A predictive score for the result of carbapenem-resistant Enterobacterales and vancomycin-resistant enterococci screening.

BACKGROUND: The duration of extensively drug-resistant bacteria (XDR) carriage depends on several factors for which the information can be difficult to recover. AIM: To determine whether past screening and clinical results of patients can predict the results of subsequent screening. METHODS: In total, 256 patients were retrospectively included from 10 healthcare centres in France from January 2014 to January 2022. We created a predictive clearance score, ranging from -5 to +7, that included the number of XDR species and the type of resistance detected in the sample, as well as the time from the last positive sample, the number of previous consecutive negative samples, and obtaining at least one negative PCR result in the collection. This score could be used for the upcoming rectal screening of a patient carrying an XDR as soon as the last screening sample was negative. FINDINGS: The negative predictive value was >99% for score ≤0. The median time to achieve XDR clearance was significantly shorter for a score of 0 (443 days (259-705)) than that based on previously published criteria. CONCLUSION: This predictive score shows high performance for the assessment of XDR clearance. Relative to previous guidelines, it could help to lift specific infection prevention and control measures earlier. Nevertheless, the decision should be made according to other factors, such as antimicrobial use and adherence to hand hygiene.

One-day prevalence of asymptomatic carriage of toxigenic and non-toxigenic Clostridioides difficile in 10 French hospitals.

BACKGROUND: Asymptomatic faecal carriage of Clostridioides difficile has been widely evaluated, but its prevalence across a wide range of clinical departments and related risk factors are not well described. The objectives of the PORTADIFF study were to evaluate the prevalence and identifying risk factors leading to asymptomatic carriage of both toxigenic and non-toxigenic C. difficile. METHODS: The PORTADIFF study was a 1-day prevalence study carried out in 10 different French hospitals. Adult patients, who agreed to participate, were included in this study and provided a fresh stool sample. C. difficile strains isolated from carriage were characterized by polymerase chain reaction (PCR) detection of tcdA, tcdB, cdtA and cdtB, and PCR ribotyping. RESULTS: In total, 721 patients were included in this study. The median age was 73 years (range 18-101 years) and the male/female ratio was 1.06. C. difficile (either toxigenic or non-toxigenic strains) was isolated from 79 (11%) patients; 42 (5.8%) strains were toxigenic. The prevalence rates of asymptomatic carriage ranged from 5% on surgical wards to 19% on long-term care wards. The main risk factors associated with asymptomatic carriage were antibiotic treatment within the preceding 3 months (81.8% vs 53.7%; P<0.01), hospitalization within the preceding 2 months (55.8% vs 33%; P<0.01), cumulative duration of hospital stay before study inclusion (mean 50.1 vs 34.5 days; P<0.047), and hospitalization on a ward with high global incidence of C. difficile infection. CONCLUSION: Eleven percent of hospitalized patients were asymptomatic carriers of toxigenic or non-toxigenic C. difficile, and may constitute a potential reservoir of C. difficile strains.

Carbapenemase-producing Enterobacterales and vancomycin-resistant Enterococcus faecium carriage in patients who have traveled in foreign countries: A single center 5-year prospective study.

BACKGROUND: Numerous patients carrying carbapenemase-producing Enterobacterales (CPE) and/or vancomycin-resistant Enterococcus faecium (VRE) in France have previously travelled abroad. The risk of spreading CPE/VRE by patients who have stayed abroad without hospitalization is underexplored. This prompted us to screen and isolate all patients who travelled abroad in the previous 12 months upon admission to our hospital. Our aim was to evaluate the efficiency of this CPE/VRE-related risk policy. METHODS: From 2014 to 2018, patients who had travelled abroad in the previous year before their admission underwent microbiological screening and were pre-emptively isolated. Contact precautions were verified and CPE/VRE cross-transmission events investigated. RESULTS: Among 1,780 screened patients, 59 (3.3%) were colonized with CPE and/or VRE, of whom 17 (29.3%) were not hospitalized abroad. Nine generated 18 readmissions. No episodes of CPE/VRE cross-transmission were related to patients with a stay abroad without hospitalization, whereas 2 patients hospitalized abroad generated one episode each, despite implementation of contact precautions reaching values from 73.6% to 87.5%. DISCUSSION: Throughout 17 admissions and 18 readmissions, patients who stayed abroad without hospitalization represented a true risk of spreading CPE/VRE, without generating cross-transmission. CONCLUSIONS: Our strategy of CPE/VRE-related risk policy is successful.

Asymptomatic carriage of extensively drug-resistant bacteria (eXDR), a simple way to assess spontaneous clearance.

The duration of eXDR carriage depends on several factors that might be difficult to recover. We aim to assess the duration of eXDR carriage by using a simple to recover parameter: the number of consecutive negative screening. 131 eXDR carriers (51 VRE and 80 CPE) were included. The number of consecutive negative screenings was strongly associated with eXDR clearance. All patients displaying at least three negative screenings over a seven-month period were never screened positive thereafter. Taking into account the number of negative screenings as a part of a case-by-case risk assessment would be helpful for the decision to maintain or lift eXDR-focused precautions.

Carriage of ESBL-producing Enterobacteriaceae in French hospitals: the PORTABLSE study.

BACKGROUND: Currently, contact precautions are recommended for patients colonized or infected with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). Recent studies have challenged this strategy. This study aimed to assess the rate of ESBL-PE faecal carriage among hospitalized patients according to type of hospital ward, and to identify risk factors associated with carriage. METHODS: A point prevalence study was conducted in five different types of hospital ward [medical, surgical, intensive care unit (ICU), after care and rehabilitation, and geriatric] in eight French hospitals. All patients included in the study provided a fresh stool sample. RESULTS: In total, 554 patients were included in the study, with a median age of 73 years (range 60-82 years). The overall faecal carriage rate of ESBL-PE was 17.7%. The most frequently encountered species among ESBL-PE was Escherichia coli (71.4%), followed by Klebsiella pneumoniae (14.3%). Risk factors associated with ESBL-PE faecal carriage on univariate analysis were: living in the Paris region (P<0.01) and hospitalization on a geriatric ward (P<0.01). Interestingly, the cumulative duration of hospital stay before screening was not associated with a significantly higher prevalence of ESBL-PE carriage, regardless of ward type. The ESBL-PE colonization rate was much higher for patients hospitalized on geriatric wards (28.1%) and ICUs (21.7%) compared with those for patients hospitalized on surgical wards (14.8%), medical wards (12.8%) or aftercare and rehabilitation (11.2%). CONCLUSION: The overall prevalence of ESBL-PE faecal carriage was 17.7%, with only 21% of patients identified previously as carriers. The delay between admission and screening was not associated with an increase in ESBL-PE faecal carriage.

[Management of the Legionella-link risk in a multicentre area's hospital: lessons learned of a six-year experience]. / Gestion des risques liés aux légionelles dans un centre hospitalier multisites : retour d'expérience de plus de six années.

To reduce the Legionella-linked risk in the several sites of Sud-Francilien Hospital, following a hospital-acquired legionellosis case, a multidisciplinary working group performed an action plan monitored through Legionella pneumophila counts in hot water supply. From 2003 to the first half year 2009, positive points for Legionella pneumophila in the main sites of the hospital decreased from 85.71 to 28.00%, representing a significant reduction of 67.33%. Similar results were observed for three of the four establishments, whereas the last did not describe a pronounced reduction of Legionella pneumophila counts and showed constantly serogroup 1 strains. During this period, investigations of additional cases of legionellosis demonstrated a nosocomial transmission in one case in this last site. Multidisciplinary mobilization in management of Legionella-linked risk contributed to these results.

[Macrophage activation syndrome in primary human herpes virus-6 infection: a rare condition after liver transplantation in infants]. / Syndrome d'activation macrophagique au cours de la primo-infection pat le 6e virus herpétique humain: une affection certainement méconnue au cours de la transplantation hépatique chez l'enfant.

Human herpes virus-6 primary infection generally occurs during the first three years of childhood and is generally asymptomatic. The virus has been identified as the causal agent of exanthemum subitum in children or mononucleosis-like disease in adults, and may also cause several disorders in immunocompromised patients. We report a clinical case of acute rejection observed 29 days after orthotopic liver transplantation in a 22-month-old child associated with acute hepatitis and a hemophagocytic syndrome on day 38. Human herpes virus-6 primary infection was identified based on several virological tests: seroconversion, detection of viral DNA in bone marrow and peripheral blood after polymerase chain reaction, and detection of viral replication in peripheral blood. Tests for Epstein-Barr virus, cytomegalovirus or Parvovirus B19 infections were negative. After treatment by ganciclovir (Cymévan(R)), clinical status improved.

Differences in kinetics of human cytomegalovirus cell-free viral release after in vitro infection of human microglial cells, astrocytes and monocyte-derived macrophages.

Microglial cells and astrocytes isolated from human embryonic proencephalon were compared to monocyte-derived macrophages (MDM) for their ability to replicate human cytomegalovirus (HCMV) in vitro. A specific cytopathic effect was observed in microglial cells and astrocytes, but not in MDM. A high percentage of glial cells but a low percentage of MDM expressed immediate-early and late viral antigens. The ability of HCMV-infected microglial cells and astrocytes to release viral particles in their supernatants was significantly higher than that of infected MDM. Human microglial cells and astrocytes at an early stage of development are highly susceptible to HCMV infection.

Human parvovirus B19 infection in organ transplant recipients.

We report a 61-yr-old kidney transplant recipient with human Parvovirus B19 (HPV B19) infection presenting as a severe pancytopenia 1 month after transplantation. Bone marrow aspiration revealed severe erythroid hypoplasia with giant and dystrophic proerythroblasts. Bone marrow cells were positive for HPV B19 DNA detected by polymerase chain reaction (PCR). Pancytopenia resolved shortly after administration of intravenous immunoglobulins. Nineteen cases of HPV B19 infection in organ transplant recipients have been so far reported in the literature. Immunocompromised patients should be considered at risk from developing symptomatic HPV B19 infections. In such patients, specific anti-HPV B19 IgM and IgG antibodies may be absent or transient and therefore their negativity cannot rule out the diagnosis of HPV B19 infestation. Bone marrow smear morphological findings may suggest the diagnosis but testing for viral DNA by PCR is mandatory. Patients may spontaneously recover. However, since specific anti-viral therapy is not currently available, intravenous immunoglobulin administration appears to be the more efficacious treatment.

Cytomegalovirus retinitis in advanced HIV-infected patients treated with protease inhibitors: incidence and outcome over 2 years.

We prospectively studied the incidence of cytomegalovirus (CMV) retinitis in 93 patients treated with highly active antiretroviral therapy (HAART) containing a protease inhibitor (PI), during a median follow-up period of 24 months. The median initial CD4+ count was 22 cells/microl (range, 1-311 cells/microl), and the median plasma HIV viral load was 5.1 log10 copies/ml (range, 2.4-6.4 log10 copies/ml). The fundus was examined monthly in patients with a history of CMV retinitis or an initial CD4+ count <50 cells/microl and every 3 months in the other patients. Of patients with previously controlled CMV retinitis, 1 of 7 relapsed. In addition, 6 of 59 patients with a CD4+ count <50 cells/microl and no history of CMV retinitis before starting PI therapy developed CMV retinitis. Of them, 3 had at least one relapse during follow-up. CD4+ counts were <40 cells/microl at the time of primary or recurrent CMV retinitis, except in two cases (147 cells/microl and 203 cells/microl). In conclusion, the incidence of CMV retinitis was 0.091 per patient-year among study subjects with advanced HIV infection who were receiving HAART (95% confidence interval [CI], 0.037-0.145). The time to progression of CMV retinitis (mean, 215 days; 95% CI, 113-317 days) was longer than reported before widespread use of PIs.

[Incidence and evaluation of viral retinitis in patients infected with the HIV virus and treated with HIV protease inhibitors]. / Etude de l'incidence et de l'évolution des rétinites virales chez les patients infectés par le VIH et traités par les inhibiteurs de protéase du VIH.

BACKGROUND: Since the beginning of the use of HIV-Protease Inhibitors (PI) to treat HIV-infected patients, a decrease of the incidence of extraocular opportunistic infections has been observed. We studied the incidence of CMV-retinitis in patients treated with a highly active antitetroviral therapy (HAART) containing PI over a mean follow-up of 12 months. METHODS: Ninety-three HIV-infected patients treated with HAART containing PI were included. The mean initial CD4+ cell-count was 54/microliter (median: 22/microliter), and the mean plasma HIV-load was 5.46 log 10 RNA-copies/ml. Fundus examination was performed each month in case of a previously treated and controlled CMV-retinitis or if initial CD4 cells were below 50/microliter. In other patients, fundus examination was performed every 3 months. The mean follow-up was 362 days. RESULTS: Among the 7 patients with a previously treated and controlled CMV-retinitis, one experienced a progression during the study (after 163 days of PI). Among the 59 patients with CD4 cells below 50/microliter and without previous CMV-retinitis before the beginning of PI, 5 experienced a CMV-retinitis (mean delay after the onset of HAART: 141 days), including 2 with relapse. When retinitis occurred, CD4 cells were below 32/microliter except in one case (147/microliter). CONCLUSIONS: Compared to previously published reports, this study showed an increase of the time to progression of previously treated and controlled CMV-retinitis in patients treated with PI. Considering deeply immunocompromised patients (less than 50 CD4-cells/microliter), the risk of suffering from CMV-retinitis was 8.5% after 12 months of PI treatment. Longer follow-up remains necessary to confirm these results.

[Productive replication of human cytomegalovirus in primary microglial cells]. / Réplication productive du cytomégalovirus humain dans des cultures primaires de cellules microgliales.

Human cytomegalovirus (HCMV) infection can result in neurological symptoms. In vitro replication of the HCMV was studied in primary cultures of microglial cells from the central nervous systems (CNS) of human embryos. The microglial cells were infected with various amounts of either the AD169 laboratory HCMV strain or a clinical HCMV isolate. A specific cytopathic effect occurred within 24 h and persisted for two months. Immunocytochemical tests for immediate early and late viral antigens done one and three days after the infection demonstrated that 60% to 80% of the microglial cells were infected and that 3% to 8% were the site of viral DNA replication. Kinetic studies showed accumulation of viral particles in the supernatant during the first two weeks after the infection. Prestimulation of the cells by PMA 24 h before the infection was associated with increased release of viral particles and with an increased percentage of cells expressing late viral antigens. The microglial cells of the human embryonic CNS are fully permissive targets for the HCMV. The in vitro HCMV model used in this study may prove useful for investigating the pathophysiology of HCMV encephalitis, in particular after mother-to-fetus transmission of the virus.

Differential nitric oxide (NO) production by macrophages from mice and guinea pigs infected with virulent and avirulent Legionella pneumophila serogroup 1.

L-arginine-dependent reactive nitrogen intermediates have been identified as macrophage cytotoxic effector molecules against intracellular pathogens. To determine its role, ex vivo production of NO by peritoneal macrophages of C3H/HeN mice and Dunkin-Hartley guinea pigs infected intraperitoneally with a virulent and isogenic avirulent Legionella pneumophila serogroup 1 strain was compared with bacterial clearance from the lungs. While the virulent strain was cleared from mice lungs, the guinea pigs died within 96 h. In vivo infection with both strains resulted in the production of NO by mouse peritoneal macrophages ex vivo. In contrast, guinea pig macrophages did not produce detectable NO. In addition, infection by the avirulent strain led to the production of significantly more NO by mouse macrophages than the virulent parent strain, irrespective of stimulation with lipopolysaccharide (LP) and/or interferon-gamma (ifn-gamma). These results suggest that resistance to Leg. pneumophila infection may depend on the production of NO by host macrophages.