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Objectives Since 2003, incidences of carbapenemase-producing Gram-negative bacilli (CP-GNB) and vancomycin-resistant Enterococcus faecium (VRE) have steadily increased in France. We therefore conducted a point prevalence study to estimate carriage rates of CP-GNB, VRE and ESBL-producing Enterobacterales (ESBL-PE) and associated risk factors. Methods Between September 2019 and January 2020, all inpatients hospitalized on a given day in 11 teaching hospitals in the Paris urban area were eligible. Patient interviews and rectal swab screening results were recorded by dedicated nurses. The swabs were plated onto selective chromogenic media and processed using the GeneXpert® system. Results Of 2396 patients, 364 (15.2%) yielded at least one multiresistant bacterial isolate, including 29 CP-GNB carriers (1.2%), 13 VRE carriers (0.5%) and 338 ESBL-PE carriers (14%). In 15 patients (4.4% of ESBL-PE carriers and 36.6% of CP-GNB/VRE carriers), concomitant CP-GNB/VRE and ESBL-PE carriage was observed. In 7/29 CP-GNB and 7/13 VRE carriers, carbapenemase production and vanA in the screening samples was only detected with Xpert® tests. The OXA-48 gene was predominant in 13/34 CP-GNB isolates from 29 carriers. From the 338 ESBL-PE carriers, 372 isolates were recovered, mainly Escherichia coli (61.2%). Among 379 children, 1.1% carried a CP-GNB/VRE strain, and 12.4% carried an ESBL strain. Previous hospitalization outside mainland France, previous antimicrobial treatment and previous ESBL-PE carriage were the main risk factors associated with CP-GNB and/or VRE carriage. Conclusions The low CP-GNB and VRE prevalence likely reflects the French policy to limit intrahospital spread of CP-GNB and VRE strains.

ObjectiveHealthcare workers are at high risk of experiencing stress and fatigue due to the demands of their work within hospitals. Improving their physical and mental health and in turn, the quality and safety of care, requires considering factors at both individual and organizational levels. Using a multi-center prospective cohort, this study aims to identify the individual and organizational predictors of stress and fatigue of healthcare workers in several wards from university hospitals.MethodsOur cohort consist of 695 healthcare workers from 32 hospital wards drawn at random within four volunteer hospital centers in Paris-area. Three-level longitudinal analyses, accounting for repeated measures (level 1) across participants (level 2) nested within wards (level 3) and adjusted for relevant fixed and time varying confounders were performed.ResultsAt baseline, the sample was composed by 384 registered nurses, 300 auxiliary nurses and 11 midwives. According to the 3-level longitudinal models, some predictors were found in common for both stress and fatigue (low support from the hierarchy, low safety culture, overcommitment at work, presenteeism while sick…). However, specific predictors for high level of stress (negative life events, low support from the colleagues and high frequency of break cancellation) and fatigue (commuting duration, frequent use of interim staff in the ward…) were also found.ConclusionOur results may help identify at-risk healthcare workers and wards, where interventions to reduce stress and fatigue should be focused. These interventions could include manager training to favor better staff support and overall safety culture of healthcare workers.1.What is already known about this subject?Healthcare workers have high levels of perceived stress and fatigue, particularly in medical fields highly exposed to infectious risks.High occupational stress and fatigue can negatively affect healthcare workers behaviors in terms of absenteeism, and ultimately intention to leave as well as quality of care.Individual and organizational differences contribute to different perceptions and consequences of occupational stress and fatigue in healthcare workers.2.What are the new findings?The ward-level environment significantly influences the stress and fatigue of healthcare workers, in addition to individual factors and time variations.Hierarchy providing low support and with low safety culture, work overinvestment, presenteeism while sick, and working in smaller wards were identified as predictors of both high stress and fatigue of healthcare workers.Negative life events (whether personal or professional), low support from the colleagues and high frequency of break cancellation are specific predictors of high level of stress. While commuting duration, frequent use of interim staff and working in a medical ward were associated with high level of fatigue.3.How might this impact on policy or clinical practice in the foreseeable future?In this study, we can identify some areas for improvement to better prevent stress and fatigue for healthcare workers. High stress and fatigue can be reduced through mutual and specific organizational intervention strategies.

ObjectiveHealthcare workers (HCWs) are at high risk of experiencing stress and fatigue due to the demands of their work within hospitals. Improving their physical and mental health and, in turn, the quality and safety of care requires considering factors at both individual and organisational/ward levels. Using a multicentre prospective cohort, this study aims to identify the individual and organisational predictors of stress and fatigue of HCWs in several wards from university hospitals.MethodsOur cohort consists of 695 HCWs from 32 hospital wards drawn at random within four volunteer hospital centres in Paris-area. Three-level longitudinal analyses, accounting for repeated measures (level 1) across participants (level 2) nested within wards (level 3) and adjusted for relevant fixed and time-varying confounders, were performed.ResultsAt baseline, the sample was composed by 384 registered nurses, 300 auxiliary nurses and 11 midwives. According to the three-level longitudinal models, some predictors were found in common for both stress and fatigue (low social support from supervisors, work overcommitment, sickness presenteeism and number of beds per ward). However, specific predictors for high level of stress (negative life events, low social support from colleagues and breaks frequently cancelled due to work overload) and fatigue (longer commuting duration, frequent use of interim staff in the ward) were also found.ConclusionOur results may help identify at-risk HCWs and wards, where interventions to reduce stress and fatigue should be focused. These interventions could include manager training to favour better staff support and overall safety culture of HCWs.

In this case-control study on 564 healthcare workers of a university hospital in Paris (France), contacts without protection with coronavirus disease 2019 (COVID-19) patients or with colleagues were associated with infection with severe acute respiratory syndrome coronavirus 2, whereas working in a COVID-dedicated unit and having children kept in childcare facilities were not.

In this case-control study on 564 healthcare workers of a university hospital in Paris (France), contacts without protection with COVID-19 patients or with colleagues were associated with infection with SARS-CoV-2, while working in a COVID-dedicated unit, using public transportation and having children kept in childcare facilities were not.

BackgroundHealthcare workers (HCWs) have paid a heavy toll during the coronavirus disease 2019 (COVID-19) outbreak. Routes of transmission remain to be fully understood.MethodsThis prospective study compared a 1500-bed adult and 600-bed pediatric setting of a tertiary-care university hospital located in central Paris. From 24 February until 10 April 2020, all symptomatic HCWs were screened for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on a nasopharyngeal swab. HCWs screened positive were questioned on their profession, symptoms, and occupational and nonoccupational exposures to SARS-CoV-2.ResultsAmong 1344 HCWs tested, 373 were positive (28%) and 336 (90%) corresponding questionnaires were completed. Three hospitalizations and no deaths were reported. Most HCWs (70%) had patient-facing occupational activities (22% in COVID-19 dedicated units). The total number of HCW cases peaked on 23 March, then decreased slowly, concomitantly with a continuous increase of compliance to preventive measures (including universal medical masking and personal protective equipment [PPE] for direct care to COVID-19 patients). Attack rates were of 3.2% and 2.3% in the adult and pediatric settings, respectively (P = .0022). In the adult setting, HCWs more frequently reported exposure to COVID-19 patients without PPE (25% vs 15%, P = .046). Report of contacts with children attending out-of-home care facilities dramatically decreased over the study period.ConclusionsUniversal masking, reinforcement of hand hygiene, and PPE with medical masks for patients’ care allowed protection of HCWs and containment of the outbreak. Residual transmissions were related to persistent exposures with undiagnosed patients or colleagues and not to contacts with children attending out-of-home care facilities.

Background: From the start of the pandemic, health-care workers (HCW) have paid a heavy toll to the coronavirus desease-19 (COVID-19) outbreak. Routes of transmission however remain to be fully understood. Methods: This prospective study compared two settings of a tertiary-care university hospital located in central Paris: a 1,500-bed adult and a 600-bed paediatric setting, accounting for a total of 13,278 employees. From February 24th until April 10th, 2020, all symptomatic HCW were screened for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) on a nasopharyngeal swab. HCW screened positive were prospectively questioned by phone on their profession, symptoms, occupational and non-occupational exposures to SARS-CoV-2. Findings: Among 1344 symptomatic HCW tested, 373 were positive (28%) and 336 (90%) corresponding questionnaires were completed. Three hospitalizations and no death have been reported. Most HCW (70%) had patient-facing occupational activities and 22% in COVID-19 dedicated units. The total number of HCW cases peaked on week 13 (March 23rd, 2020) then decreased slowly until April 10th, concomitantly with a continuous increase of compliance to preventive measures (including universal medical masking for all hospital staff and personal protective equipment (PPE) for direct care to COVID-19 patients). Attack rates were of 3 · 2% and 2 · 3% in the adult and paediatric settings, respectively (p=0 · 0022). In the adult setting, HCW more frequently reported exposure to COVID-19 patients without PPE (25% versus 15%, p=0 · 046). In both settings, report of contacts with children attending out-of-home care facilities dramatically decreased all over the study period. Interpretation: In central Paris, implementation of universal masking, reinforcement of hand hygiene, social distancing and PPE with medical masks for patients’ care allowed protection of HCW and containment of the outbreak. Residual transmissions were related to persistent exposures with undiagnosed patients or colleagues and not to contacts with children attending out-of-home care facilities. Funding Statement: None. Declaration of Interests: AC reports personal fees and non-financial support from Janssen Cilag, outside the submitted work. RG reports personal fees and other from Sanofi, personal fees from MSD, personal fees from Eumedica, personal fees from Pfizer, personal fees from Frezenius, personal fees from Cubist, personal fees from Correvio, personal fees from Astellas, outside the submitted work. PF reports personal fees and nonfinancial support from MSD France, personal fees from ViiV Healthcare, non-financial support from Gilead Science, personal fees and non-financial support from Janssen Cilag, personal fees from Medtronic SAS, non-financial support from Astellas, non-financial support from GSK, outside the submitted work. MLV reports non-financial support from Biomerieux, non-financial support from Diasorin, outside the submitted work. OL reports personal fees from Pfizer, personal fees from Astellas, personal fees from MSD, personal fees from Gilead, outside the submitted work. SK reports research grants from bioMerieux, personal fees from Accelerate Diagnostics, bioMerieux, MSD and Menarini, and travel expenses from bioMerieux, Astellas, MSD and Pfizer, outside the submitted work. All other authors declare no conflict of interests. Ethics Approval Statement: This study was approved by the Ethical Review Committee for publications of the Cochin university Hospital (CLEP) (N°: AAA-2020-08012). According to French policy, a non-opposition statement was obtained for all participants, meaning that all had received written detailed information on the objectives of the study and were free to request withdrawal of their consent for participation at any time.

International audience; Background: Postoperative pneumonia (POP) is a severe complication of major lung resection. The objective of this study was to describe the current epidemiology and appropriateness of antibiotic prescriptions in severe POP, 4 years after implementation of an antimicrobial stewardship program that was based on weekly multidisciplinary review of all antibiotic therapies.Methods: This study was a retrospective analysis of a prospectively collected database. It included all cases of severe POP occurring within 30 days after major lung resection of in a 1,500-bed hospital between 2013 and 2015. Criteria for severe POP were acute respiratory failure, severe sepsis, or a rapidly extensive pulmonary infiltrate. The study collected data on incidence, clinical outcomes, and microbiological analyses. Appropriateness of antibiotic prescribing was assessed by quality indicators previously validated in the literature.Results: Over the study period, 1,555 patients underwent major lung surgery. Severe POP occurred in 91 patients (5.8%; confidence interval, 4.7%; 7.0%), with a mortality rate of 9.0% (8 of 91; confidence interval, 3.0%; 14.6%). In POP with positive microbiological results, the proportion of gram-negative bacteria other than Haemophilus was 76% (50 of 66 cases). All patients (91 of 91) had respiratory samples taken within 24 hours after the start of antibiotics; empiric therapy was concordant with the guideline in 80% (69 of 86), and it was switched to pathogen-directed therapy in 74% (46 of 62). In 71 of 91 patients (78%), the antibiotic duration was up to 7 days.Conclusions: This study reported a high proportion of gram-negative bacteria in severe POP. Four years after implementation of the program, quality indicators of antibiotic prescribing were all >70%. The rate of de-escalation to pathogen-directed therapy could be improved, however.

Stenotrophomonas maltophilia (Sm) pneumonia in immunocompromized hosts is an increasingly common nosocomial infection. Even though resistant to multiple antimicrobials, this gram-negative bacteria usually does not present with a fulminant course leading to a fatal hemorrhagic respiratory infection in neutropenic patients. We report here the case of a 63-year-old woman treated by intensive chemotherapy for acute myeloid leukemia (AML) who presented while severely neutropenic and thrombocytopenic a Sm pulmonary infection with hemoptysis leading to death in 48 h. The bronchoalveolar lavage (BAL) performed shortly before death was highly hemorrhagic and contained a striking amount of extra- and intra-cellular pathogens. Blood and BAL cultures grew S. maltophilia. Post-mortem examination revealed bilateral extensive intra-alveolar hemorrhage (IAH) associated with a great amount of microorganisms and severe bone marrow aplasia was observed without evidence of leukemia residual disease. Sm pneumonia usually does not evolve into such a devastating clinical picture although infections due to the bacteria are known to be associated with high morbidity and mortality. So far, the present observation is the fourth similar case reported in the literature. Even though an early diagnosis and an adequate antibiotic prescription may improve Sm infection prognosis, S. maltophilia proves difficult to eradicate due to a high resistance rate in part intrinsic but also in part acquired.

Objective To study the efficacy and safety of high-concentration antibiotic locks in association with systemic antibiotherapy in Staphylococcus epidermidis infections of totally implantable venous access devices (TIVADs) in patients with AIDS. Methods Thirty-one episodes of S. epidermidis TIVAD infection were observed in nine patients. Locks consisted of high concentrations of aminoglycosides or vancomycin according to antibiogram results (susceptibility results obtained with the disk diffusion technique). Genotyping of bacterial strains was performed by pulsed-field gel electrophoresis (PFGE) in 26 of the 31 infectious episodes. Results The infections occurred within a median period of 62 catheter-days. The median duration of systemic antibiotic therapy was 17.5 days in association with a median of three antibiotic locks. Failure as defined by the occurrence of a novel episode within 2 months was observed in 17 of the 31 infections (58%). According to the PFGE results, relapse with the same strain of S. epidermidis or reinfection with a different strain of S. epidermidis could be assigned to 10 episodes which failed to respond to therapy. Relapse was observed in six of 10 episodes. Four episodes were followed by the occurrence of a novel infection with a different S. epidermidis strain. In one patient, a relapse occurred despite TIVAD removal. Conclusion: Our observations further document the poor efficacy of associating antibiotic locks with systemic antibiotic therapy for the treatment of TIVAD infections in patients with AIDS.

Of 24 high-level gentamicin-resistant clinical isolates of Enterococcus faecalis , 20 carried gentamicin resistance (Gm r ) plasmids. The plasmids ranged from 65.0 to 80.0 kb in size. Three of these plasmids were nonconjugative, and 17 transferred by conjugation to an E. faecalis recipient at low frequency (10 −5 to 10 −6 transconjugants per donor). The remaining four strains had a nonconjugative chromosomal Gm r determinant. On the basis of restriction enzyme and DNA-DNA hybridization profiles, Tn 4001 -like α elements were located on the chromosome and three types of Tn 4001 -truncated structures, I, II, and III, were found to be carried by the Gm r plasmids. Structure I lacked IS 256 in the right-hand flanking extremity of Tn 4001 . Structure II was the same as structure I except that it also had a partial deletion of IS 256 in the left-hand flanking extremity of Tn 4001 . Structure III lacked both the right- and left-hand flanking extremities of Tn 4001 . One of the wild-type strains carried the Gm r determinant both on the chromosome, as a Tn 4001 -like α element, and on a conjugative plasmid, as a Tn 4001 -truncated type I structure.

The Pseudomonas aeruginosa Mus clinical isolate produces OXA-18, a pI 5.5 class D extended-spectrum β-lactamase totally inhibited by clavulanic acid (L. N. Philippon, T. Naas, A.-T. Bouthors, V. Barakett, and P. Nordmann, Antimicrob. Agents Chemother. 41:2188–2195, 1997). A second β-lactamase was cloned, and the recombinant Escherichia coli clone pPL10 expressed a pI 7.4 β-lactamase which conferred high levels of amoxicillin and ticarcillin resistance and which was partially inhibited by clavulanic acid. The 2.5-kb insert from pPL10 was sequenced, and a 266-amino-acid protein (OXA-20) was deduced; this protein has low amino acid identity with most of the class D β-lactamases except OXA-2, OXA-15, and OXA-3 (75% amino acid identity with each). OXA-20 is a restricted-spectrum oxacillinase and is unusually inhibited by clavulanic acid. OXA-20 is a peculiar β-lactamase because its translation initiates with a TTG (leucine) codon, which is rarely used as a translational origin in bacteria. Exploration of the genetic environment of oxa20 revealed the presence of the following integron features: (i) a second antibiotic resistance gene, aacA4 ; (ii) an intI1 gene; and (iii) two 59-base elements, each associated with either oxa20 or aacA4 . This integron is peculiar because it lacks the 3′ conserved region, and therefore is not a sul1 -associated integron like most of them, and because its 3′ end is located within tnpR , a gene involved in the transposition of Tn 5393 , a gram-negative transposon. P. aeruginosa Mus produces two novel and unrelated oxacillinases, OXA-18 and OXA-20, both of which are inhibited by clavulanic acid.

Background The recommended antibiotic prophylaxis by second-generation cephalosporins reduces the incidence of wound infection and empyema, but its effectiveness on postoperative pneumonias (POPs) after major lung resection lacks demonstration. We investigated risk factors and characteristics of POPs occurring when antibiotic prophylaxis by second-generation cephalosporin or an alternative prophylaxis targeting organisms responsible for bronchial colonization was used. Methods An 18-month prospective study on all patients undergoing lung resections for noninfectious disease was performed. Prophylaxis by cefamandole (3 g/24 h, over 48 hours) was used during the first 6 months, whereas amoxicillin-clavulanate (6 g/24 h, over 24 hours) was used during the subsequent 12 months. Intraoperative bronchial aspirates were systematically cultured. Patients with suspicion of pneumonia underwent bronchoscopic sampling for culture. Results Included were 168 patients in the first period and 277 patients in the second period. The incidence of POP decreased by 45% during the second period (P = 0.0027). A significant reduction in antibiotic therapy requirement for postoperative infections (P = 0.0044) was also observed. Thirty-day mortality decreased from 6.5% to 2.9% (P = 0.06). Multivariate analysis showed that type of resection, intraoperative colonization, chronic obstructive pulmonary disease, gender, body mass index, and type of prophylaxis were independent risk factors of POP. A case control-study that matched patients of the two periods according to these risk factors (except for antibiotic prophylaxis) confirmed that the incidence of POP was lowered during the second period. Conclusions Targeted antibiotic prophylaxis may decrease the rate of POPs after lung resection and improve outcome.

Postoperative pneumonia (POP) is a life-threatening complication of lung resection. The incidence, causative bacteria, predisposing factors, and outcome are poorly understood.Prospective observational study.A prospective study of all patients undergoing major lung resections for noninfectious disease was performed over a 6-mo period. Culture of intraoperative bronchial aspirates was systematically performed. All patients with suspicion of pneumonia underwent bronchoscopic sampling and culture before antibiotherapy.One hundred and sixty-eight patients were included in the study. Bronchial colonization was identified in 31 of 136 patients (22.8%) on analysis of intraoperative samples. The incidence of POP was 25% (42 of 168). Microbiologically documented and nondocumented pneumonias were recorded in 24 and 18 cases, respectively. Haemophilus species, Streptococcus species, and, to a much lesser extent, Pseudomonas and Serratia species were the most frequently identified pathogens. Among colonized and noncolonized patients, POP occurred in 15 of 31 and 20 of 105 cases, respectively (p = 0.0010; relative risk, 2.54). Death occurred in 8 of 42 patients who developed POP and in 3 of 126 of patients who did not (p = 0.0012). Patients with POP required noninvasive ventilation or reintubation more frequently than patients who did not develop POP (p0.0000001 and p = 0.00075, respectively). POP was associated with longer intensive care unit and hospital stay (p0.0000001 and p = 0.0000005, respectively). Multivariate analysis showed that chronic obstructive pulmonary disease, extent of resection, presence of intraoperative bronchial colonization, and male sex were independent risk factors for POP.Pneumonia acquired in-hospital represents a relatively frequent complication of lung resections, associated with an important percentage of postoperative morbidity and mortality.

From genomic DNA ofRalstonia pickettiiisolate PIC-1, a β-lactamase gene was cloned that encodes the oxacillinase OXA-22. It differs from known oxacillinases, being most closely related to OXA-9 (38% amino acid identity). The hydrolytic spectrum of OXA-22 is limited mostly to benzylpenicillin, cloxacillin, and restricted-spectrum cephalosporins. OXA-22-like genes were identified as single chromosomal copies in five otherR. pickettiiclinical isolates. The expression of OXA-22-like β-lactamases was inducible inR. pickettii.

A 48-y-old woman, with a previous history of neurosurgical intervention for a trigeminal neurinoma, presented with acute meningitis due to Streptococcus salivarius. There were significant changes in the petrous region, as revealed by MRI, leading to the diagnosis of associated latent subacute mastoiditis.

Over a 9-month period, 14 strains of Ralstonia pickettii were isolated from various biological samples inoculated in a blood culture medium. Molecular epidemiological investigation confirmed the relatedness of the strains. The source of the contamination proved to be the blood culture bottle caps.

In 1990, over a 6-month period, an increase from 1 to 10% in the incidence of pristinamycin resistance among coagulase-negative staphylococci was observed in four intensive care units of a Parisian hospital. Twenty-three such isolates, as well as 25 pristinamycin-susceptible Staphylococcus epidermidis isolates, were collected and typed by analyzing various bacterial constituents. Two structurally related plasmids of 7.3 and 14.3 kb, carrying the gene vga encoding resistance to pristinamycin, were detected in the 23 pristinamycin-resistant coagulase-negative staphylococci which were identified as S. epidermidis. Although related by numerous common characteristics, 20 of these 23 isolates could be divided into two types, A (17 isolates) and B (three isolates). These types were characterized on the basis of their plasmid contents and hybridization patterns obtained when the EcoRI-digested DNA was probed with plasmid pIP1551 containing an internal fragment of the insertion sequence IS256. These findings suggest that the dissemination of type A epidemic strains was, in large part, responsible for the outbreak.