Hervé Richet

SHEA Guideline for Preventing Nosocomial Transmission of Multidrug-Resistant Strains of Staphylococcus aureus and Enterococcus

patients with MRSA or VRE usually acquire it via spread. The CDC has long-recommended contact precautions for patients colonized or infected with such pathogens. Most facilities have required this as policy, but have not actively identified colonized patients with sur veillance cultures, leaving most colonized patients undetected and unisolated. Many studies have shown control of endemic and/or epidemic MRSA and VRE infections using surveillance cultures and contact precautions, demonstrating consistency of evidence, high strength of association, reversibility, a dose gradient, and specificity for control with this approach. Adjunctive control measures are also discussed. CONCLUSION: Active surveillance cultures are essential to identify the reservoir for spread of MRSA and VRE infections and make control possible using the CDC’s long-recommended contact precautions (Infect Control Hosp Epidemiol 2003;24:362-386).

Comparative Genomics of Multidrug Resistance in Acinetobacter baumannii

Acinetobacter baumannii is a species of nonfermentative gram-negative bacteria commonly found in water and soil. This organism was susceptible to most antibiotics in the 1970s. It has now become a major cause of hospital-acquired infections worldwide due to its remarkable propensity to rapidly acquire resistance determinants to a wide range of antibacterial agents. Here we use a comparative genomic approach to identify the complete repertoire of resistance genes exhibited by the multidrug-resistant A. baumannii strain AYE, which is epidemic in France, as well as to investigate the mechanisms of their acquisition by comparison with the fully susceptible A. baumannii strain SDF, which is associated with human body lice. The assembly of the whole shotgun genome sequences of the strains AYE and SDF gave an estimated size of 3.9 and 3.2 Mb, respectively. A. baumannii strain AYE exhibits an 86-kb genomic region termed a resistance island—the largest identified to date—in which 45 resistance genes are clustered. At the homologous location, the SDF strain exhibits a 20 kb-genomic island flanked by transposases but devoid of resistance markers. Such a switching genomic structure might be a hotspot that could explain the rapid acquisition of resistance markers under antimicrobial pressure. Sequence similarity and phylogenetic analyses confirm that most of the resistance genes found in the A. baumannii strain AYE have been recently acquired from bacteria of the genera Pseudomonas, Salmonella, or Escherichia. This study also resulted in the discovery of 19 new putative resistance genes. Whole-genome sequencing appears to be a fast and efficient approach to the exhaustive identification of resistance genes in epidemic infectious agents of clinical significance.

The Epidemiology and Control of Acinetobacter baumannii in Health Care Facilities

Acinetobacter baumannii is a ubiquitous pathogen capable of causing both community and health care-associated infections (HAIs), although HAIs are the most common form. This organism has emerged recently as a major cause of HAI because of the extent of its antimicrobial resistance and its propensity to cause large, often multifacility, nosocomial outbreaks. The occurrence of outbreak is facilitated by both tolerance to desiccation and multidrug resistance, contributing to the maintenance of these organisms in the hospital environment. In addition, the epidemiology of A. baumannii infection is often complex, with the coexistence of epidemic and endemic infections, the latter of which often is favored by the selection pressure of antimicrobials. The only good news is that potentially severe A. baumannii infection, such as bacteremia or pneumonia in patients in the intensive care unit who are undergoing intubation, do not seem to be associated with a higher attributable mortality rate or an increased length of hospital stay.

COMMUNITY-ACQUIRED METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS INFECTIONS IN FRANCE: EMERGENCE OF A SINGLE CLONE THAT PRODUCES PANTON-VALENTINE LEUKOCIDIN

To characterize the clinical and bacteriologic characteristics of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, we reviewed 14 cases that were diagnosed in previously healthy patients during an 18-month period in France. Eleven patients had skin or soft-tissue infections. Two patients died of CA-MRSA necrotizing pneumonia. A case of pleurisy occurred in a child who acquired CA-MRSA from his mother, who had a breast abscess. The Panton-Valentine leukocidin genes and the lukE-lukD leukocidin genes were detected in all 14 isolates. The clonal origin of all of the isolates was demonstrated on the basis of their pulsotypes and antibiotic resistance profiles. All isolates had an agr3 allele. The combination of the Panton-Valentine leukocidin determinant (which encodes a virulence factor for primary skin infection and pneumonia) with the mecA gene (which confers antibiotic resistance and epidemicity) appears to have created a superadapted S. aureus strain that is spreading in the community.

Obesity-associated gut microbiota is enriched in Lactobacillus reuteri and depleted in Bifidobacterium animalis and Methanobrevibacter smithii

Background:Obesity is associated with increased health risk and has been associated with alterations in bacterial gut microbiota, with mainly a reduction in Bacteroidetes, but few data exist at the genus and species level. It has been reported that the Lactobacillus and Bifidobacterium genus representatives may have a critical role in weight regulation as an anti-obesity effect in experimental models and humans, or as a growth-promoter effect in agriculture depending on the strains.Objectives and methods:To confirm reported gut alterations and test whether Lactobacillus or Bifidobacterium species found in the human gut are associated with obesity or lean status, we analyzed the stools of 68 obese and 47 controls targeting Firmicutes, Bacteroidetes, Methanobrevibacter smithii, Lactococcus lactis, Bifidobacterium animalis and seven species of Lactobacillus by quantitative PCR (qPCR) and culture on a Lactobacillus-selective medium.Findings:In qPCR, B. animalis (odds ratio (OR)=0.63; 95% confidence interval (CI) 0.39–1.01; P=0.056) and M. smithii (OR=0.76; 95% CI 0.59–0.97; P=0.03) were associated with normal weight whereas Lactobacillus reuteri (OR=1.79; 95% CI 1.03–3.10; P=0.04) was associated with obesity.Conclusion:The gut microbiota associated with human obesity is depleted in M. smithii. Some Bifidobacterium or Lactobacillus species were associated with normal weight (B. animalis) while others (L. reuteri) were associated with obesity. Therefore, gut microbiota composition at the species level is related to body weight and obesity, which might be of relevance for further studies and the management of obesity. These results must be considered cautiously because it is the first study to date that links specific species of Lactobacillus with obesity in humans.

Comprehensive Diagnostic Strategy for Blood Culture-Negative Endocarditis: A Prospective Study of 819 New Cases

BACKGROUND. Blood culture-negative endocarditis (BCNE) may account for up to 31% of all cases of endocarditis. METHODS. We used a prospective, multimodal strategy incorporating serological, molecular, and histopathological assays to investigate specimens from 819 patients suspected of having BCNE. RESULTS. Diagnosis of endocarditis was first ruled out for 60 patients. Among 759 patients with BCNE, a causative microorganism was identified in 62.7%, and a noninfective etiology in 2.5%. Blood was the most useful specimen, providing a diagnosis for 47.7% of patients by serological analysis (mainly Q fever and Bartonella infections). Broad-range polymerase chain reaction (PCR) of blood and Bartonella-specific Western blot methods diagnosed 7 additional cases. PCR of valvular biopsies identified 109 more etiologies, mostly streptococci, Tropheryma whipplei, Bartonella species, and fungi. Primer extension enrichment reaction and autoimmunohistochemistry identified a microorganism in 5 additional patients. No virus or Chlamydia species were detected. A noninfective cause of endocarditis, particularly neoplasic or autoimmune disease, was determined by histological analysis or by searching for antinuclear antibodies in 19 (2.5%) of the patients. Our diagnostic strategy proved useful and sensitive for BCNE workup. CONCLUSIONS. We highlight the major role of zoonotic agents and the underestimated role of noninfective diseases in BCNE. We propose serological analysis for Coxiella burnetii and Bartonella species, detection of antinuclear antibodies and rheumatoid factor as first-line tests, followed by specific PCR assays for T. whipplei, Bartonella species, and fungi in blood. Broad-spectrum 16S and 18S ribosomal RNA PCR may be performed on valvular biopsies, when available.

Molecular Detection of Multiple Emerging Pathogens in Sputa from Cystic Fibrosis Patients

Background There is strong evidence that culture-based methods detect only a small proportion of bacteria present in the respiratory tracts of cystic fibrosis (CF) patients. Methodology/Principal Findings Standard microbiological culture and phenotypic identification of bacteria in sputa from CF patients have been compared to molecular methods by the use of 16S rDNA amplification, cloning and sequencing. Twenty-five sputa from CF patients were cultured that yield 33 isolates (13 species) known to be pathogens during CF. For molecular cloning, 760 clones were sequenced (7.2±3.9 species/sputum), and 53 different bacterial species were identified including 16 species of anaerobes (30%). Discrepancies between culture and molecular data were numerous and demonstrate that accurate identification remains challenging. New or emerging bacteria not or rarely reported in CF patients were detected including Dolosigranulum pigrum, Dialister pneumosintes, and Inquilinus limosus. Conclusions/Significance Our results demonstrate the complex microbial community in sputa from CF patients, especially anaerobic bacteria that are probably an underestimated cause of CF lung pathology. Metagenomic analysis is urgently needed to better understand those complex communities in CF pulmonary infections.

Long-term outcome of Q fever endocarditis: a 26-year personal survey

BACKGROUND Q fever endocarditis caused by Coxiella burnetii is a potentially fatal disease characterised by a chronic evolution. To assess the long-term outcome and identify prognostic factors for mortality, surgical treatment, and serological changes in Q fever endocarditis, we did a retrospective study in the French National Referral Centre. METHODS Patients included were diagnosed with Q fever endocarditis at our centre from May, 1983, to June, 2006, and followed up for a minimum of 3 years for each patient, history and clinical characteristics were recorded with a standardised questionnaire. Prognostic factors associated with death, surgery, serological cure, and serological relapse were assessed by Cox regression analysis. Excised heart valve analysis was assessed according to duration of treatment. FINDINGS 104 patients were identified for inclusion in the study, although one was lost to follow-up; median follow-up was 100 months (range 37-310 months). 18 months of treatment was sufficient to sterilise the valves of all the patients except three, and 2 years of treatment sterilised all valves except one. In a multivariate Cox regression analysis, the major determinants associated with mortality were age (hazard ratio 1.11, 95% CI 1.05-1.18, p=0.003), stroke at diagnosis (7.09, 2.00-25.10, p=0.001), endocarditis on a prosthetic valve (6.04, 1.47-24.80, p=0.044), an absence of a four-times decrease of phase I IgG and IgA at 1 year (5.69, 1.00-32.22, p=0.049), or the presence of phase II IgM at 1 year (12.08, 3.11-46.85, p=0.005). Surgery was associated with heart failure (2.68, 1.21-5.94, p=0.015) or a cardiac abscess (4.71, 1.64-13.50, p=0.004). The determinants of poor serological outcome were male sex (0.47, 0.26-0.86, p=0.014), a high level of phase I IgG (0.65, 0.45-0.95, p=0.027), and a delay in the start of treatment with hydroxychloroquine (0.20, 0.04-0.91, p=0.037). Factors associated with relapse were endocarditis on a prosthetic valve (21.3, 2.05-221.86, p=0.01) or treatment duration less than 18 months (9.69, 1.08-86.72, p=0.042). INTERPRETATION The optimum duration of treatment with doxycycline and hydroxychloroquine in Q fever endocarditis is 18 months for native valves and 24 months for prosthetic valves. This duration should be extended only in the absence of favourable serological outcomes. Patients should be serologically monitored for at least 5 years because of the risk of relapse. FUNDING French National Referral Centre for Q Fever.

Contribution of Systematic Serological Testing in Diagnosis of Infective Endocarditis

ABSTRACT Despite progress with diagnostic criteria, the type and timing of laboratory tests used to diagnose infective endocarditis (IE) have not been standardized. This is especially true with serological testing. Patients with suspected IE were evaluated by a standard diagnostic protocol. This protocol mandated an evaluation of the patients according to the modified Duke criteria and used a battery of laboratory investigations, including three sets of blood cultures and systematic serological testing for Coxiella burnetii, Bartonella spp., Aspergillus spp., Legionella pneumophila, and rheumatoid factor. In addition, cardiac valvular materials obtained at surgery were subjected to a comprehensive diagnostic evaluation, including PCR aimed at documenting the presence of fastidious organisms. The study included 1,998 suspected cases of IE seen over a 9-year period from April 1994 to December 2004 in Marseilles, France. They were evaluated prospectively. A total of 427 (21.4%) patients were diagnosed as having definite endocarditis. Possible endocarditis was diagnosed in 261 (13%) cases. The etiologic diagnosis was established in 397 (93%) cases by blood cultures, serological tests, and examination of the materials obtained from cardiac valves, respectively, in 348 (81.5%), 34 (8%), and 15 (3.5%) definite cases of IE. Concomitant infection with streptococci and C. burnetii was seen in two cases. The results of serological and rheumatoid factor evaluation reclassified 38 (8.9%) possible cases of IE as definite cases. Systematic serological testing improved the performance of the modified Duke criteria and was instrumental in establishing the etiologic diagnosis in 8% (34/427) cases of IE.

Dramatic Reduction in Infective Endocarditis-Related Mortality With a Management-Based Approach

BACKGROUND Despite improvements in medical and surgical therapy, infective endocarditis (IE) is still associated with a severe prognosis and remains a therapeutic challenge. We aimed to evaluate the impact of a standardized diagnostic and therapeutic protocol on mortality and to correlate the outcome with compliance with our management-based protocol. METHODS We conducted an observational before-after study that included 333 consecutive patients treated for IE at a referral center from 1991 to 2006, which was divided into 2 periods: period 1 (1991-2001), before implementation of our therapeutic protocol (n = 173), and period 2 (2002-2006), after implementation of our protocol (n = 160). Our protocol was created by a multidisciplinary task force including a sampling of biological specimens, the use of only 4 antimicrobial agents, a standardized duration of treatment, standardized surgical indications, and 1 year of close follow-up. Because our protocol was based on a local consensus by physicians and surgeons, it was not possible to randomize the study. RESULTS The 1-year mortality significantly decreased from 18.5% during period 1 to 8.2% during period 2 (hazard ratio, 0.41; 95% confidence interval, 0.21-0.79 [P = .008]). After multivariable analysis, the management during period 2 remained a strong protective factor (adjusted hazard ratio, 0.26; 95% confidence interval, 0.09-0.76 [P = .01]). During period 2, we observed a statistically significantly better compliance in antimicrobial therapy and fewer cases of renal failure. Deaths by embolic events and multiple organ failure syndrome also significantly decreased during period 2. CONCLUSION A dramatic reduction in mortality was observed during this study, suggesting that a management-based approach has a significant impact on IE outcome.