Incidence of Asymptomatic and Symptomatic Influenza Among Healthcare Workers: A Multicenter Prospective Cohort Study.

BACKGROUND: Influenza is an important cause of viral hospital-acquired infection involving patients, healthcare workers (HCW), and visitors. The frequency of asymptomatic influenza among HCW with possible subsequent transmission is poorly described. The objective is to determine the cumulative incidence of asymptomatic, paucisymptomatic, and symptomatic influenza among HCW. METHOD: A multicenter prospective cohort study was done in 5 French university hospitals, including 289 HCW during the 2016-2017 influenza season. HCW had 3 physical examinations (time [T] 0, before epidemic onset; T.1, before epidemic peak; T.2, T.3, after epidemic peak). A blood sample was taken each time for influenza serology and a nasal swab was collected at T1 and T2 for influenza detection by polymerase chain reaction (PCR). Positive influenza was defined as either a positive influenza PCR, and/or virus-specific seroconversion against influenza A, the only circulating virus, with no vaccination record during follow-up. Symptoms were self-reported daily between T1 and T2. Cumulative incidence of influenza was stratified by clinical presentation per 100 HCW. RESULTS: Of the 289 HCW included, 278 (96%) completed the entire follow-up. Overall, 62 HCW had evidence of influenza of whom 46.8% were asymptomatic, 41.9% were paucisymptomatic, and 11.3% were symptomatic. Cumulative influenza incidence was 22.3% (95% confidence interval [CI]: 17.4%-27.2%). Cumulative incidence of asymptomatic influenza was 5.8% (95% CI: 3.3%-9.2%), 13.7% (95% CI: 9.9%-18.2%) for paucisymptomatic influenza, and 2.9% (95% CI: 1.3%-5.5%) for symptomatic influenza. CONCLUSIONS: Asymptomatic and paucisymptomatic influenza were frequent among HCW, representing 47% and 42% of the influenza burden, respectively. These findings highlight the importance of systematic implementation of infection control measures among HCW regardless of respiratory symptoms from preventing nosocomial transmission of influenza. CLINICAL TRIALS REGISTRATION: NCT02868658.

Enterobacter cloacae colonisation and infection in a neonatal intensive care unit: retrospective investigation of preventive measures implemented after a multiclonal outbreak.

BACKGROUND: Enterobacter cloacae species is responsible for nosocomial outbreaks in vulnerable patients in neonatal intensive care units (NICU). The environment can constitute the reservoir and source of infection in NICUs. Herein we report the impact of preventive measures implemented after an Enterobacter cloacae outbreak inside a NICU. METHODS: This retrospective study was conducted in one level 3 NICU in Lyon, France, over a 6 year-period (2012-2018). After an outbreak of Enterobacter cloacae infections in hospitalized neonates in 2013, several measures were implemented including intensive biocleaning and education of medical staff. Clinical and microbiological characteristics of infected patients and evolution of colonization/infection with Enterobacter spp. in this NICU were retrieved. Moreover, whole genome sequencing was performed on 6 outbreak strains. RESULTS: Enterobacter spp. was isolated in 469 patients and 30 patients developed an infection including 2 meningitis and 12 fatal cases. Preventive measures and education of medical staff were not associated with a significant decrease in patient colonisation but led to a persistent decreased use of cephalosporin in the NICU. Infection strains were genetically diverse, supporting the hypothesis of multiple hygiene defects rather than the diffusion of a single clone. CONCLUSIONS: Grouped cases of infections inside one setting are not necessarily related to a single-clone outbreak and could reveal other environmental and organisational problematics. The fight against implementation and transmission of Enterobacter spp. in NICUs remains a major challenge.

Unexpected categories at risk of S. aureus nasal carriage among hospital workers.

OBJECTIVES: Thirty percent of the general population are Staphylococcus aureus nasal carriers. It has been shown that this increases with repeated contact with patients, but it is not known whether all categories of healthcare workers are at equal risk of carriage. We aimed to explore S. aureus nasal carriage among healthcare professionals. METHODS: Prospective study conducted in two French university hospitals in 2014 and 2016. Volunteers were screened for S. aureus nasal carriage. Profession and hygiene habits were collected. Based on the results of this initial study, a second study focused on semi-skilled workers and biomedical equipment technicians (BETs) only; participants were given education on the basic rules of hygiene, then re-screened three months later. RESULTS: In the initial study, 38.8% of the 436 participants were detected as nasal carriers. There was a significant difference in nasal carriage according to professional category (p < 0.0001); the lowest was found among administrative agents (17.3%), followed by healthcare providers (37.4%), laboratory technicians (37.6%). The greatest proportion was found among semi-skilled workers and BETs (52.9%). Spa-typing ruled out the hypothesis of a single clone dissemination among colleagues. After the three-month hygiene awareness campaign, all re-screened individuals remained positive, and with their respective initial strain. CONCLUSIONS: To the best of our knowledge we report here for the first time that semi-skilled workers and BETs are specifically more at risk of S. aureus nasal colonisation. This striking finding urges hospital hygiene departments to evaluate this specific professional category and implement strategies to improve hygiene awareness.

Relevance of Modified Debridement-Irrigation, Antibiotic Therapy and Implant Retention Protocol for the Management of Surgical Site Infections: A Series of 1694 Instrumented Spinal Surgery.

Introduction: Management of surgical site infections (SSI) after instrumented spinal surgery remains controversial. The debridement-irrigation, antibiotic therapy and implant retention protocol (DAIR protocol) is safe and effective to treat deep SSI occurring within the 3 months after instrumented spinal surgery. Methods: This retrospective study describes the outcomes of patients treated over a period of 42 months for deep SSI after instrumented spinal surgery according to a modified DAIR protocol. Results: Among 1694 instrumented surgical procedures, deep SSI occurred in 46 patients (2.7%): 41 patients (89%) experienced early SSI (< 1 month), 3 (7%) delayed SSI (from 1 to 3 months), and 2 (4%) late SSI (> 3months). A total of 37 patients had a minimum 1 year of follow-up; among these the modified DAIR protocol was effective in 28 patients (76%) and failed (need for new surgery for persistent signs of SSI beyond 7 days) in 9 patients (24%). Early second-look surgery (≤ 7days) for iterative debridement was performed in 3 patients, who were included in the cured group. Among the 9 patients in whom the modified DAIR protocol failed, none had early second-look surgery; 3 (33%) recovered and were cured at 1 year follow-up, and 6 (66%) relapsed. Overall, among patients with SSI and a minimum 1 year follow-up, the modified DAIR protocol led to healing in 31/37 (84%) patients. Conclusions: The present study supports the effectiveness of a modified DAIR protocol in deep SSI occurring within the 3 months after instrumented spinal surgery. An early second-look surgery for iterative debridement could increase the success rate of this treatment.

Nontuberculous Mycobacteria: An Underestimated Cause of Bioprosthetic Valve Infective Endocarditis.

Background. Atypical mycobacteria, or nontuberculous mycobacteria (NTM), have been barely reported as infective endocarditis (IE) agents. Methods. From January 2010 to December 2013, cardiac valve samples sent to our laboratory as cases of blood culture-negative suspected IE were analyzed by 16S rDNA polymerase chain reaction (PCR). When positive for NTM, hsp PCR allowed species identification. Demographic, clinical, echocardiographic, histopathological, and Ziehl-Neelsen staining data were then collected. Results. Over the study period, 6 of 370 cardiac valves (belonging to 5 patients in 3 hospitals) were positive for Mycobacterium chelonae (n = 5) and Mycobacterium lentiflavum (n = 1) exclusively on bioprosthetic material. The 5 patients presented to the hospital for heart failure without fever 7.1-18.9 months (median 13.1 months) after biological prosthetic valve implantation. Echocardiography revealed paravalvular regurgitation due to prosthesis dehiscence in all patients. Histopathological examination of the explanted material revealed inflammatory infiltrates in all specimens, 3 of which were associated with giant cells. Gram staining and conventional cultures remained negative, whereas Ziehl-Neelsen staining showed acid-fast bacilli in all patients. Allergic etiology was ruled out by antiporcine immunoglobulin E dosages. These 5 cases occurred exclusively on porcine bioprosthetic material, revealing a statistically significant association between bioprosthetic valves and NTM IE (P < .001). Conclusions. The body of evidence confirmed the diagnosis of prosthetic IE. The statistically significant association between bioprosthetic valves and NTM IE encourages systematic Ziehl-Neelsen staining of explanted bioprosthetic valves in case of early bioprosthesis dysfunction, even without an obvious sign of IE. In addition, we strongly question the cardiac bioprosthesis conditioning process after animal sacrifice.

Evaluation of syndromic algorithms for detecting patients with potentially transmissible infectious diseases based on computerised emergency-department data.

BACKGROUND: The objective of this study was to ascertain the performance of syndromic algorithms for the early detection of patients in healthcare facilities who have potentially transmissible infectious diseases, using computerised emergency department (ED) data. METHODS: A retrospective cohort in an 810-bed University of Lyon hospital in France was analysed. Adults who were admitted to the ED and hospitalised between June 1, 2007, and March 31, 2010 were included (N=10895). Different algorithms were built to detect patients with infectious respiratory, cutaneous or gastrointestinal syndromes. The performance parameters of these algorithms were assessed with regard to the capacity of our infection-control team to investigate the detected cases. RESULTS: For respiratory syndromes, the sensitivity of the detection algorithms was 82.70%, and the specificity was 82.37%. For cutaneous syndromes, the sensitivity of the detection algorithms was 78.08%, and the specificity was 95.93%. For gastrointestinal syndromes, the sensitivity of the detection algorithms was 79.41%, and the specificity was 81.97%. CONCLUSIONS: This assessment permitted us to detect patients with potentially transmissible infectious diseases, while striking a reasonable balance between true positives and false positives, for both respiratory and cutaneous syndromes. The algorithms for gastrointestinal syndromes were not specific enough for routine use, because they generated a large number of false positives relative to the number of infected patients. Detection of patients with potentially transmissible infectious diseases will enable us to take precautions to prevent transmission as soon as these patients come in contact with healthcare facilities.

Methicillin-resistant Staphylococcus capitis with reduced vancomycin susceptibility causes late-onset sepsis in intensive care neonates.

BACKGROUND: Coagulase-negative staphylococci, mainly Staphylococcus epidermidis, are the most frequent cause of late-onset sepsis (LOS) in the neonatal intensive care unit (NICU) setting. However, recent reports indicate that methicillin-resistant, vancomycin-heteroresistant Staphylococcus capitis could emerge as a significant pathogen in the NICU. We investigated the prevalence, clonality and vancomycin susceptibility of S. capitis isolated from the blood of NICU infants and compared these data to adult patients. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a retrospective laboratory-based survey of positive blood cultures in NICU infants ≥ 3 days of age (n = 527) and in adult ICU patients ≥ 18 years of age (n = 1473) who were hospitalized from 2004 to 2009 in two hospital centers in Lyon, France. S. capitis was the most frequent pathogen in NICU infants, ahead of S. epidermidis (39.1% vs. 23.5% of positive blood cultures, respectively). Conversely, S. capitis was rarely found in adult ICU patients (1.0%) compared to S. epidermidis (15.3%). S. capitis bloodstream isolates were more frequently resistant to methicillin when collected from NICU infants than from adult patients (95.6% vs. 53.3%, respectively). Furthermore, we collected and characterized 53 S. capitis bloodstream isolates from NICU infants and adult patients from six distant cities. All methicillin-resistant S. capitis isolates from NICU infants were clonally related as determined by pulsed-field gel electrophoresis. These isolates harbored a type V-related staphylococcal chromosomal cassette mec element, and constantly showed either vancomycin resistance (37.5%) or heteroresistance (62.5%). Conversely, the isolates that were collected outside of the NICU were genetically diverse and displayed much lower rates of vancomycin resistance and heteroresistance (7.7% and 23.1%, respectively). CONCLUSIONS/SIGNIFICANCE: A clonal population of methicillin-resistant S. capitis strains has spread into several French NICUs. These isolates exhibit reduced susceptibility to vancomycin, which is the most widely used antimicrobial agent in the NICU setting.

Early-onset ventilator-associated pneumonia incidence in intensive care units: a surveillance-based study.

BACKGROUND: The incidence of ventilator-associated pneumonia (VAP) within the first 48 hours of intensive care unit (ICU) stay has been poorly investigated. The objective was to estimate early-onset VAP occurrence in ICUs within 48 hours after admission. METHODS: We analyzed data from prospective surveillance between 01/01/2001 and 31/12/2009 in 11 ICUs of Lyon hospitals (France). The inclusion criteria were: first ICU admission, not hospitalized before admission, invasive mechanical ventilation during first ICU day, free of antibiotics at admission, and ICU stay ≥ 48 hours. VAP was defined according to a national protocol. Its incidence was the number of events per 1,000 invasive mechanical ventilation-days. The Poisson regression model was fitted from day 2 (D2) to D8 to incident VAP to estimate the expected VAP incidence from D0 to D1 of ICU stay. RESULTS: Totally, 367 (10.8%) of 3,387 patients in 45,760 patient-days developed VAP within the first 9 days. The predicted cumulative VAP incidence at D0 and D1 was 5.3 (2.6-9.8) and 8.3 (6.1-11.1), respectively. The predicted cumulative VAP incidence was 23.0 (20.8-25.3) at D8. The proportion of missed VAP within 48 hours from admission was 11% (9%-17%). CONCLUSIONS: Our study indicates underestimation of early-onset VAP incidence in ICUs, if only VAP occurring ≥ 48 hours are considered to be hospital-acquired. Clinicians should be encouraged to develop a strategy for early detection after ICU admission.

Estimating attributable mortality due to nosocomial infections acquired in intensive care units.

BACKGROUND: The strength of the association between intensive care unit (ICU)-acquired nosocomial infections (NIs) and mortality might differ according to the methodological approach taken. OBJECTIVE: To assess the association between ICU-acquired NIs and mortality using the concept of population-attributable fraction (PAF) for patient deaths caused by ICU-acquired NIs in a large cohort of critically ill patients. SETTING: Eleven ICUs of a French university hospital. DESIGN: We analyzed surveillance data on ICU-acquired NIs collected prospectively during the period from 1995 through 2003. The primary outcome was mortality from ICU-acquired NI stratified by site of infection. A matched-pair, case-control study was performed. Each patient who died before ICU discharge was defined as a case patient, and each patient who survived to ICU discharge was defined as a control patient. The PAF was calculated after adjustment for confounders by use of conditional logistic regression analysis. RESULTS: Among 8,068 ICU patients, a total of 1,725 deceased patients were successfully matched with 1,725 control patients. The adjusted PAF due to ICU-acquired NI for patients who died before ICU discharge was 14.6% (95% confidence interval [CI], 14.4%-14.8%). Stratified by the type of infection, the PAF was 6.1% (95% CI, 5.7%-6.5%) for pulmonary infection, 3.2% (95% CI, 2.8%-3.5%) for central venous catheter infection, 1.7% (95% CI, 0.9%-2.5%) for bloodstream infection, and 0.0% (95% CI, -0.4% to 0.4%) for urinary tract infection. CONCLUSIONS: ICU-acquired NI had an important effect on mortality. However, the statistical association between ICU-acquired NI and mortality tended to be less pronounced in findings based on the PAF than in study findings based on estimates of relative risk. Therefore, the choice of methods does matter when the burden of NI needs to be assessed.

Early- and late-onset ventilator-associated pneumonia acquired in the intensive care unit: comparison of risk factors.

PURPOSE: To compare risk factors of early- (E) and late-onset (L) ventilator-associated pneumonia (VAP). MATERIALS AND METHODS: An epidemiological survey based on a nosocomial infection surveillance program of 11 intensive care units (ICUs) of university teaching hospitals in Lyon, France, was conducted. A total of 7236 consecutive ventilated patients, older than 18 years and hospitalized in ICUs for at least 48 hours, were studied between 1996 and 2002. Data during ICU stay, patient-dependent risk factors, device exposure, nosocomial infections occurrence, and outcome were collected. The cutoff point definition between E-VAP (six days) was based on the daily hazard rate of VAP. RESULTS: The VAP incidence rate was 13.1%, 356 (37.6%) E-VAP (within 6 days of admission) and 590 (62.4%) L-VAP were reported. Independent risk factor for E-VAP vs L-VAP was surgical diagnostic category (odds ratio [OR], 1.49 [95% confidence interval, 1.07-2.07]), whereas independent risk factors for L-VAP vs E-VAP were older age (OR, 1.01 [1.01-1.02]), high Simplified Acute Physiology Score II (OR, 1.01 [1.00-1.02]), infection on admission (OR=2.22 [1.61-3.03]), another nosocomial infection before VAP (OR, 5.88 [3.33-11.11]), and exposure to central venous catheter before VAP (OR, 4.76 [1.04-20.00]). CONCLUSIONS: E-VAP and L-VAP have different risk factors, highlighting the need for developing specific preventive measures.

Aseptic meningitis after neurosurgery: a demonstration of bacterial involvement.

OBJECTIVE: To evaluate the presence of bacteria in samples from patients suffering from 'aseptic' meningitis following craniotomy. METHODS: Prospective study in which cerebrospinal fluid (CSF) from patients suffering from post-craniotomy meningitis and negative control patients were submitted to conventional culture and to polymerase chain reaction (PCR) using bacterial 16S rRNA universal primers, followed in some cases by DNA sequencing of the PCR product and phylogenetic analysis. RESULTS: CSF from patients with either culture-positive or culture-negative meningitis yielded positive amplifications, whereas no amplification was obtained with CSF from control patients. All positive signals were confirmed by Southern hybridization with a prokaryote 16S RNA-specific probe. Six PCR products, of which three were collected from later cases of culture-negative meningitis, were cloned and sequenced. Sequence analysis suggested affinities with Pseudomonas in three cases, with Escherichia in two cases and with Rhodococcus in one case. CONCLUSIONS: Many cases of culture-negative (aseptic) meningitis are probably bacterial meningitis and justify antibiotic treatment. The bacteria responsible for these cases of culture-negative meningitis might have peculiar growth requirements in vitro.