Despite having a reputation of low virulence, Acinetobacter baumannii is an emerging multidrug-resistant (MDR) pathogen responsible for community- and hospital-acquired infections that are difficult ...to control and treat. Interest in this pathogen emerged about one decade ago because of its natural MDR phenotype, its capability of acquiring new mechanisms of resistance and the existence of nosocomial outbreaks. Recent advances in molecular biology, including full genome sequencing of several A. baumannii isolates, has led to the discovery of the extraordinary plasticity of their genomes, which is linked to their great propensity to adapt to any environment, including hospitals. In this context, as well as the increasing antimicrobial resistance amongst A. baumannii isolates to the last-line antibiotics carbapenems and colistin, therapeutic options are very limited or absent in some cases of infections with pandrug-resistant bacteria. However, a large proportion of patients may be colonised by such MDR bacteria without any sign of infection, leading to a recurrent question for clinicians as to whether antibiotic treatment should be given and will be effective in the presence of resistance mechanisms. The worldwide emergence of A. baumannii strains resistant to colistin is worrying and the increasing use of colistin to treat infections caused by MDR bacteria will inevitably increase the recovery rate of colistin-resistant isolates in the future. Current knowledge about A. baumannii, including biological and epidemiological aspects as well as resistance to antibiotics and antibiotic therapy, are reviewed in this article, in addition to therapeutic recommendations.
Acinetobacter spp. are ubiquitous gram negative and non-fermenting coccobacilli that have the ability to occupy several ecological niches including environment, animals and human. Among the different ...species, Acinetobacter baumannii has evolved as global pathogen causing wide range of infection. Since the implementation of molecular techniques, the habitat and the role of non-baumannii Acinetobacter in human infection have been elucidated. In addition, several new species have been described. In the present review, we summarize the recent data about the natural reservoir of non-baumannii Acinetobacter including the novel species that have been described for the first time from environmental sources and reported during the last years.
The long-term benefits of pneumococcal conjugate vaccines (PCVs) remain unknown because of serotype replacement. We aimed to estimate the effect of PCV implementation on invasive pneumococcal disease ...incidence in France.
We did a quasi-experimental interrupted time-series analysis using data from a French national prospective surveillance system. We included all invasive pneumococcal disease cases in children and adults from more than 250 participating hospitals between Jan 1, 2001, and Dec 31, 2017. The primary outcome was incidence of invasive pneumococcal disease (meningitis and non-meningitis) over time, analysed by segmented regression with autoregressive error. Isolates were serotyped by latex agglutination with antiserum samples.
We included 75 903 patients with invasive pneumococcal disease, including 4302 (5·7%) children younger than 2 years and 37 534 (49·4%) adults aged 65 years or older. Before PCV7 implementation, the estimated monthly incidence of invasive pneumococcal disease was 0·78 cases per 100 000 inhabitants, which did not change significantly up to May, 2010. PCV13 implementation in 2010 was followed by a significant decrease in the incidence of invasive pneumococcal disease (−1·5% per month, 95% CI −2·2 to −0·8), reaching an estimated monthly incidence of 0·52 cases per 100 000 inhabitants in December, 2014. From January, 2015, the incidence rebounded (1·8% per month, 95% CI 1·0 to 2·6), reaching an estimated monthly incidence of 0·73 cases per 100 000 inhabitants in December, 2017. The estimated monthly incidence increased from 0·93 cases per 100 000 in December, 2014, to 1·73 cases per 100 000 in December, 2017, for children younger than 2 years, and from 1·54 cases per 100 000 in December, 2014, to 2·08 cases per 100 000 in December, 2017, for adults aged 65 years or older. The main non-PCV13 serotypes involved in the increase were 24F in young children and 12F, 22F, 9N, and 8 in adults aged 65 years or older.
PCV13 implementation led to a major reduction in the incidence of invasive pneumococcal disease. However, a rebound in cases among children and adults since 2015, driven by several emerging non-PCV13 serotypes, jeopardises the long-term PCV benefits. These findings, if confirmed in the coming years, should be considered in the development of next-generation PCVs and might guide policy makers in the selection of future pneumococcal vaccines.
Foundation for Medical Research; Pfizer, BioMérieux, Sanofi for the Regional Observatory of Pneumococci.
Highlights • The human gut can harbour clonally unrelated colistin-resistant K. pneumoniae. • Mutation in mgrB is an emerging mechanism associated with colistin resistance. • mgrB mutations account ...for higher resistance than mutations in pmrAB or phoPQ.
Summary Background Buruli ulcer, caused by Mycobacterium ulcerans , was identified as a neglected emerging infectious disease by WHO in 1998. Although Buruli ulcer is the third most common ...mycobacterial disease worldwide, understanding of the disease is incomplete. We analysed a large cohort of laboratory-confirmed cases of Buruli ulcer from Pobè, Benin, to provide a comprehensive description of the clinical presentation of the disease, its variation with age and sex, and its effect on the occurrence of permanent functional sequelae. Methods Between Jan 1, 2005, and Dec 31, 2011, we prospectively collected clinical and laboratory data from all patients with Buruli ulcer diagnosed at the Centre de Dépistage et de Traitement de l'Ulcère de Buruli in Pobè, Benin. We followed up patients to assess the frequency of permanent functional sequelae. All analyses were done on cases that were laboratory confirmed. Findings 1227 cases of laboratory-confirmed Buruli ulcer were included in the analysis. Typically, patients with Buruli ulcer were children (median age at diagnosis 12 years) presenting with a unique (1172 96%) large (≥15 cm, 444 36%) ulcerative (805 66%) lesion of the lower limb (733 60%). Atypical clinical presentation of Buruli ulcer included Buruli ulcer osteomyelitis with no identifiable present or past Buruli ulcer skin lesions, which was recorded in at least 14 patients. The sex ratio of Buruli ulcer widely varied with age, with male patients accounting for 57% (n=427) of patients aged 15 years and younger, but only 33% (n=158) of those older than 15 years (odds ratio OR 2·59, 95% CI 2·04–3·30). Clinical presentation of Buruli ulcer was significantly dependent on age and sex. 54 (9%) male patients had Buruli ulcer osteomyelitis, whereas only 28 (4%) of female patients did (OR 2·21, 95% CI 1·39–3·59). 1 year after treatment, 229 (22% of 1043 with follow-up information) patients presented with permanent functional sequelae. Presentation with oedema, osteomyelitis, or large (≥15 cm in diameter), or multifocal lesions was significantly associated with occurrence of permanent functional sequelae (OR 7·64, 95% CI 5·29–11·31) and operationally defines severe Buruli ulcer. Interpretation Our findings have important clinical implications for daily practice, including enhanced surveillance for early detection of osteomyelitis in boys; systematic search for M ulcerans in osteomyelitis cases of non-specific aspect in areas endemic for Buruli ulcer; and specific disability prevention for patients presenting with osteomyelitis, oedema, or multifocal or large lesions. Our findings also suggest a crucial underestimation of the burden of Buruli ulcer in Africa and raise key questions about the contribution of environmental and physiopathological factors to the recorded heterogeneity of the clinical presentation of Buruli ulcer. Funding Agence Nationale de la Recherche (ANR), Fondation Raoul Follereau, Fondation pour la Recherche Médicale (FRM), and Institut des Maladies Génétiques (IMAGINE).
•Of all the P. aeruginosa isolates, 20.9% were MDR and 20.7% were XDR.•Latin America had the highest proportion of all resistant isolates.•Overall, P. aeruginosa isolates showed high susceptibility ...(90.9%) to CAZ-AVI.•MDR (59.6%) and XDR isolates (60.7%) had lower susceptibility to CAZ-AVI.•Only colistin showed high susceptibility (>98.3%) across all P. aeruginosa isolates.
The objective of this study was to assess the distribution and antimicrobial susceptibility of Pseudomonas aeruginosa isolates against ceftazidime-avibactam (CAZ-AVI) and a panel of comparator agents collected globally and in each region from 2017–2020 from the Antimicrobial Testing Leadership and Surveillance program.
Susceptibility and minimum inhibitory concentration of all P. aeruginosa isolates were determined using broth microdilution methodology according to the Clinical and Laboratory Standards Institute guidelines.
Of the total 29746 isolates of P. aeruginosa collected, 20.9% were multidrug resistant (MDR), 20.7% were extremely drug resistant (XDR), 8.4% were CAZ-AVI-resistant (CAZ-AVI-R), and 3.0% were MBL-positive. Amongst the MBL-positive isolates, the proportion of VIM-positive isolates was highest (77.8%). The highest proportion of MDR (25.5%), XDR (25.0%), MBL-positive (5.7%), and CAZ-AVI-R (12.3%) isolates were in Latin America. Amongst the sources, the highest proportion of isolates were from respiratory sources (43.0%), and the majority of isolates were from non-intensive care unit wards (71.2%). Overall, all P. aeruginosa isolates (90.9%) showed high susceptibility to CAZ-AVI. However, MDR and XDR isolates were less susceptible to CAZ-AVI (≤60.7). The only comparators to which all isolates of P. aeruginosa showed good overall susceptibility were colistin (99.1%) and amikacin (90.5%). However, only colistin was active (≥98.3%) against all the resistant isolates.
CAZ-AVI presents a potential treatment option against P. aeruginosa infections. However, active monitoring and surveillance, especially of the resistant phenotypes, is warranted for effective treatment of infections caused by P. aeruginosa.
Rapid detection of carbapenem-resistant Acinetobacter baumannii strains is critical and will benefit patient care by optimizing antibiotic therapies and preventing outbreaks. Herein we describe the ...development and successful application of a mass spectrometry profile generated by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) that utilized the imipenem antibiotic for the detection of carbapenem resistance in a large series of A. baumannii clinical isolates from France and Algeria. A total of 106 A. baumannii strains including 63 well-characterized carbapenemase-producing and 43 non-carbapenemase-producing strains, as well as 43 control strains (7 carbapenem-resistant and 36 carbapenem-sensitive strains) were studied. After an incubation of bacteria with imipenem for up to 4 h, the mixture was centrifuged and the supernatant analyzed by MALDI-TOF MS. The presence and absence of peaks representing imipenem and its natural metabolite was analyzed. The result was interpreted as positive for carbapenemase production if the specific peak for imipenem at 300.0 m/z disappeared during the incubation time and if the peak of the natural metabolite at 254.0 m/z increased as measured by the area under the curves leading to a ratio between the peak for imipenem and its metabolite being <0.5. This assay, which was applied to the large series of A. baumannii clinical isolates, showed a sensitivity of 100.0% and a specificity of 100.0%. Our study is the first to demonstrate that this quick and simple assay can be used as a routine tool as a point-of-care method for the identification of A. baumannii carbapenemase-producers in an effort to prevent outbreaks and the spread of uncontrollable superbugs.
Mycobacterium ulcerans is the causative agent of Buruli ulcer, a neglected tropical disease found in rural areas of West and Central Africa. Despite the ongoing efforts to tackle Buruli ulcer ...epidemics, the environmental reservoir of its pathogen remains elusive, underscoring the need for new approaches to improving disease prevention and management. In our study, we implemented a local-scale spatial clustering model and deciphered the genetic diversity of the bacteria in a small area of Benin where Buruli ulcer is endemic. Using 179 strain samples from West Africa, we conducted a phylogeographic analysis combining whole-genome sequencing with spatial scan statistics. The 8 distinct genotypes we identified were by no means randomly spread over the studied area. Instead, they were divided into 3 different geographic clusters, associated with landscape characteristics. Our results highlight the ability of M. ulcerans to evolve independently and differentially depending on location in a specific ecologic reservoir.
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