Antibiotic resistance surveillance systems: A review.

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 ß-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.

Prospective case-control analysis of the aetiologies of acute undifferentiated fever in Vietnam.

Acute undifferentiated fever (AUF) is frequently observed in tropical settings, but diagnosing the cause of AUF is often a challenge for local physicians and the physicians treating returning travellers. We conducted a case-control study in central Vietnam in 2016. A total of 378 febrile adult patients (AUFs) with a fever for ≤21 days, no evidence of localized infection and negative screening tests for dengue and malaria, and 384 afebrile adult patients (Controls) were prospectively enrolled. Whole blood, plasma, eschar swab, throat swab and urine specimens were collected and analysed. Quantitative PCR and RT-PCR were used to test for 55 bacteria, viruses and their subtypes. Serological tests were also used to test for rickettsial agents. The most common aetiology was influenza virus (20.9% in AUFs vs. 0% in Controls), followed by rickettsial agents (mainly Orientia tsutsugamushi and Rickettsia typhi) (10.8% vs. 0.3%), dengue virus (7.7% vs. 0.5%), Leptospira (4.8% vs. 0.8%), adenovirus (4.8% vs. 1.0%), and enterovirus (2.1% vs. 0%) (p < .05). The real proportion of dengue in AUF cases was underestimated because patients with dengue-positive rapid diagnosis tests were excluded from the study. The emerging agent Rickettsia felis, which had not been previously observed in Vietnam, was detected in this study. In total, 216 patients (57.1%) were given causative diagnoses, comprising 143 (66.2%) monoinfections and 73 (33.8%) coinfections. The infections caused by these agents should be considered in clinical practice and further studies. Additionally, agents susceptible to doxycycline were detected in 15.6% of AUFs; thus, this drug should be included in the panel used to treat AUF patients.

Extremely and pandrug-resistant bacteria extra-deaths: myth or reality?

In 2009, the European Centre for Disease Prevention and Control (ECDC) estimated that multidrug-resistant (MDR) bacterial infections were responsible for 25,000 extra-deaths per year. In 2015, another report estimated that 12,500 extra-deaths were attributable to MDR bacteria every year in France. Recently, the United Nations claimed that resistance to antimicrobials was a global scourge, forecasting 10 million deaths in 2050. Surprisingly, our antibiotic resistance surveillance system in Marseille, France, did not allowed us to observe similar trends. We herein compared our data on extremely drug-resistant (XDR)/pandrug-resistant (PDR) patient extra-deaths to evaluations and predictions from these reports. First, we retrospectively collect and analyze antibiotic resistance data produced by our settings between November 2009 and March 2015 to look for 30-day deaths attributable to XDR/PDR strains belonging to 11 bacterial species/genus. In parallel, we performed a PubMed literature search to look for articles published prior to July 2016 and describing human deaths due to PDR strains. Overall, 35,723 patients were infected by at least one bacterial species/genus of interest and 85 by XDR/PDR strains. Of these patients, only one death was attributable to a XDR bacterial infection in a patient with strong comorbidities and two consecutive septic shocks. Our literature review shows that only four articles described human deaths due to PDR bacteria. All together, these data allowed us to conclude that there is a large discrepancy between the real count of deaths attributable to XDR/PDR bacteria and alarmist predictions.

Parallel Decline of Malaria and Rickettsia felis Infections in Senegal.

Rickettsia felis is a common emerging pathogen in sub-Saharan Africa. Comparing dynamics of morbidities due to malaria and R. felis infections in two Senegalese villages, we found a strong and significant correlation between them. Malaria morbidity is strongly decreasing because of the implementation of long-lasting insecticidal nets, so we hypothesize that the same measure may decrease the R. felis infections.

Evaluating the Clinical Burden and Mortality Attributable to Antibiotic Resistance: The Disparity of Empirical Data and Simple Model Estimations.

Given the proliferation of cataclysmic predictions about antibiotic resistance, cases of which are estimated to amount to 12500 per year in France, we herein decided to compare the empirical clinical microbiology data from our institution with estimates and predictions from 10 major international scientific articles and reports. The analysis of 7 years of antibiotic resistance data from 10 bacterial species and genera of clinical interest from our institution identified no deaths that were directly attributable to extremely drug-resistant bacteria. By comparing our observations to the 10 articles and reports studied herein, we concluded that their results lack empirical data. Interventions are urgently needed to significantly reduce both mortality and the healthcare costs associated with bacterial infections, including the implementation of local and national laboratory data-based surveillance systems for the routine surveillance of antibiotic resistance that would be helpful for a better understanding of how to manage antibiotic-resistant bacteria in the future.

Implementation and Initial Analysis of a Laboratory-Based Weekly Biosurveillance System, Provence-Alpes-Côte d'Azur, France.

We describe the implementation of an automated infectious disease surveillance system that uses data collected from 210 microbiologic laboratories throughout the Provence-Alpes-Côte d'Azur region in France. Each week, these facilities report bacterial species that have been isolated from patients in their area. An alarm is triggered whenever the case count for a bacterial species infection exceeds 2 SDs of the historical mean for that species at the participating laboratory. At its inception in July 2013, the system monitored 611 bacterial species. During July 1, 2013-March 20, 2016, weekly analyses of incoming surveillance data generated 34 alarms signaling possible infectious disease outbreaks; after investigation, 14 (41%) of these alarms resulted in health alerts declared by the regional health authority. We are currently improving the system by developing an Internet-based surveillance platform and extending our surveillance to include more laboratories in the region.

Why new antibiotics are not obviously useful now.

For several years, the threat of antibiotic resistance and its health cost has dramatically risen and various alarming figures have been proposed to illustrate the mortality due to antibiotic resistance. However, predictions concerning different living beings are doomed to failure, as theorised in Alice's 'living croquet' theory. Actors of antibiotic resistance are the doctors, the patient and the bacteria. Considering that animals and the environment are involved, future disasters are unpredictable. Here we evaluate in a rational manner the reliability of scientific sources showing increasing resistance to antibiotics or increasing mortality related to antibiotic resistance, and we finally consider antibiotic resources to face the situation.

Implementation of Syndromic Surveillance Systems in Two Rural Villages in Senegal.

Infectious diseases still represent a major challenge for humanity. In this context, their surveillance is critical. From 2010 to 2016, two Point-Of-Care (POC) laboratories have been successfully implemented in the rural Saloum region of Senegal. In parallel, a homemade syndromic surveillance system called EPIMIC was implemented to monitor infectious diseases using data produced by the POC laboratory of the Timone hospital in Marseille, France. The aim of this study is to describe the steps necessary for implementing EPIMIC using data routinely produced by two POC laboratories (POC-L) established in rural Senegal villages. After improving EPIMIC, we started to monitor the 15 pathogens routinely diagnosed in the two POC-L using the same methodology we used in France. In 5 years, 2,577 deduplicated patients-samples couples from 775 different patients have been tested in the Dielmo and Ndiop POC-L. 739 deduplicated patients-samples couples were found to be positive to at least one of the tested pathogens. The retrospective analysis of the Dielmo and Ndiop POC data with EPIMIC allowed to generate 443 alarms. Since January 2016, 316 deduplicated patients-samples couples collected from 298 different patients were processed in the Niakhar POC laboratory. 56 deduplicated patients-samples couples were found to be positive to at least one of the tested pathogens. The retrospective analysis of the data of the Niakhar POC laboratory with EPIMIC allowed to generate 14 alarms. Although some improvements are still needed, EPIMIC has been successfully spread using data routinely produced by two rural POC-L in Senegal, West Africa.

Identification of vancomycin-susceptible major clones of clinical Enterococcus from Algeria.

The main objectives of this study were to characterize clinical strains of Enterococcus spp. isolated from Algerian inpatients and outpatients, to investigate their susceptibility to antibiotics and to analyse their phylogenetic relatedness. A total of 85 non-duplicate Enterococcus spp. isolates collected between 2010 and 2013 from various clinical samples, including urine, vaginal swab, pus, blood and semen, from Algerian inpatients (n=62) and outpatients (n=23) were identified using matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/MS). Antibiotic susceptibility testing was performed using disk diffusion and Etest methods. Clonal relatedness was analysed using multilocus sequence typing (MLST). Enterococcus faecalis was the most predominant species (75.3%), followed by Enterococcus faecium (21.2%), Enterococcus gallinarum (2.4%) and Enterococcus casseliflavus (1.2%). High-level resistance to aminoglycosides was significantly more prevalent in hospitalized patients than in outpatients. None of the E. faecalis and E. faecium isolates were resistant to vancomycin. High genetic diversity was observed among the E. faecalis isolates, with the identification of a new clonal complex (CC256), as well as the detection of E. faecalis ST6 and E. faecium lineages ST17, ST18 and ST78 associated with hospital isolates. This is the first report of E. faecalis ST6 and E. faecium ST17 and ST18 in Algeria. Although acquired vancomycin resistance was not observed among the enterococcal strains, there is a continued need to monitor the level of antibiotic resistance among enterococci as well as the evolution of the E. faecalis/E. faecium ratio.

Enterococcus faecalis urinary-tract infections: Do they have a zoonotic origin?

Major human pathogens are frequently isolated from meat-producing animals, particularly poultry. Among them is Enterococcus faecalis, which is known to be one of the main cause of human urinary-tract infections worldwide. Early in 2015, we detected several, consecutive abnormal increases in the weekly number of human E. faecalis infections in various medical settings in the Provence-Alpes-Côte d'Azur region of France, especially including community-acquired urinary-tract infections. Speculating that this region-wide epidemiological event may have originated from animal-based food, we initiated this work to provide an overview of the epidemiology of E. faecalis, with a particular focus on the possible link between E. faecalis clones isolated from food-producing animals and those responsible for human urinary-tract infections. At that time, only one study had clearly identified strong epidemiological links between E. faecalis clones isolated from food-producing animals and human E. faecalis urinary-tract infections. This observation, coupled with our region-wide epidemiological experience, leads us to strongly believe that E. faecalis is a real zoonotic pathogen with potentially highly significant impact on human health. This is of particular concern because of its ability to acquire antibiotic-resistance genes and to infect animals and humans. Various strategies must be urgently implemented to address this public health threat, in particular through the development and implementation of large integrated automated surveillance systems based on animal and human health data to enable us to detect E. faecalis epidemiological events.

Decreasing level of resistance in invasive Klebsiella pneumoniae strains isolated in Marseille, January 2012-July 2015.

BACKGROUND: Klebsiella pneumoniae is a Gram-negative bacterial species well known for its capacity to cause infections in humans, and to carry and spread a wide variety of resistance genes including extended-spectrum beta-lactamase genes, carbapenem resistance genes, and colistin resistance genes. Recently, our real-time laboratory-based surveillance system MARSS (the Marseille Antibiotic Resistance Surveillance System) allowed us to observe a intringing dramatic decrease in the beta-lactam resistance level of the K. pneumoniae strains routinely isolated from patients hospitalized in our settings since 2013. Here we study the evolution of the prevalence of K. pneumoniae infections in Marseille university hospitals, France, from January 2012 to July 2015, and study their antibiotic resistance profiles. METHODS: We collected data referring to patients hostpitalized for K. pneumoniae infections in the 4 university hospitals of Marseille from January 2012 to July 2015. We then study their antibiotic resistance profiles according the clinical sites from which each strain was collected. Antibiotic consumption data from our four hospitals were also analyzed from January 2013 to July 2015. RESULTS: Overall, 4868 patients were admitted in our settings for K. pneumoniae infections over the study period. Overall, 40.1, 22.3, 25.6, 0.4, 29.9, 14.8, 27.3 and 37.0 % of the strains were resistant to amoxicillin plus clavulanic acid, piperacillin-tazobactam, ceftriaxone, imipenem, ciprofloxacin, gentamicin, trimethoprim-sulfamethoxazole and furan, respectively. 447 were invasive infections. The resistance level of our invasive strains was significantly lower than that presented by 11, 7, 10 and 11 other European countries included in the 2013 European Antimicrobial Resistance Surveillance Network report for ceftriaxone, imipenem, ciprofloxacin and gentamicin, respectively, but significantly higher than that of 13, 1, 17 and 13 European countries for the same antibiotics. We also observed that the percentages of resistance of our invasive strains to three of the four antibiotics decreased over the study. In parallel, antibiotic consumption remained stable in our four hospitals from January 2013 to July 2015. CONCLUSIONS: Altogether, our results underline that automated antibiotic-susceptibility testing results-based surveillance systems are crucial to better understand the evolving epidemiology of dangerous pathogenic bacterial species, like K. pneumoniae, at local scales.

Traditional and syndromic surveillance of infectious diseases and pathogens.

BACKGROUND: Infectious diseases remain a major public health problem worldwide. Hence, their surveillance is critical. Currently, many surveillance strategies and systems are in use around the world. An inventory of the data, surveillance strategies, and surveillance systems developed worldwide for the surveillance of infectious diseases is presented herein, with emphasis on the role of the microbiology laboratory in surveillance. METHODS: The data, strategies, and systems used around the world for the surveillance of infectious diseases and pathogens, along with current issues and trends, were reviewed. RESULTS: Twelve major classes of data were identified on the basis of their timing relative to infection, resources available, and type of surveillance. Two primary strategies were compared: disease-specific surveillance and syndromic surveillance. Finally, 262 systems implemented worldwide for the surveillance of infections were registered and briefly described, with a focus on those based on microbiological data from laboratories. CONCLUSIONS: There is currently a wealth of available data on infections, which has been growing with the recent emergence of new technologies. Concurrently with the expansion of computer resources and networks, these data will allow the optimization of real-time detection and notification of infections.