Vincent Fihman

Hospital cost of Clostridium difficile infection including the contribution of recurrences in French acute-care hospitals

BACKGROUND The impact of Clostridium difficile infection (CDI) on healthcare costs is significant due to the extra costs of associated inpatient care. However, the specific contribution of recurrences has rarely been studied. AIM The aim of this study was to estimate the hospital costs of CDI and the fraction attributable to recurrences in French acute-care hospitals. METHODS A retrospective study was performed for 2011 on a sample of 12 large acute-care hospitals. CDI costs were estimated from both hospital and public insurance perspectives. For each stay, CDI additional costs were estimated by comparison to controls without CDI extracted from the national DRG (diagnosis-related group) database and matched on DRG, age and sex. When CDI was the primary diagnosis, the full cost of stay was used. FINDINGS A total of 1067 bacteriological cases of CDI were identified corresponding to 979 stays involving 906 different patients. Recurrence(s) were identified in 118 (12%) of these stays with 51.7% of them having occurred within the same stay as the index episode. Their mean length of stay was 63.8 days compared to 25.1 days for stays with an index case only. The mean extra cost per stay with CDI was estimated at €9,575 (median: €7,514). The extra cost of CDI in public acute-care hospitals was extrapolated to €163.1 million at the national level, of which 12.5% was attributable to recurrences. CONCLUSION The economic burden of CDI is substantial and directly impacts healthcare systems in France.

Cervical necrotizing fasciitis: 8-years’ experience of microbiology

Cervical necrotizing fasciitis (CNF) is a life-threatening complication of pharyngeal or dental infections. The aim of this paper was to investigate whether dental or pharyngeal source result from different pathogen(s) in CNF and whether antibiotics, given before admission, influence the antimicrobial resistance of pathogens. In 152 CNF patients, Streptococcus milleri group and Prevotella species were the predominant isolates, frequently copathogens, mostly in dental CNF samples. Penicillin and clindamycin resistance were observed in 39% and 37% of cases, respectively, independently of any previous antibiotic therapy. Thus, a combined aerobe–anaerobe infection may have a synergistic effect, which allows the infection to spread in cervical tissues.

Five-year trends for ventilator-associated pneumonia: Correlation between microbiological findings and antimicrobial drug consumption.

The epidemiology of multidrug-resistant bacteria (MDRB) has changed significantly in European healthcare settings, with a decrease in frequency of meticillin-resistant Staphylococcus aureus and an increase in extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. Little is known about the effects of these changes on ventilator-associated pneumonia (VAP). A retrospective 5-year trend analysis of ICU antibiotic consumption and resistance in bacteria causing VAP was undertaken. Poisson regression analysis between complete microbiological data and antibiotic consumption was performed. In total, 252 episodes of VAP in 184 patients were identified between 2007 and 2011, from which 364 causal bacteria were isolated. Enterobacteriaceae isolation rates increased significantly over this period [from 6.64 to 10.52 isolates/1000 patient-days; P=0.006], mostly due to an increase in AmpC-producing Enterobacteriaceae (APE) (2.85-4.51 isolates/1000 patient-days; P=0.013), whereas the number of episodes due to S. aureus and Pseudomonas aeruginosa remained stable. A positive association was found between the increase in APE infections and an increase in past-year antibiotic consumption: amoxicillin/clavulanic acid (P=0.003), ceftazidime and cefepime (P=0.007), carbapenems (P=0.002), fluoroquinolones (P=0.012), macrolides (P=0.002) and imidazoles (P=0.004). No such association was found for the emergence of resistance in P. aeruginosa. These results indicate a change in the epidemiology of VAP, with Enterobacteriaceae exceeding P. aeruginosa and S. aureus. Moreover, a positive correlation was observed between antibiotic consumption and the incidence of potentially MDRB such as APE. No such correlation was found for ESBL-producing Escherichia coli and antibiotic-resistant P. aeruginosa.

Costs associated with implementation of a strict policy for controlling spread of highly resistant microorganisms in France

Objective To assess costs associated with implementation of a strict ‘search and isolate’ strategy for controlling highly drug-resistant organisms (HDRO). Design Review of data from 2-year prospective surveillance (01/2012 to 12/2013) of HDRO. Setting Three university hospitals located in northern Paris. Methods Episodes were defined as single cases or outbreaks of glycopeptide-resistant enterococci (GRE) or carbapenemase-producing Enterobacteriacae (CPE) colonisation. Costs were related to staff reinforcement, costs of screening cultures, contact precautions and interruption of new admissions. Univariate analysis, along with simple and multiple linear regression analyses, was conducted to determine variables associated with cost of HDRO management. Results Overall, 41 consecutive episodes were included, 28 single cases and 13 outbreaks. The cost (mean±SD) associated with management of a single case identified within and/or 48 h after admission was €4443±11 552 and €11 445±15 743, respectively (p<0.01). In an outbreak, the total cost varied from €14 864 ±17 734 for an episode with one secondary case (€7432±8867 per case) to €136 525 ±151 231 (€12 845±5129 per case) when more than one secondary case occurred. In episodes of single cases, contact precautions and microbiological analyses represented 51% and 30% of overall cost, respectively. In outbreaks, cost related to interruption of new admissions represented 77–94% of total costs, and had the greatest financial impact (R2=0.98, p<0.01). Conclusions In HDRO episodes occurring at three university hospitals, interruption of new admissions constituted the most costly measure in an outbreak situation.

Distribution and antimicrobial susceptibility of bacteria from adults with community-acquired pneumonia or complicated skin and soft tissue infections in France: the nationwide French PREMIUM study.

The empirical therapy of community-acquired pneumonia (CAP) and complicated skin and soft tissue infections (cSSTIs) must be based on updated bacterial distribution and susceptibility data. A nationwide study consecutively collected 1288 isolates from CAP (n=467) and cSSTIs (n=821) from 18 French hospitals between 2012 and 2013. The MIC values of commonly used antimicrobial agents, including ceftaroline, were determined. Bacterial distribution featured Pneumococcus, Haemophilus influenzae, and Staphylococcus aureus for CAPs and S. aureus, β-hemolytic streptococci and Enterobacteriaceae for cSSTIs. Antimicrobial susceptibility testing indicated i) the sustained third-generation cephalosporins and levofloxacin activity against pneumococci and H. influenzae, ii) no methicillin-resistant Staphylococcus aureus emergence among respiratory pathogens, iii) the high in vitro activity of ceftaroline against staphylococci from cSSTIs (98.7% susceptibility), and iv) the worrisome decreasing fluoroquinolone and third-generation cephalosporin susceptibilities among Enterobacteriaceae. This laboratory-based survey depicts a contrasting situation and supports the scoring of patients for the resistant pathogen risk before empirical therapy.

Decreased susceptibility to chlorhexidine affects a quarter of Escherichia coli isolates responsible for pneumonia in ICU patients

Béatrice La Combe, Alexandre Bleibtreu, Jonathan Messika, Romain Fernandes, Olivier Clermont, Catherine Branger, Typhaine Billard‐Pomares, Guilène Barnaud, Fatma Magdoud, Matthieu Eveillard, Achille Kouatchet, Sigismond Lasocki, Pierre Asfar, Stéphane Corvec, Karim Lakhal, Laurence Armand‐Lefevre, Michel Wolff, Jean‐François Timsit, Sandrine Bourdon, Jean Reignier, Stéphanie Martin, Vincent Fihman, Nicolas de Prost, Julien Bador, Pierre‐Emmanuel Charles, Julien Goret, Alexandre Boyer, Frederic Wallet, Emmanuelle Jaillette, Saad Nseir, Luce Landraud, Raymond Ruimy, Pierre‐Eric Danin, Jean Dellamonica, Julie Cremniter, Jean‐Pierre Frat, Françoise Jauréguy, Christophe Clec’h, Dominique Decré, Eric Maury, Didier Dreyfuss, Erick Denamur and Jean‐Damien Ricard

Characteristics of Aspergillus fumigatus in Association with Stenotrophomonas maltophilia in an In Vitro Model of Mixed Biofilm.

Background Biofilms are communal structures of microorganisms that have long been associated with a variety of persistent infections poorly responding to conventional antibiotic or antifungal therapy. Aspergillus fumigatus fungus and Stenotrophomonas maltophilia bacteria are examples of the microorganisms that can coexist to form a biofilm especially in the respiratory tract of immunocompromised patients or cystic fibrosis patients. The aim of the present study was to develop and assess an in vitro model of a mixed biofilm associating S. maltophilia and A. fumigatus by using analytical and quantitative approaches. Materials and Methods An A. fumigatus strain (ATCC 13073) expressing a Green Fluorescent Protein (GFP) and an S. maltophilia strain (ATCC 13637) were used. Fungal and bacterial inocula (105 conidia/mL and 106 cells/mL, respectively) were simultaneously deposited to initiate the development of an in vitro mixed biofilm on polystyrene supports at 37°C for 24 h. The structure of the biofilm was analysed via qualitative microscopic techniques like scanning electron and transmission electron microscopy, and fluorescence microscopy, and by quantitative techniques including qPCR and crystal violet staining. Results Analytic methods revealed typical structures of biofilm with production of an extracellular matrix (ECM) enclosing fungal hyphae and bacteria. Quantitative methods showed a decrease of A. fumigatus growth and ECM production in the mixed biofilm with antibiosis effect of the bacteria on the fungi seen as abortive hyphae, limited hyphal growth, fewer conidia, and thicker fungal cell walls. Conclusion For the first time, a mixed A. fumigatus—S. maltophilia biofilm was validated by various analytical and quantitative approaches and the bacterial antibiosis effect on the fungus was demonstrated. The mixed biofilm model is an interesting experimentation field to evaluate efficiency of antimicrobial agents and to analyse the interactions between the biofilm and the airways epithelium.

Gram-negative bacteremia: Which empirical antibiotic therapy? ☆

PURPOSE Given the increasing frequency of cefotaxime-resistant strains, third-generation cephalosporins (3GC e.g. cefotaxime, ceftriaxone) might not be recommended any longer as empirical antibiotic therapy for community-acquired Gram-negative bacteremia (CA-GNB). PATIENTS AND METHODS We conducted a multicenter prospective descriptive study including patients with CA-GNB. RESULTS Two hundred and nineteen patients were included. Escherichia coli and Pseudomonas aeruginosa were the most frequently isolated species in 63% (n=138) and 11% (n=24) of the cases, respectively. The prevalence of cefotaxime-resistance reached 18% (n=39) mostly due to intrinsic resistance (27 cases, 12%). The presence of invasive material (P<0.001), the origin of the patient (Paris region or West of France) (P=0.006), and home health care (P<0.001) were variables predicting resistant GNB. The negative predictive value for resistance in patients with invasive material coming from the West of France, or without invasive material and with home health care was 94%. The positive predictive value for patients with invasive material living in Paris, or without invasive material and with home health care only reached 58 and 54%, respectively. CONCLUSIONS Using 3GC for CA-GNB due to cefotaxime-resistant strains was relatively frequent, ESBL-producing Enterobacteriaceae being rarely involved. Our study highlights the role of local epidemiology; before any changes to first-line antibiotic therapy, local epidemiological data should be taken into account.

Are bacterial culture quantifications reliable? Comparative performance of the WASP automated inoculation instrument in the era of ISO 15189 accreditation

Purpose. Isolating colonies and obtaining accurate colony counts from bacterial cultures are critical steps for the optimal management of infected patients. The uncertainties in the colony count results from the bacterial cultures were evaluated by verifying the performance of the WASP inoculation system according to the International Organization for Standardization (ISO) 15189 standard. Methodology. We first (i) evaluated the cross‐contamination and precision of the WASP instrument (Copan Diagnostics, Italy) and (ii) established enumeration reading grids for urine, swab, bronchopulmonary specimens (BPSs) and catheter tip cultures. Subsequently, 72 clinical samples were tested to compare the results of the WASP, PREVI Isola (bioMérieux, France) and manual inoculation methods. Results. The WASP method did not show cross‐contamination. The coefficient of variation for the colony counts in the repeatability experiment was evaluated for 10 &mgr;l and 30 &mgr;l loop protocols and determined to be 29 and 14 %, respectively. The agreement between the automated and manual methods and between the automated methods for the colony counts was high (94.4 and 100 %, respectively). The WASP method yielded better isolation quality compared to the manual method (P=0.020) and to the PREVI Isola only when polymicrobial specimens were considered (P=0.014). For quantification evaluation, the measurement uncertainty was evaluated to 1.8×103 c.f.u. ml‐1 for a suspension of Escherichia coli at 104 c.f.u. ml‐1. Conclusion. We report the verification of the performance of the WASP instrument and describe a rapid procedure for achieving semi‐quantitative cultures from BPSs and catheter tips. Quantitative interpretation of the bacterial cultures should be performed with caution.

Use of Andromas and Bruker MALDI-TOF MS in the identification of Neisseria

Through the past decade, MALDI-TOF MS has been recognized as a fast and robust tool for identification of most bacteria in clinical microbiology. However, the accuracy of this method to identify Neisseria species is still debated, and few data are available about commensal Neisseria species identification. In this study, we assessed two MALDI-TOF MS systems (Bruker Biotyper and Andromas) for the identification of 88, 18, and 29 isolates of Neisseria gonorrhoeae, Neisseria meningitidis, and commensal Neisseria species, respectively. All 88 isolates of N. gonorrhoeae were correctly identified using both systems, and most N. meningitidis and commensal Neisseria species were well identified: only 1/18 isolates of N. meningitidis was misidentified using Bruker Biotyper, and 1 isolate of Neisseria polysaccharea was misidentified as N. meningitidis using both systems. These results strengthen the possibility to use MALDI-TOF MS as a single method for Neisseria identification in routine, with excellent performance for N. gonorrhoeae identification. However, results should be interpreted prudently for N. meningitdis and commensal Neisseria species when isolated from genital and oropharyngeal samples where these both species can coexist.