Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency.

Herpes simplex virus (HSV) infections are very common in the general population and among immunocompromised patients. Acyclovir (ACV) is an effective treatment which is widely used. We deemed it essential to conduct a wide and coordinated survey of the emergence of ACV-resistant HSV strains . We have formed a network of 15 virology laboratories which have isolated and identified, between May 1999 and April 2002, HSV type 1 (HSV-1) and HSV-2 strains among hospitalized subjects. The sensitivity of each isolate to ACV was evaluated by a colorimetric test (C. Danve, F. Morfin, D. Thouvenot, and M. Aymard, J. Virol. Methods 105:207-217, 2002). During this study, 3,900 isolated strains among 3,357 patients were collected; 55% of the patients were immunocompetent. Only six immunocompetent patients excreted ACV-resistant HSV strains (0.32%), including one female patient not treated with ACV who was infected primary by an ACV-resistant strain. Among the 54 immunocompromised patients from whom ACV-resistant HSV strains were isolated (3.5%), the bone marrow transplantation patients showed the highest prevalence of resistance (10.9%), whereas among patients infected by human immunodeficiency virus, the prevalence was 4.2%. In 38% of the cases, the patients who excreted the ACV-resistant strains were treated with foscarnet (PFA), and 61% of them developed resistance to PFA. The collection of a large number of isolates enabled an evaluation of the prevalence of resistance of HSV strains to antiviral drugs to be made. This prevalence has remained stable over the last 10 years, as much among immunocompetent patients as among immunocompromised patients.Herpes simplex virus (HSV) infections are very common; they are localized on the face and torso in the case of HSV type 1 (HSV-1) and in the genital region in the case of HSV-2. HSV-1 infections in the genital region are on the increase (40). Ocular herpes is less frequent, and neonatal herpes and herpetic meningoencephalitis are very rare but have a severe functional and vital prognosis (37).Since acyclovir (ACV) {9-[(2-hydroxyethoxy)methyl)guanine]} was introduced to the market in 1983, it has been used primarily in the prevention and treatment of HSV infections. ACV-resistant HSV strains have been observed in vivo since the first large therapeutic trials (5, 10, 36). These resistant strains are detected in vitro by phenotypic tests which determine the antiviral concentration inhibiting viral replication by 50%. Several methods have been used to evaluate the sensitivity of the HSV strains to ACV, including techniques to detect the intensity of the cytopathic effect, such as the plaque reduction (17, 31) and colorimetric (11,22,26) techniques, but also the detection of DNA replication by hybridization (39) or antigen production by flow cytometry (30).Previous surveys among immunocompetent patients have shown a prevalence of resistance to ACV varying between 0 and 0.6%, whereas among immunocompromised patients, the prevalence varied between 3 and 6% (9,16,29). The use of ACV is co...

BackgroundCurrent recommendations for empirical antimicrobial therapy in spontaneous bacterial peritonitis (SBP) are based on quite old trials. Since microbial epidemiology and the management of patients have changed, whether these recommendations are still appropriate must be confirmed.MethodsAn observational study that exhaustively collected the clinical and biological data associated with positive ascitic fluid cultures was conducted in four French university hospitals in 2010–2011.ResultsTwo hundred and sixty-eight documented positive cultures were observed in 190 cirrhotic patients (median age 61.5 years, 58.5% Child score C). Of these, 57 were classified as confirmed SBP and 140 as confirmed bacterascites. The predominant flora was Gram-positive cocci, whatever the situation (SBP, bacterascites, nosocomial/health-care related or not). Enteroccocci (27.7% E. faecium) were isolated in 24% of the episodes, and in 48% from patients receiving quinolone prophylaxis. E. coli were susceptible to amoxicillin-clavulanate and to third-generation cephalosporins in 62.5% and 89.5% of cases, respectively. No single antibiotic allowed antimicrobial coverage of more than 60%. Only combinations such as amoxicillin + third-generation cephalosporin or cotrimoxazole allowed coverage close to 75-80% in non-nosocomial episodes. Combinations based on broader spectrum antibiotics should be considered for empirical therapy of nosocomial infections.ConclusionsOur study confirmed the changing spectrum of pathogens in SBP and bacterascites, and the need for more complex antibiotic strategies than those previously recommended. Our findings also underline the need for new clinical trials conducted in the current epidemiological context.

S. Tubiana). y Bruno Hoen and Xavier Duval contributed equally. z The members of COMBAT study group are listed at the Acknowledgments section. Contents lists available at ScienceDirect Clinical Microbiology and Infectionj o u r n a l h o m e p a g e : w w w . c l i n i c a l m i c r o b i o l o g y a n d i n f e c t i o n . c o m

The bacterial epidemiology of bacterascites and spontaneous bacterial peritonitis is evolving. Four hundred and eleven strains isolated from ascites in cirrhotic patients from 5 French hospitals were isolated in 2006 and 2007. Of these, 114 were definitely associated with spontaneous bacterial peritonitis. The proportion of Gram-positive and Gram-negative agents was quite similar, even after excluding coagulase-negative staphylococci, or when considering only definite spontaneous bacterial peritonitis or community-acquired strains. Staphylococci and Escherichia coli were the most frequent pathogens, but enterococci were also involved in nearly 15% of the cases. Among the E. coli, 28% were intermediate or resistant to amoxicillin+clavulanate, 5.3% expressed cephalosporinases or extended beta-lactamases and 17.3% were intermediate or resistant to fluoroquinolones. Resistance to methicillin was observed in 27% of Staphylococcus aureus. Cefotaxime and amoxicillin-clavulanate remained the most effective 'single' agents, however on less than 70% of isolates. Some combinations (such as cefotaxime+amoxicillin) extended coverage to a further 15% of strains. Since inadequate empiric antibiotic therapy is associated with increased mortality, these combinations may be of great interest as first-line treatment, even though they may also lead to the development of antimicrobial resistance. Repeated epidemiological surveys and new clinical trials are thus needed.