the community. Strict hygiene measures as well as careful balancing of benefit-risk ratio of current antibiotic policies need to be reevaluated

Acquisition of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) carriage after exposure to systemic antimicrobials during travel: systematic review and meta-analysis

BACKGROUND: International travel is an important risk factor for colonization with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). Antimicrobial use during travel likely amplifies this risk, yet to what extent, and whether it varies by antimicrobial class, has not been established. METHODS: We conducted a systematic review that included prospective cohorts reporting both receipt of systemic antimicrobials and acquired ESBL-PE isolated from stool or rectum during international travel. We performed a random effects meta-analysis to estimate odds of acquiring ESBL-PE due to antimicrobials during travel, overall and by antimicrobial class. RESULTS: Fifteen studies were included. The study population was mainly female travellers from high income countries recruited primarily from travel clinics. Participants travelled most frequently to Asia and Africa with 10% reporting antimicrobial use during travel. The combined odds ratio (OR) for ESBL-PE acquisition during travel was 2.37 for antimicrobial use overall (95% confidence interval [CI], 1.69 to 3.33), but there was substantial heterogeneity between studies. Fluoroquinolones were the antibiotic class associated with the highest combined OR of ESBL-PE acquisition, compared to no antimicrobial use (OR 4.68, 95% CI, 2.34 to 9.37). CONCLUSIONS: The risk of ESBL-PE colonization during travel is increased substantially with exposure to antimicrobials, especially fluoroquinolones. While a small proportion of colonized individuals will develop a resistant infection, there remains the potential for onward spread among returning travellers. Public health efforts to decrease inappropriate antimicrobial usage during travel are warranted

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 app1133132sem informaçãosem informaçã

Selective culture enrichment and sequencing of feces to enhance detection of antimicrobial resistance genes in third-generation cephalosporin resistant Enterobacteriaceae

Metagenomic sequencing of fecal DNA can usefully characterise an individual’s intestinal resistome but is limited by its inability to detect important pathogens that may be present at low abundance, such as carbapenemase or extended-spectrum beta-lactamase producing Enterobacteriaceae. Here we aimed to develop a hybrid protocol to improve detection of resistance genes in Enterobacteriaceae by using a short period of culture enrichment prior to sequencing of DNA extracted directly from the enriched sample. Volunteer feces were spiked with carbapenemase-producing Enterobacteriaceae and incubated in selective broth culture for 6 hours before sequencing. Different DNA extraction methods were compared, including a plasmid extraction protocol to increase the detection of plasmid-associated resistance genes. Although enrichment prior to sequencing increased the detection of carbapenemase genes, the differing growth characteristics of the spike organisms precluded accurate quantification of their concentration prior to culture. Plasmid extraction increased detection of resistance genes present on plasmids, but the effects were heterogeneous and dependent on plasmid size. Our results demonstrate methods of improving the limit of detection of selected resistance mechanisms in a fecal resistome assay, but they also highlight the difficulties in using these techniques for accurate quantification and should inform future efforts to achieve this goa

Rectal Carriage of Extended-Spectrum Beta-Lactamase-Producing Gram-Negative Bacilli in Community Settings in Madagascar

BACKGROUND: Extended-spectrum ß-lactamase-producing Enterobacteria (ESBL-PE) emerged at the end of the 1980s, causing nosocomial outbreaks and/or hyperendemic situations in hospitals and long-term care facilities. In recent years, community-acquired infections due to ESBL-PE have spread worldwide, especially across developing countries including Madagascar. OBJECTIVES: This study aimed to determine the prevalence and risk factors of intestinal carriage of ESBL-PE in the community of Antananarivo. METHODS: Non-hospitalized patients were recruited in three health centers in different socio economic settings. Fresh stool collected were immediately plated on Drigalski agar containing 3 mg/liter of ceftriaxone. Gram-negative bacilli species were identified and ESBL production was tested by a double disk diffusion (cefotaxime and ceftazidime +/- clavulanate) assay. Characterization of ESBLs were perfomed by PCR and direct sequencing . Molecular epidemiology was analysed by Rep-PCR and ERIC-PCR. RESULTS: 484 patients were screened (sex ratio  = 1.03, median age 28 years). 53 ESBL-PE were isolated from 49 patients (carrier rate 10.1%). The isolates included Escherichia coli (31), Klebsiella pneumoniae (14), Enterobacter cloacae (3), Citrobacter freundii (3), Kluyvera spp. (1) and Pantoae sp.(1). In multivariate analysis, only the socioeconomic status of the head of household was independently associated with ESBL-PE carriage, poverty being the predominant risk factor. CONCLUSIONS: The prevalence of carriage of ESBL in the community of Antananarivo is one of the highest reported worldwide. This alarming spread of resistance genes should be stopped urgently by improving hygiene and streamlining the distribution and consumption of antibiotics

Klebsiella pneumoniae related community-acquired acute lower respiratory infections in CAMBODIA: clinical characteristics and treatment

<p>Abstract</p> <p>Background</p> <p>In many Asian countries, <it>Klebsiella pneumoniae </it>(KP) is the second pathogen responsible for community-acquired pneumonia. Yet, very little is known about <it>KP </it>etiology in ALRI in Cambodia, a country that has one of the weakest medical infrastructures in the region. We present here the first clinico-radiological description of <it>KP </it>community-acquired ALRI in hospitalized Cambodian patients.</p> <p>Methods</p> <p>Through ALRI surveillance in two provincial hospitals, <it>KP </it>was isolated from sputum and blood cultures, and identified by API20E gallery from patients ≥ 5 years-old with fever and respiratory symptoms onset ≤14 days. Antibiotics susceptibility testing was provided systematically to clinicians when bacteria were isolated. We collected patients' clinical, radiological and microbiological data and their outcome 3 months after discharge. We also compared <it>KP</it>-related with other bacteria-related ALRI to determine risk factors for <it>KP </it>infection.</p> <p>Results</p> <p>From April 2007 to December 2009, 2315 ALRI patients ≥ 5 years-old were enrolled including 587 whose bacterial etiology could be assigned. Of these, 47 (8.0%) had <it>KP </it>infection; their median age was 55 years and 68.1% were females. Reported prior medication was high (42.5%). Patients' chest radiographs showed pneumonia (61.3% including 39% that were necrotizing), preexisting parenchyma lesions (29.5%) and pleural effusions alone (4.5%) and normal parenchyma (4.5%). Five patients had severe conditions on admission and one patient died during hospitalization. Of the 39 patients that were hospital discharged, 14 died including 12 within 1 month after discharge. Only 13 patients (28%) received an appropriate antibiotherapy. Extended-spectrum beta-lactamases (ESBL) - producing strains were found in 8 (17.0%) patients. Female gender (Odds ratio (OR) 2.1; <it>p </it>= 0.04) and diabetes mellitus (OR 3.1; <it>p </it>= 0.03) were independent risk factors for <it>KP</it>-related ALRI.</p> <p>Conclusions</p> <p><it>KP </it>ALRI in Cambodia has high fatality rate, are more frequently found in women, and should be considered in diabetic patients. The extremely high frequency of ESBL-producing strains in the study is alarming in the context of uncontrolled antibiotic consumption and in absence of microbiology capacity in most public-sector hospitals.</p

Complete Nucleotide Sequence of CTX-M-15-Plasmids from Clinical Escherichia coli Isolates: Insertional Events of Transposons and Insertion Sequences

BACKGROUND: CTX-M-producing Escherichia coli strains are regarded as major global pathogens. METHODOLOGY/PRINCIPAL FINDINGS: The nucleotide sequence of three plasmids (pEC_B24: 73801-bp; pEC_L8: 118525-bp and pEC_L46: 144871-bp) from Escherichia coli isolates obtained from patients with urinary tract infections and one plasmid (pEC_Bactec: 92970-bp) from an Escherichia coli strain isolated from the joint of a horse with arthritis were determined. Plasmid pEC_Bactec belongs to the IncI1 group and carries two resistance genes: bla(TEM-1) and bla(CTX-M-15). It shares more than 90% homology with a previously published bla(CTX-M)-plasmid from E. coli of human origin. Plasmid pEC_B24 belongs to the IncFII group whereas plasmids pEC_L8 and pEC_L46 represent a fusion of two replicons of type FII and FIA. On the pEC_B24 backbone, two resistance genes, bla(TEM-1) and bla(CTX-M-15), were found. Six resistance genes, bla(TEM-1), bla(CTX-M-15), bla(OXA-1), aac6'-lb-cr, tetA and catB4, were detected on the pEC_L8 backbone. The same antimicrobial drug resistance genes, with the exception of tetA, were also identified on the pEC_L46 backbone. Genome analysis of all 4 plasmids studied provides evidence of a seemingly frequent transposition event of the bla(CTX-M-15)-ISEcp1 element. This element seems to have a preferred insertion site at the tnpA gene of a bla(TEM)-carrying Tn3-like transposon, the latter itself being inserted by a transposition event. The IS26-composite transposon, which contains the bla(OXA-1), aac6'-lb-cr and catB4 genes, was inserted into plasmids pEC_L8 and pEC_L46 by homologous recombination rather than a transposition event. Results obtained for pEC_L46 indicated that IS26 also plays an important role in structural rearrangements of the plasmid backbone and seems to facilitate the mobilisation of fragments from other plasmids. CONCLUSIONS: Collectively, these data suggests that IS26 together with ISEcp1 could play a critical role in the evolution of diverse multiresistant plasmids found in clinical Enterobacteriaceae