Novel scores relevant to antimicrobial resistance and hospital-acquired infections developed with data from a multi-hospital consortium in the Parisian region of France.

PURPOSE: Indicators for comparing and understanding differences in antimicrobial resistance (AMR) and healthcare-associated infections (HAIs) for benchmarking are essential to identify priorities for hospitals. METHODS: This study measured the incidence of hospital-acquired or resistant Gram-negative bacilli bloodstream infections (GNB-BSIs) in a large public healthcare consortium in the Parisian region of France. RESULTS: Within each hospital, there was a strong positive correlation between the incidence of GNB-BSIs due to resistant GNB and the incidence of hospital-acquired GNB-BSIs. Two scores measuring AMR and HAI rates by combining different GNB-BSI incidence rates were developed as indicators. These scores were highly variable within the hospital consortium. On multi-variate analysis, AMR and HAI scores were significantly associated with the proportion of surgical beds, staff absenteeism and the consumption of alcohol-based hand rub, with the latter two characteristics being amenable to interventions. Carbapenem use was also linked to AMR, but this may be because carbapenems are the preferred drug for treating resistant infections. CONCLUSION: These results shed light on the incidence of HAIs and AMR in the study hospitals, and suggest possibilities for targeted interventions at healthcare facility level.

[Impact of the first year of the COVID-19 pandemic on the epidemiology of invasive infections (bacteremia) in the hospitals of the Assistance Publique-Hôpitaux de Paris]. / Impact de la première année de la pandémie de COVID-19 sur l'épidémiologie des infections invasives (bactériémies) dans les hôpitaux de l'Assistance Publique­Hôpitaux de Paris.

Introduction: The COVID-19 pandemic has led to a massive influx of patients suffering from severe forms of the disease into hospitals, often requiring intensive care (vascular catheters, ventilation, etc.) which exposes them to high risks of nosocomial infections, particularly invasive infections (bacteremia). Method: The impact of the COVID-19 pandemic on the epidemiology of bacteremia in 2020 was analysed in 25 hospitals of the Assistance Publique-Hôpitaux de Paris (AP-HP, approximately 14,000 beds, covering the Île-de-France region). Up to a quarter of patients admitted to AP-HP during the March-April period (peak of the 1st wave) were infected with COVID-19. The incidence over 100 admissions of bacteraemia increased overall compared to previous years: by 24% in March 2020 and by 115% in April. Results: The evolution of the incidence of bacteremia was not the same for 2 groups of microorganisms with very different ecologies. For the "hospital" type microorganisms classically responsible for nosocomial infections, the incidence increased significantly in March-April 2020: Klebsiella pneumoniae (×2.3), Pseudomonas aeruginosa (×2.4), Staphylococcus aureus (×2.4), enterococci (×3.4), yeasts (×2.7). Two thirds of the bacteremias caused by these microorganisms were considered as acquired during hospitalization. Importantly, there was also a sharp increase in the incidence of bacteremia caused by antibiotic-resistant strains. The antibiotics used as indicators were the 3rd generation cephalosporins (3GCs), major antibiotics in the treatment of serious infections used for monitoring bacterial resistance in Europe. For example, the incidence of bacteremia with 3GC-resistant strains increased threefold in April 2020 for K. pneumoniae. During the same period, the consumption of 3GC increased sharply in the same hospitals (+131% in March and +148% in April). For Streptococcus pneumoniae (pneumococcus) and Streptococcus pyogenes (group A hemolytic streptococcus), two pathogens responsible for mainly community and respiratory-transmitted infections, the pandemic had the opposite effect. There was a decrease in incidence in 2020 by 34% and 28% respectively for these two species, particularly in the spring when strict containment, physical distancing and mask-wearing measures were in place. A slight re-emergence of infections with these two species occurred in the summer of 2020 after the relaxation of prevention measures. In contrast to what was seen above, 4/5 of the bacteremias caused by these two species were considered as community-acquired. Conclusion: The COVID-19 pandemic which had a strong impact on hospital management and social organization in the general population, had opposite impacts on the incidence of bacteremia depending on the pathogens and their mode of transmission.

Multidisciplinary advisory teams to manage multidrug-resistant tuberculosis: the example of the French Consilium.

SETTING: The World Health Organization (WHO) recommends that multidrug-resistant tuberculosis (MDR-TB) treatment should be managed in collaboration with multidisciplinary advisory committees (consilia). A formal national Consilium has been established in France since 2005 to provide a centralised advisory service for clinicians managing MDR-TB and extensively drug-resistant (XDR-TB) cases.OBJECTIVE: Review the activity of the French TB Consilium since its establishment.DESIGN: Retrospective description and analysis of the activity of the French TB Consilium.RESULTS: Between 2005 and 2016, 786 TB cases or contacts of TB cases were presented at the French TB Consilium, including respectively 42% and 79% of all the MDR-TB and XDR-TB cases notified in France during this period. Treatment regimens including bedaquiline and/or delamanid were recommended for 42% of the cases presented at the French TB Consilium since 2009. Patients were more likely to be presented at the French TB Consilium if they were born in the WHO Europe Region, had XDR-TB, were diagnosed in the Paris region, or had resistance to additional drugs than those defining XDR-TB.CONCLUSION: The French TB Consilium helped supervise appropriate management of MDR/XDR-TB cases and facilitated implementation of new drugs for MDR/XDR-TB treatment.

Prospective study on antimicrobial resistance in leprosy cases diagnosed in France from 2001 to 2015.

Antimicrobial resistance (AMR) in leprosy is mostly unknown because Mycobacterium leprae does not grow in vitro and bacteriologic investigations have been abandoned. However, molecular detection of resistance can be applied to multibacillary cases. Patients living in France mainland or in the French territories and diagnosed with leprosy from 2001 to 2015 were prospectively studied for AMR by detecting mutations in rpoB for rifampicin resistance, in folP1 for dapsone and in gyrA for ofloxacin. Single nucleotide polymorphism (SNP) genotypes 1-4 were determined for resistant strains. Of 334 skin biopsy samples received for suspicion of leprosy, 184 (55.1%) were positive for M. leprae (acid-fast bacilli and M. leprae-specific repetitive element PCR) corresponding to 160 multibacillary cases. AMR was detected in 18 cases (11.3%): 13 cases (8.1%) of dapsone resistance, three (1.9%) rifampicin and two (1.3%) ofloxacin. There were no strains with multidrug resistance. The mutations (numbering system of M. leprae TN strain genome) found were P55L (n = 7), T53I (n = 5), T53A (n = 1) in folP1; S456L (n = 2) and S456F (n = 1) in rpoB; and A91V (n = 2) in gyrA. Resistance proportion differ significantly between new and relapse cases (9/127, 7.0%, vs. 9/33, 25.7%, p 0.003). The frequency distribution of SNP1-4 types of resistant strains was two, one, 12 and three with five SNP3 cases from New Caledonia harbouring the same T53I FolP1 substitution. This is the first report of AMR surveillance for new and relapse cases of leprosy in Europe. Detection of resistance helped in individual treatment as well as in epidemiologic investigations.

Interpreting carbapenem susceptibility testing results for Pseudomonas aeruginosa.

OBJECTIVES: Carbapenems are among the most powerful antipseudomonal agents. Limited data is available on drug susceptibility testing by routine methods (disc diffusion and Etest) for meropenem and doripenem. We aimed to compare the in vitro activity of imipenem, meropenem, and doripenem against Pseudomonas aeruginosa. METHODS: A total of 311 P. aeruginosa strains isolated from respiratory specimens in 170 patients who developed ventilator-associated pneumonia in two intensive care units were collected over a period of 31 months. The susceptibility of these isolates to imipenem, meropenem, and doripenem were determined by Etest and disc diffusion method. RESULTS: Considering either all isolates or only the first isolates recovered per patient (311 and 170 respectively), the susceptibility rate for doripenem was higher than that for meropenem and imipenem. When MICs determined by Etest were converted into interpretative categories (S, I, R) using French (CA-SFM) guidelines, a poor correlation was observed for meropenem and doripenem. The percentages of correlation with the disc diffusion method were 90.6% and 89.7% for imipenem, 80.5% and 82.6% for meropenem, and 80.5% and 73.3% for doripenem, for the first isolates and all isolates, respectively. The rate of minor errors was as high as 17.7% and 16.1% for meropenem and 17.7% and 25.7% for doripenem for the first isolates and all isolates, respectively. CONCLUSION: The accuracy of disc diffusion using CA-SFM guidelines appears unsatisfactory for all three carbapenems justifying guideline update for P. aeruginosa and carbapenems.

Risk factors for extensive drug resistance in multidrug-resistant tuberculosis cases: a case-case study.

SETTINGS: Identification of extensively drug-resistant tuberculosis (XDR-TB) may be delayed because of the lack of availability of molecular testing for second-line drugs (SLDs). Early suspicion of XDR-TB is therefore necessary to avoid developing further drug resistance. OBJECTIVE: To identify the characteristics associated with XDR-TB among multidrug-resistant TB (MDR-TB) cases before the availability of second-line drug susceptibility testing (DST) results. METHODS: All MDR-TB cases with available second-line DST results recorded in France from 1998 to 2013 were classified as simple MDR-TB (no resistance to fluoroquinolones [FQs] or second-line injectable drugs [SLIDs]), pre-XDR-TB (resistance to FQs or SLIDs) and XDR-TB cases (resistance to both). RESULTS: A total of 833 MDR-TB cases were analysed, including 168 (20%) pre-XDR and 62 (7%) XDR-TB cases. A previous history of treatment was acknowledged among 41% of the cases; 12% were human immunodeficiency virus-positive. Characteristics independently associated with XDR-TB were foreign birth (OR 9.5), previous anti-tuberculosis treatment (OR 2.6), smear positivity (OR 4.5) and ethambutol (EMB) resistance (OR 9.1). Characteristics independently associated with pre-XDR-TB compared to simple MDR-TB cases were male sex (OR 1.6), birth in Europe (OR 2.6) and EMB resistance (OR 1.9). CONCLUSION: The presence of clinical or bacteriological characteristics associated with XDR-TB should lead to rapid molecular testing for resistance to SLDs before starting tailored treatment.

Multidrug and extensively drug-resistant tuberculosis.

The emergence of drug-resistant tuberculosis (TB) compromises global tuberculosis control. The incidence of multidrug-resistant strains (MDR) defined as resistant to the two main antituberculosis drugs, rifampicin and isoniazid, was raised in the 1990s. Ten percent of these strains have developed additional resistance to the main second-line antituberculosis drugs: fluoroquinolones and aminoglycosides. These strains are defined as extensively drug-resistant (XDR). The prognosis of MDR-TB and XDR-TB is poor due to limited therapeutic resources. However, many new innovations may lead to a radical change in this field. Genotypic testing is now able to detect drug resistance within a few hours. Genotypic diagnosis of rifampicin resistance is now recommended in France for each new case of TB. The currently recommended treatment for MDR-TB is long (18-24 months) and toxic. It is, however, on the verge of being replaced by a 9-month treatment. New antituberculosis drugs such as bedaquiline and delamanid should also improve the prognosis of MDR-TB and XDR-TB.

Estimating the morbidity and mortality associated with infections due to multidrug-resistant bacteria (MDRB), France, 2012.

BACKGROUND: A study based on 2007 data estimated that 386,000 infections due to multidrug-resistant bacteria (MDRB) occurred in Europe that year and 25,000 patients died from these infections. Our objective was to estimate the morbidity and mortality associated with these infections in France. METHODS: The MDRB considered were methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide-resistant enterococci, third-generation cephalosporin-resistant (3GC-R) Escherichia coli and Klebsiella pneumoniae, carbapenem-resistant Klebsiella pneumoniae, Acinetobacter spp. and Pseudomonas aeruginosa (CR P. aeruginosa). The number of invasive infections (infections with bacteria isolated from blood or cerebrospinal fluid) due to MDRB, as reported by France to EARS-Net in 2012, was corrected for the coverage of our surveillance network and extrapolated to other body sites using ratios from the French healthcare-associated infections point prevalence survey and the literature. Mortality associated with MDRB infection was estimated using proportions from the literature. Methods and parameters were reviewed by a panel of experts. RESULTS: We estimate that 158,000 (127,000 to 245,000) infections due to MDRB occurred in 2012 in France (incidence: 1.48 to 2.85 per 1000 hospital days), including 16,000 invasive infections. MRSA, 3GC-R E. coli and K. pneumoniae were responsible for 120,000 (90,000 to 172,000) infections, i.e., 75% of the total. An estimated 12,500 (11,500 to 17,500) deaths were associated with these infections, including 2,700 associated with invasive infections. MRSA, 3GC-R E. coli and CR P. aeruginosa accounted for 88% of these deaths. CONCLUSION: These first estimates confirm that MRSA, 3GC-R Escherichia coli and Klebsiella pneumoniae account for the largest portion of the morbidity and mortality of infections due to MDRB in France. These results are not directly comparable with the European study because the methodology used differs in many respects. The differences identified between our study and previous studies underline the need to define a standardised protocol for international assessments of the morbidity and mortality of antibiotic resistance. Estimating morbidity and mortality will facilitate communication and awareness in order to reinforce adherence and support of healthcare professionals and policy-makers to MDRB prevention programs.

Evaluation of excreta management in a large French multi-hospital institution.

BACKGROUND: Excreta are a major source of multidrug-resistant Enterobacteriaceae including strains that produce extended-spectrum beta-lactamase (ESBL). The increase of ESBL incidence in Assistance Publique - Hôpitaux de Paris (AP-HP) hospitals prompted an evaluation of the equipment and practices used to dispose of excreta. AIM: To evaluate the use of equipment for the management of excreta and to review practices of healthcare workers in their disposal. METHODS: A cross-sectional survey was conducted in 2012. FINDINGS: A total of 28 AP-HP hospitals including 536 units (342 acute care units and 194 rehabilitation and long-term care units) were evaluated. Among the patients on the day of the survey, 5697 (43%) wore diapers and 1767 (13%) were using a bedpan. Sixty-one percent of the beds were equipped with shared toilets and 43% of the toilets were equipped with hand sprayers, a device favouring the spread of faecal material in the environment. Sixty eight percent of the units were equipped with bedpan washer-disinfectors. Only 52% of the bedpan washer-disinfectors were located in rooms where alcohol-based hand rubs (ABHRs) were available. In 71% of the units the bedpan was rinsed before disinfection, mostly in the patient's bathroom (62%). Finally, only 9% of questioned healthcare workers said they followed an educational programme about excreta disposal. CONCLUSION: This survey shows that, in the field of multidrug-resistant Enterobacteriaceae control and the promotion of hand hygiene with ABHRs, excreta management is a concerning but neglected subject.

French recommendations for the prevention of 'emerging extensively drug-resistant bacteria' (eXDR) cross-transmission.

Controlling the spread of multi- or extensively drug-resistant bacteria (MDR or XDR) includes a dual strategy for reducing antibiotic prescriptions and preventing their spread from patient carriers. Standard precautions are applicable to all health professionals caring for any patients; additional barrier precautions (isolation) are recommended for patients carrying transmissible infectious diseases or MDR bacteria in sporadic or epidemic situations. Moreover, additional precautions may be required for populations at particular risk of infection or colonization by emerging XDR (eXDR), defined in our country as carbapenemase-producing Enterobacteriaceae and vancomycin-resistant enterococci. Our ability to detect and identify eXDR carriers early and ensure their follow-up, through effective communication between all those involved, is a significant challenge for controlling their spread. Thus, the French High Committee for Public Health has updated and standardized all French existing recommendations concerning the prevention of the cross-transmission of these bacteria, and these recommendations are summarized in this review. The recommendations are based on scientific and operational knowledge up to 2013. Different preventive strategies are recommended for patients found to be carrying eXDR and those who are considered to be at risk of having eXDR because of a history of contact. The local context, the experience of the infection control team, the different times at which detection of eXDR takes place (during admission, hospitalization, etc.) and the epidemiological situation (sporadic cases, clusters, outbreaks, widespread epidemic) must be included in risk assessments that in turn inform the control measures that should be applied in each clinical circumstance.

Spontaneous ascitic fluid infection and bacteremia due to Yersinia pseudotuberculosis in a liver transplant patient.

We report herein a case of bacteremic ascitic fluid infection in a liver transplant patient caused by a strain of Yersinia pseudotuberculosis serogroup I that lost the yersiniabactin core. The patient's outcome was favorable after a combined therapy with a third-generation cephalosporin and gentamicin.

Impact of the BCG vaccination policy on tuberculous meningitis in children under 6 years in metropolitan France between 2000 and 2011.

In France, Bacillus Calmette­Guérin (BCG) vaccination by multipuncture device was withdrawn in 2006. In 2007, universal mandatory BCG vaccination was replaced by vaccination of high-risk children. To evaluate the impact of these changes on tuberculous meningitis (TBM) epidemiology, data on culture-positive and culture-negative (or unknown microbiological result) TBM in ≤5 years olds were collected from 2000­2011. Ten culture-positive and 17 culture-negative TBM cases were identified, with an annual incidence rate ranging from 0.16 to 0.66 cases per 10 million inhabitants. The average annual numbers of TBM cases were 2.7 and 1.8 from 2000­2005 and 2006­2011, respectively. In Ile-de-France where all children are considered at risk, the overall incidence rates were 1.14 and 0.29 per million for the two periods. In other regions where only at-risk children are vaccinated since 2007, rates were 0.30 and 0.47, respectively. None of these differences were significant. Annual incidence rates for each one year age group cohort were comparable before and after changes. Childhood TBM remains rare in France. No increase in incidence was observed after changes in BCG vaccination strategy. Ongoing surveillance should be maintained, as a slight increase in TBM in the coming years remains possible, in the context of suboptimal vaccination coverage of high-risk children.

[Carbapenemase-producing enterobacteriae: epidemiology, strategies to control their spread and issues]. / Maîtrise de la diffusion des entérobactéries productrices de carbapénémases : épidémiologie, stratégies de prévention et enjeux.

The increasing bacterial resistance to antibiotics has become a major public health concern bringing the threat of therapeutic impasses. In this context, control of the spread of highly-resistant bacteria emerging antibiotics (BHRe), such as glycopeptide-resistant enterococci (VRE) and Enterobacteriaceae producing carbapenemases (CPE), is based on a dual strategy of reducing the prescription of antibiotics to limit the pressure selection and preventing the spread from carriers. Prevention strategy is based on three different levels such as standard precautions for all patients with a particular focus on the management of excreta, and additional precautions for BHRe carriers. What makes it difficult is that carriage is usually completely asymptomatic, enterobacteria and enterococci are normal commensal of gut microbiota. Explosive dissemination of Enterobacteriaceae producing extended spectrum beta-lactamases in hospital and community heralds the emergence of CPE whose import by patients with a history of hospitalization in abroad may be the main source of spread in France.

Comparison of a semiautomated commercial repetitive-sequence-based PCR method with spoligotyping, 24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat typing, and restriction fragment length polymorphism-based analysis of IS6110 for Mycobacterium tuberculosis typing.

Fifty-two multidrug-resistant isolates of Mycobacterium tuberculosis representative of the currently predominant lineages in France were analyzed using repetitive-sequence-based PCR (rep-PCR) DiversiLab (DL), spoligotyping, 24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat typing (MIRU-VNTR), and restriction fragment length polymorphism of IS6110 (IS6110-RFLP). DL, as opposed to MIRU-VNTR and IS6110-RFLP analysis, did not allow discrimination among half of the isolates, an indication of comparatively lower resolving power.

Ruling out false-positive urinary Legionella pneumophila serogroup 1 and Streptococcus pneumoniae antigen test results by heating urine.

We report here false-positive urinary Legionella pneumophila serogroup 1 and Streptococcus pneumoniae antigen test results due to rabbit antilymphocyte serum treatment and provide a simple and fast solution to rule them out by heating urine.