A. Le Monnier

Prevalence and pathogenicity of binary toxin–positive Clostridium difficile strains that do not produce toxins A and B

Clostridium difficile causes antibiotic-associated diarrhoea and pseudomembranous colitis. The main virulence factors of C. difficile are the toxins A (TcdA) and B (TcdB). A third toxin, called binary toxin (CDT), can be detected in 17% to 23% of strains, but its role in human disease has not been clearly defined. We report six independent cases of patients with diarrhoea suspected of having C. difficile infection due to strains from toxinotype XI/PCR ribotype 033 or 033-like, an unusual toxinotype/PCR ribotype positive for CDT but negative for TcdA and TcdB. Four patients were considered truly infected by clinicians and were specifically treated with oral metronidazole. One of the cases was identified during a prevalence study of A−B−CDT+ strains. In this study, we screened a French collection of 220 nontoxigenic strains and found only one (0.5%) toxinotype XI/PCR ribotype 033 or 033-like strain. The description of such strains raises the question of the role of binary toxin as a virulence factor and could have implications for laboratory diagnostics that currently rarely include testing for binary toxin.

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.

Article originalOptimisation de la prescription de la vancomycine : étude prospective observationnelle dans un centre hospitalo-universitaire parisienOptimized clinical use of vancomycin, a prospective observational study in a Paris teaching hospital

INTRODUCTION Vancomycin is still the cornerstone of antibiotic therapy for patients with suspected or proven invasive methicillin resistant Staphylococcus aureus infections. However, clinical and pharmacodynamic studies underline that appropriate doses depend on the infection site, the patients weight, his renal function, and the bacterial susceptibility. OBJECTIVE AND METHOD In this prospective study made in a Paris teaching hospital, our two goals were to describe the modalities of infusion and serum concentration obtained during therapy, in our pediatrics and adults population. RESULTS In our hospital, vancomycin was administered every eight hours in 83 % (97/102) of the cases and the doses used were 30 mg/kg per day in 67 % of cases (68/102). Serum trough levels reached 15 mcg/ml and 20 mcg/ml in 36 % and 18 % of cases respectively. Moreover, despite adequate doses, trough levels of 15 mcg/ml were obtained in only 40 % of cases. CONCLUSION Vancomycin infusion use could be optimized, by defining optimal serum concentrations and monitoring made by a mobile team of infectious diseases specialists.

Actualités épidémiologiques et thérapeutiques des infections à Clostridium difficile

During the past 10years, Clostridium difficile infections (CDI) have become a major public health challenge. Their epidemiology has changed with a rise in the number of cases and an increase in severe episodes. Recurrence and failure of conventional treatments have become more common. Furthermore, a spread of CDI has been observed in the general population-involving subjects without the usual risk factors (unexposed to antibiotic treatment, young people, pregnant women, etc.). All these change are partially due to the emergence of the hypervirulent and hyperepidemic clone NAP1/B1/027. New therapeutic strategies (antimicrobial treatment, immunoglobulins, toxin chelation, fecal microbiota transplantation) are now available and conventional treatments (metronidazole and vancomycin) have been reevaluated with new recommendations. Recent studies show a better efficacy of vancomycin compared to metronidazole for severe episodes. Fidaxomicin is a novel antibiotic drug with interesting features, including an efficacy not inferior to vancomycin and a lower risk of recurrence. Finally, for multi-recurrent forms, fecal microbiota transplantation seems to be the best option. We present the available data in this review.

Carriage of ESBL-producing Enterobacteriaceae in French hospitals: the PORTABLSE study

BACKGROUND Currently, contact precautions are recommended for patients colonized or infected with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). Recent studies have challenged this strategy. This study aimed to assess the rate of ESBL-PE faecal carriage among hospitalized patients according to type of hospital ward, and to identify risk factors associated with carriage. METHODS A point prevalence study was conducted in five different types of hospital ward [medical, surgical, intensive care unit (ICU), after care and rehabilitation, and geriatric] in eight French hospitals. All patients included in the study provided a fresh stool sample. RESULTS In total, 554 patients were included in the study, with a median age of 73 years (range 60-82 years). The overall faecal carriage rate of ESBL-PE was 17.7%. The most frequently encountered species among ESBL-PE was Escherichia coli (71.4%), followed by Klebsiella pneumoniae (14.3%). Risk factors associated with ESBL-PE faecal carriage on univariate analysis were: living in the Paris region (P<0.01) and hospitalization on a geriatric ward (P<0.01). Interestingly, the cumulative duration of hospital stay before screening was not associated with a significantly higher prevalence of ESBL-PE carriage, regardless of ward type. The ESBL-PE colonization rate was much higher for patients hospitalized on geriatric wards (28.1%) and ICUs (21.7%) compared with those for patients hospitalized on surgical wards (14.8%), medical wards (12.8%) or aftercare and rehabilitation (11.2%). CONCLUSION The overall prevalence of ESBL-PE faecal carriage was 17.7%, with only 21% of patients identified previously as carriers. The delay between admission and screening was not associated with an increase in ESBL-PE faecal carriage.

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.

Antibiotic strategy in severe community-acquired pneumococcal pneumonia

OBJECTIVE The authors had for aim to make an inventory of antibiotic treatment for severe community-acquired Streptococcus pneumoniae pneumonia and compare local practices to the local and national guidelines. PATIENTS AND METHOD An audit was conducted retrospectively in the Versailles hospital ICU between January 2006 and April 2009. Forty patients were included. RESULTS Ninety-three percent had major risk factors for pneumonia. Ninety-eight percent were treated, with the usual empirical treatment (69%) or treatment active against Pseudomonas aeruginosa (31%). Eighty-five percent of empirical treatment complied with the French national guidelines issued by the SPILF and 49% with the local ICU protocol, more restrictive for the choice of the agent and dose. Early de-escalation to amoxicillin was applied to 41% of patients after obtaining results for pneumococcal and Legionella antigen and results of respiratory sample direct examination. For all patients, empirical treatment was reassessed according to culture results: 81% were prescribed amoxicillin. Evaluation showed that 92% of treatment complied with SPILF guidelines and 65% with the local ICU protocol that required adaptation of amoxicillin doses according to MICs; adaptation to severity and BMI was necessary for ten patients. Mortality remained high, at 37%, despite using antibiotics still effective against S. pneumoniae. CONCLUSIONS This survey revealed a satisfactory adhesion to recommendations and prompt responsiveness of the team for adjustment of antibiotic therapy. The audit allowed updating the local ICU protocol.

Infective endocarditis: Clinical presentation, etiology, and early predictors of in-hospital case fatality.

OBJECTIVE We aimed to assess the clinical presentation, microbial etiology and outcome of patients presenting with infective endocarditis (IE). PATIENTS AND METHODS We conducted a four-year retrospective study including all patients presenting with IE. RESULTS We included 121 patients in the study. The median age was 74.8years. Most patients had native valve IE (57%). Staphylococcus aureus accounted for 24.8% of all IE. Surgery was indicated for 70 patients (57.9%) but actually performed in only 55 (44.7%). Factors associated with surgery were younger age (P=0.002) and prosthetic valve IE (P=0.001). Risk factors associated with in-hospital mortality were diabetes mellitus (OR=3.17), chronic renal insufficiency (OR=6.62), and surgical indication (OR=3.49). Mortality of patients who underwent surgery was one sixth of that of patients with surgical indication who did not have the surgery (P<0.001).