Thomas Bénet

Reduction of Invasive Aspergillosis Incidence among Immunocompromised Patients after Control of Environmental Exposure

BACKGROUND The objective of the study was to assess the impact of the relocation of an adult hematological intensive care unit on invasive aspergillosis (IA) incidence. METHODS A quasi-experimental study, including a control group and an intervention group that both underwent pretest and posttest evaluations, was conducted in the 3 adult hematological intensive care units (each composed of 14 single rooms) in a university hospital from 14 April 2005 through 1 February 2006. One of these units was relocated from the main building to an adjoining modular construction. In this unit, 4 rooms were equipped with laminar airflow before relocation; all rooms were equipped with positive pressure isolation after relocation. The 2 other units (control group), each containing 8 rooms with laminar airflow, did not undergo environmental modification. The diagnostic criteria for IA were based on the criteria of the European Organization for Research and Treatment of Cancer. RESULTS In total, 356 hospitalized patients were included. Of the 21 cases of IA, 18 were nosocomial, and 3 were of undetermined origin. In the relocated unit, the incidence of IA decreased from 13.2% (9 patients) before relocation to 1.6% (1 patient) after relocation (P=.018). Eight of the 9 patients with IA before relocation stayed in rooms without specific air treatment. The rate of IA did not change in the control group. Patient characteristics were similar in each unit before and after relocation. CONCLUSION We detected a straightforward association between environmental modification and decreased IA incidence, which emphasizes the use of an environmental strategy, including high-efficiency air filtration, in the prevention of IA.

Invasive aspergillosis in patients with hematologic malignancies: incidence and description of 127 cases enrolled in a single institution prospective survey from 2004 to 2009

Background The study objectives were: 1) to report on invasive aspergillosis patients in a hematology department; and 2) to estimate its incidence according to the hematologic diagnosis. Design and Methods A prospective survey of invasive aspergillosis cases was undertaken between January 2004 and December 2009 in the hematology department of a university hospital. Meetings with clinicians, mycologists and infection control practitioners were organized monthly to confirm suspected aspergillosis cases. Demographic characteristics, clinical and complementary examination results were recorded prospectively. Information on hospitalization was extracted from administrative databases. Invasive aspergillosis diagnosis followed the European Organization for Research and Treatment of Cancer criteria, and proven and probable IA cases were retained. A descriptive analysis was conducted with temporal trends of invasive aspergillosis incidence assessed by adjusted Poisson regression. Results Overall, 4,073 hospitalized patients (78,360 patient-days) were included in the study. In total, 127 (3.1%) patients presented invasive aspergillosis. The overall incidence was 1.6 per 1,000 patient-days (95% confidence interval: 1.4, 1.9) with a decrease of 16% per year (−1%, −28%). The incidence was 1.9 per 1,000 patient-days (1.5, 2.3) in acute myeloid leukemia patients with a decrease of 20% per year (−6%, −36%). Serum Aspergillus antigen was detected in 89 (71%) patients; 29 (23%) had positive cultures, and 118 (93%), abnormal lung CT scans. One-month mortality was 13%; 3-month mortality was 42%. Mortality tended to decrease between 2004 and 2009. Conclusions Invasive aspergillosis incidence and mortality declined between 2004 and 2009. Knowledge of invasive aspergillosis characteristics and its clinical course should help to improve the management of these patients with severe disease.

Influenza vaccination of healthcare workers in acute-care hospitals: a case-control study of its effect on hospital-acquired influenza among patients

BackgroundIn acute-care hospitals, no evidence of a protective effect of healthcare worker (HCW) vaccination on hospital-acquired influenza (HAI) in patients has been documented. Our study objective was to ascertain the effectiveness of influenza vaccination of HCW on HAI among patients.MethodsA nested case-control investigation was implemented in a prospective surveillance study of influenza-like illness (ILI) in a tertiary acute-care university hospital. Cases were patients with virologically-confirmed influenza occurring ≥ 72 h after admission, and controls were patients with ILI presenting during hospitalisation with negative influenza results after nasal swab testing. Four controls per case, matched per influenza season (2004-05, 2005-06 and 2006-07), were randomly selected. Univariate and multivariate conditional logistic regression models were fitted to assess factors associated with HAI among patients.ResultsIn total, among 55 patients analysed, 11 (20%) had laboratory-confirmed HAI. The median HCW vaccination rate in the units was 36%. The median proportion of vaccinated HCW in these units was 11.5% for cases vs. 36.1% for the controls (P = 0.11); 2 (20%) cases and 21 (48%) controls were vaccinated against influenza in the current season (P = 0.16). The proportion of ≥ 35% vaccinated HCW in short-stay units appeared to protect against HAI among patients (odds ratio = 0.07; 95% confidence interval 0.005-0.98), independently of patient age, influenza season and potential influenza source in the units.ConclusionsOur observational study indicates a shielding effect of more than 35% of vaccinated HCW on HAI among patients in acute-care units. Investigations, such as controlled clinical trials, are needed to validate the benefits of HCW vaccination on HAI incidence in patients.

The role of nucleoside and nucleotide analogues in nodular regenerative hyperplasia in HIV-infected patients: A case control study

BACKGROUND & AIMS Nodular regenerative hyperplasia (NRH) leading to non-cirrhotic portal hypertension has been described in HIV-infected patients and has been linked to didanosine. The relation between NRH and other antiretrovirals remains unclear. METHODS A case-control study was performed in 13 patients with NRH and 78 controls matched for time of inclusion, baseline CD4, and duration of follow-up. Univariate and multivariate conditional logistic regression analyses were performed. RESULTS Control patients and patients with NRH were similar at baseline regarding demographics and biological data with the exception of older age for patients with NRH (43.9 vs. 33.5 years, p=0.044). At the time of NRH diagnosis, cases had a lower CD4 count (327 vs. 468/mm(3), p=0.013), a similar CD4 percentage (24 vs. 26.2%, p=0.7), a lower platelet count (169 vs. 228 giga/L, p=0.003) and a higher AST level (33 vs. 26 IU/L, p=0.001) than controls. Univariate analysis demonstrated that patients with NRH had been exposed longer than controls to didanosine, stavudine, tenofovir, didanosine+stavudine, and didanosine+tenofovir. The age at baseline [OR 2.2 (1.0-5.0) per 10 years, p=0.053] and didanosine+stavudine cumulative exposure [OR 3.7 (1.4-10.2) per year, p=0.011] were independently associated with NRH. The age at baseline [OR 2.3 (1.0-5.3) per 10 years, p=0.045], cumulative exposure to didanosine [OR 1.4 (1.1-1.9) per year, p=0.023] and to tenofovir [OR 1.7 (1.0-2.8) per year, p=0.04] were independently associated with NRH when didanosine+stavudine exposure was excluded from the model. CONCLUSIONS NRH in HIV-infected patients seems strongly related to age and the cumulative exposure to didanosine+stavudine, didanosine, and stavudine.

Invasive aspergillosis: an important risk factor on the short- and long-term survival of acute myeloid leukemia (AML) patients

Invasive aspergillosis (IA) during induction chemotherapy of acute myeloid leukemia (AML) could worsen the prognosis. Our objective was to study how the development of IA during AML interferes with the therapeutic strategy and to evaluate its impact on the short- and long-term survival. Newly diagnosed AML patients between the years 2004 and 2007 were retrospectively analyzed. The outcome was death of the patient. A Cox proportional hazards model with the diagnosis of IA and post-induction response evaluation as the main exposure was fitted. Overall, 262 patients were analyzed and 58 IA were observed. The 2-year survival of patients having had remission of AML was 54% and, for patients with failure of chemotherapy, it was 5% (p < 0.001). The 2-year survival of patients having had IA was 14%, and without IA, it was 32% (p = 0.01). Multivariate analysis showed that IA was associated with a higher risk of death in case of remission compared to no IA (hazard ratio [HR] = 1.66 [1.05–2.65], p = 0.031) and also in case of failure (HR = 6.43, p < 0.001). IA was associated with an increased risk of death for patients if they were either in remission or in failure after induction chemotherapy.

Delta-toxin production deficiency in Staphylococcus aureus: a diagnostic marker of bone and joint infection chronicity linked with osteoblast invasion and biofilm formation

Biofilm formation, intra-osteoblastic persistence, small-colony variants (SCVs) and the dysregulation of agr, the major virulence regulon, are possibly involved in staphylococcal bone and joint infection (BJI) pathogenesis. We aimed to investigate the contributions of these mechanisms among a collection of 95 Staphylococcus aureus clinical isolates from 64 acute (67.4%) and 31 chronic (32.6%) first episodes of BJI. The included isolates were compared for internalization rate, cell damage and SCV intracellular emergence using an ex vivo model of human osteoblast infection. Biofilm formation was assessed in a microbead immobilization assay (BioFilm Ring test). Virulence gene profiles were assessed by DNA microarray. Seventeen different clonal complexes were identified among the screened collection. The staphylococcal internalization rate in osteoblasts was significantly higher for chronic than acute BJI isolates, regardless of the genetic background. Conversely, no differences regarding cytotoxicity, SCV emergence, biofilm formation and virulence gene distribution were observed. Additionally, agr dysfunction, detected by the lack of delta-toxin production using whole-cell matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) analysis (n = 15; 15.8%), was significantly associated with BJI chronicity, osteoblast invasion and biofilm formation. These findings provide new insights into MSSA BJI pathogenesis, suggesting the correlation between chronicity and staphylococcal osteoblast invasion. This adaptive mechanism, along with biofilm formation, is associated with agr dysfunction, which can be routinely assessed by delta-toxin detection using MALDI-TOF spectrum analysis, possibly providing clinicians with a diagnostic marker of BJI chronicity at the time of diagnosis.

Incidence of Hospital-Acquired Pneumonia, Bacteraemia and Urinary Tract Infections in Patients with Haematological Malignancies, 2004–2010: A Surveillance-Based Study

Objective This study charted incidence trends of hospital-acquired (HA) pneumonia, bacteraemia and urinary tract infections (UTI) in a haematology department. Methods Prospective surveillance of hospital-acquired infections (HAI) was undertaken in a 42-bed haematology department of a university hospital. All patients hospitalized ≥48 hours between 1st January 2004 and 31st December 2010 were included. Definitions of HAI were based on a standardized protocol. The incidence was the number of events per 1000 patient-days at risk; only the first HAI was counted. Multivariate Poisson regression was fitted to assess temporal trends. Results Among 3 355 patients (58 063 patient-days at risk) included, 1 055 (31%) had HAI. The incidence of HA pneumonia, HA bacteraemia and HA UTI was respectively 3.3, 12.0 and 2.9 per 1000 patient-days at risk. HA bacteraemia incidence increased by 11% (95% confidence interval: +6%, +15%, P<0.001) per year, independently of neutropenia, central venous catheterization (CVC) and haematological disease. The incidences of HA pneumonia and HA UTI were stable. The most frequently isolated pathogens were Aspergillus spp. (59.2%) for pneumonia, coagulase-negative Staphylococcus (44.2%) for bacteraemia and enterobacteria (60%) for UTI. Conclusion The incidence of bacteraemia increased, indicating that factors other than CVC exposure, including chemotherapy with its impact on the immune system, could explain this trend. Further analytic studies are needed to explore the factors that could explain this trend.

Impact of surveillance of hospital-acquired infections on the incidence of ventilator-associated pneumonia in intensive care units: a quasi-experimental study

IntroductionThe preventive impact of hospital-acquired infection (HAI) surveillance is difficult to assess. Our objective was to investigate the effect of HAI surveillance disruption on ventilator-associated pneumonia (VAP) incidence.MethodsA quasi-experimental study with an intervention group and a control group was conducted between 1 January 2004 and 31 December 2010 in two intensive care units (ICUs) of a university hospital that participated in a national HAI surveillance network. Surveillance was interrupted during the year 2007 in unit A (intervention group) and was continuous in unit B (control group). Period 1 (pre-test period) comprised patients hospitalized during 2004 to 2006, and period 2 (post-test period) involved patients hospitalized during 2008 to 2010. Patients hospitalized ≥48 hours and intubated during their stay were included. Multivariate Poisson regression was fitted to ascertain the influence of surveillance disruption.ResultsA total of 2,771 patients, accounting for 19,848 intubation-days at risk, were studied; 307 had VAP. The VAP attack rate increased in unit A from 7.8% during period 1 to 17.1% during period 2 (P <0.001); in unit B, it was 7.2% and 11.2% for the two periods respectively (P = 0.17). Adjusted VAP incidence rose in unit A after surveillance disruption (incidence rate ratio = 2.17, 95% confidence interval 1.05 to 4.47, P = 0.036), independently of VAP trend; no change was observed in unit B. All-cause mortality and length of stay increased (P = 0.028 and P = 0.038, respectively) in unit A between periods 1 and 2. In unit B, no change in mortality was observed (P = 0.22), while length of stay decreased between periods 1 and 2 (P = 0.002).ConclusionsVAP incidence, length of stay and all-cause mortality rose after HAI surveillance disruption in ICU, which suggests a specific effect of HAI surveillance on VAP prevention and reinforces the role of data feedback and counselling as a mechanism to facilitate performance improvement.

The Relevance of a Novel Quantitative Assay to Detect up to 40 Major Streptococcus pneumoniae Serotypes Directly in Clinical Nasopharyngeal and Blood Specimens.

For epidemiological and surveillance purposes, it is relevant to monitor the distribution and dynamics of Streptococcus pneumoniae serotypes. Conventional serotyping methods do not provide rapid or quantitative information on serotype loads. Quantitative serotyping may enable prediction of the invasiveness of a specific serotype compared to other serotypes carried. Here, we describe a novel, rapid multiplex real-time PCR assay for identification and quantification of the 40 most prevalent pneumococcal serotypes and the assay impacts in pneumonia specimens from emerging and developing countries. Eleven multiplex PCR to detect 40 serotypes or serogroups were optimized. Quantification was enabled by reference to standard dilutions of known bacterial load. Performance of the assay was evaluated to specifically type and quantify S. pneumoniae in nasopharyngeal and blood samples from adult and pediatric patients hospitalized with pneumonia (n = 664) from five different countries. Serogroup 6 was widely represented in nasopharyngeal specimens from all five cohorts. The most frequent serotypes in the French, South African, and Brazilian cohorts were 1 and 7A/F, 3 and 19F, and 14, respectively. When both samples were available, the serotype in blood was always present as carriage with other serotypes in the nasopharynx. Moreover, the ability of a serotype to invade the bloodstream may be linked to its nasopharyngeal load. The mean nasopharyngeal concentration of the serotypes that moved to the blood was 3 log-fold higher than the ones only found in the nasopharynx. This novel, rapid, quantitative assay may potentially predict some of the S. pneumoniae serotypes invasiveness and assessment of pneumococcal serotype distribution.

Aspergillosis: nosocomial or community-acquired?

Discrimination between nosocomial and community infections is important for investigation and prevention. Nosocomial and hospital-acquired infections require appropriate hospital control measures to avert additional cases. Nosocomial infections (NI) occur during hospitalization or are caused by microorganisms acquired during hospital stay. Such infections should not be evident when patients are admitted to the hospital. Furthermore, the definition of NI is based on epidemiological criteria, such as the time lapse between admission and onset, or microbiological criteria. This definition might be difficult to apply to invasive aspergillosis (IA) which often afflicts patients with severe immunosuppression or transplantation. Identification of the source may be difficult which could arise outside or inside the hospital. Another significant issue is the lack of valid and reproducible data on the incubation period. The incubation duration of IA is influenced by different individual or environmental determinants, including the severity of immunosuppression and air quality. The criteria of causality are also a means of discussing the contribution of hospital vs. community determinants of IA. The definition of nosocomial IA remains difficult. A better understanding of early events related to IA onset will help to prevent this disease for which the prognosis remains negative.