Brigitte Dunais

Prevalence of day-care centre children (France) with faecal CTX-M-producing Escherichia coli comprising O25b:H4 and O16:H5 ST131 strains

OBJECTIVES Determining the prevalence of children in day-care centres (DCCs) carrying faecal extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and molecularly characterizing those belonging to the Escherichia coli species. METHODS Stools were collected from childrens diapers (January-April 2012) in randomly chosen DCCs and plated onto ChromID ESBL. Colonies growing on this medium were identified by the Vitek 2 system and tested for antibiotic susceptibility and for ESBL production by the double-disc synergy test. ESBL genotypes were determined as well as phylogenetic groups, ERIC-2 (enterobacterial repetitive intergenic consensus) PCR profiles and sequence types (STs) for the E. coli isolates. Serotypes, virotypes, fimH alleles, ESBL-carrying plasmids and PFGE patterns were determined for the ST131 E. coli isolates. RESULTS Among 419 children from 25 participating DCCs, 1 was colonized by CTX-M-15-producing Klebsiella pneumoniae and 27 (6.4%) by E. coli, which all produced CTX-M enzymes [CTX-M-15 (37%), CTX-M-1 (26%), CTX-M-14 (22%), CTX-M-27 (11%) and CTX-M-22 (4%)]. The 27 E. coli isolates, 55.5% belonging to group B2, displayed 20 ERIC-2 PCR profiles and 16 STs. The ST131 E. coli isolates were dominant (44%), displayed serotypes O25b:H4 and O16:H5, fimH alleles 30 and 41 and virotypes A and C. According to the PFGE patterns, one strain of E. coli ST131 producing a CTX-M-15 enzyme carried by an IncF F2:A1:B- plasmid had spread within one DCC. CONCLUSIONS This study shows a notable prevalence (6.4%) of DCC children with faecal CTX-M-producing E. coli isolates comprising a high proportion of E. coli ST131 isolates, suggesting that these children might be a reservoir of this clone.

Can high central nervous system penetrating antiretroviral regimens protect against the onset of HIV-associated neurocognitive disorders?

Objective:To assess changes over time in neuropsychological test results (NPr) and risk factors among a regularly followed HIV-infected patient population. Methods:Prospective cohort of HIV-infected patients randomly selected to undergo neuropsychological follow-up. Test score was adjusted for age, sex and education. Patients were divided into five groups: normal tests, neuropsychological deficit (one impaired cognitive domain), asymptomatic neurocognitive disorders (ANIs), mild neurocognitive disorders (MNDs) and HIV-associated dementia (HAD). Demographic and background parameters including CSF drug concentration penetration effectiveness (CPE) score 2010 were recorded. Changes in NPr and associated risk factors were analyzed. Results:Two hundred and fifty-six patients underwent neuropsychological tests and 96 accepted follow-up approximately 2 years later. The groups were comparable. Upon neuropsychological retesting, six patients improved, 31 worsened and 59 were stable. The proportion of patients with HIV-associated neurocognitive disorders (HANDs) rose from 26 to 45%, with ANIs and MNDs still mostly represented. Most patients initially diagnosed with HANDs remained stable, five of 25 showed clinical improvement and three of 25 deteriorated. Of 33 patients with normal tests, four deteriorated, whereas 24 of 38 with initial neuropsychological deficit had poorer NPr, and contributed most of the new HAND cases. Patients with clinical deterioration had a lower CPE score both at inclusion (6.9 vs. 8.1; P = 0.005) and at the end of follow-up (7.2 vs. 7.8; P = 0.08) than those with improved or stable performance. This was confirmed by multivariate analysis. Conclusion:Patients with higher CPE scores upon inclusion and at the end of follow-up were at lower risk of clinical worsening, suggesting that combination antiretroviral therapy with better CSF penetration could protect against cognitive deterioration.

TRENDS IN NASOPHARYNGEAL CARRIAGE OF STREPTOCOCCUS PNEUMONIAE AMONG CHILDREN ATTENDING DAYCARE CENTERS IN SOUTHEASTERN FRANCE FROM 1999 TO 2006

Pneumococcal nasopharyngeal carriage, serotype distribution, and penicillin-susceptibility were monitored among children attending daycare centers in France from 1999 to 2006 to assess the impact of pneumococcal conjugate vaccine and antibiotic-reducing policies. Pneumococcal carriage remained stable. Immunization rates reached 68% in 2006. Serotype distribution shifted significantly from vaccine serotypes to vaccine-related and nonvaccine serotypes. Antibiotic treatments fell by 50%.

Influence of child care on nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae.

Background. Children cared for by a child minder (CM) should be less exposed to upper respiratory tract infections than those in group day care (GDC) and therefore to antibiotic treatment. Thus fewer CM children should carry resistant bacteria. To test this hypothesis nasopharyngeal carriage of Streptococcus pneumoniae (SP) and Haemophilus influenzae (HI) and exposure to recent antibiotic treatment were investigated among children in both types of care settings in the Alpes Maritimes (France) between November 1999 and March 2000. Methods and population. A two stage cluster sample of children attending group day care or cared for by a child minder was selected. Nasopharyngeal samples were cultured for SP and HI. Penicillin susceptibility was tested by disk diffusion and E-test and beta-lactamase production. Results. We sampled 235 children in the CM group and 298 in the GDC group who were ages 6 to 36 months. Age and sex distribution were similar in both groups. S. pneumoniae was isolated in 80 children in the CM group (34.0%) and in 163 (54.7%) children in GDC (P < 10−6). Proportions of non-penicillin susceptible (NPSP) were 52.5 and 55.8%, respectively (P = 0.6). H. influenzae was present in 37.2% of children in GDC vs. 23.8% in the CM group (P < 0.001). Proportions of beta-lactamase-positive HI (HIBL+) were 40.2% vs. 46.4%, respectively (P = 0.4). Antibiotic exposure during the previous 3 months occurred in 41.3% of children in GDC and in 47.4% in the CM group (P = 0.16). There was no association between antibiotic use and carriage of NPSP or HIBL+ strains. Conclusion. SP and HI carriage rates were significantly lower among children in the CM group than in GDC. The proportion of NPSP and HIBL+ was similar in both groups, and comparable patterns of antibiotic use were observed. Continued efforts must concentrate on parental education and enforcement of recommendations for management of pediatric upper respiratory tract infections.

Antimicrobial lock therapy in central-line associated bloodstream infections: a systematic review

PurposeAntimicrobial lock therapy (ALT) seems a promising approach for treatment of central line associated bloodstream infections (CLABSI). The recent introduction of molecules such as daptomycin and tigecycline, alone or in combination with other molecules, improved chances of efficacy of ALT, due to their activity on the bacterial biofilm. Our aim was to review the literature concerning ALT for CLABSI, including data concerning novel molecules.MethodsWe included case-control studies evaluating two or more molecules as ALT in central venous catheter infections extracted from the Medline database. Among 221 available articles in Pubmed, 54 were selected for their particular interest concerning ALT.ResultsIncidence of CLABSI is high worldwide. Mechanisms of catheter infection include contamination by skin bacteria, hand contamination and hematogenous diffusion. Catheter-infection is associated with biofilm formation, which reduces the efficacy of ALT. The most promising situation for ALT to succeed in salvaging a catheter appears to be coagulase-negative Staphylococcus infection, which is the main causative agent of CLABSI. Daptomycin, Tigecycline, Ethanol and Taurolidine appear as the best options for treating CLABSI; data are mostly available for Daptomycin, which showed, alone or associated with Rifampin, good in vitro potency on biofilm, but few in vivo data exist on efficacy.ConclusionsThe introduction of novel molecules has increased chances of catheter salvage with ALT in case of CLABSI, but further in vivo studies are needed.

In Vivo Comparative Pharmacokinetics and Pharmacodynamics of Moxifloxacin and Levofloxacin in Human Neutrophils

AbstractObjective: Most of the newer fluoroquinolones are active against bacteria such as Streptococcus pneumoniae and Staphylococcus aureus, which are able to multiply inside polymorphonuclear leukocytes (PMNs). The aim of this study was to determine moxifloxacin and levofloxacin intracellular behaviour with their usual dosage regimen. Methods: We determined the pharmacokinetics of moxifloxacin and levofloxacin at steady state in the PMNs of ten healthy volunteers receiving moxifloxacin 400mg and levofloxacin 500mg as a once-daily dosing regimen for 3 days. Results: Both antibacterials showed a high level of intracellular penetration exhibiting PMNs/plasma ratios of 17.34 ± 8.29 for moxifloxacin versus 8.15 ± 5.23 for levofloxacin for maximum concentrations (Cmax) and 14.72 ± 8.29 for moxifloxacin versus 8.15 ± 5.23 for levofloxacin for the area under the plasma concentration-time curve. Estimation of the most predictive pharmacodynamic surrogate markers for concentration-dependent bactericidal antibacterials in the intracellular milieu by taking into account the susceptibility of S. pneumoniae and methicillin-susceptible S. aureus demonstrated consistently higher values with moxifloxacin than with levofloxacin, even though with both drugs the levels obtained are well above the recommended targets values. Indeed, Cmax/MIC ratios calculated in PMNs for moxifloxacin were 287.3 and 718.2 for S. pneumoniae and S. aureus, respectively, and for levofloxacin were 25.6 and 205.1, respectively. Conclusion: Moxifloxacin and levofloxacin seem to be well adapted for the treatment of infections due to susceptible intracellular bacteria, and moxifloxacin provides a greater margin of safety than levofloxacin.

Impact of the 13-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of Streptococcus pneumoniae among children attending group daycare in southeastern France.

Regular surveys of pneumococcal nasopharyngeal carriage have been conducted among children attending daycare centers in Southeastern France from 1999 to 2012. We compared carriage rate, susceptibility patterns and serotype distribution in 2012, following implementation of the 13-valent pneumococcal conjugate vaccine, with findings from 5 previous surveys. Carriage rate was stable, antibiotic susceptibility improved and only serotype 19A persisted among vaccine-types.

New Perspectives Offered by a French Study of Antibiotic Resistance in Day-Care Centers

To provide ongoing information on regional trends of antibiotic resistance prevalence to pneumococci, a cross-sectional survey was conducted on a large representative sample of children attending day-care centers. Children were analyzed in spring (n = 379) and autumn (n = 379) for nasopharyngeal carriage. Streptococcus pneumoniae was detected in 149 children (39.4%) in spring and 204 (59.8%) in autumn. Half of these isolated strains showed penicillin insensitivity or resistance. A high proportion of children (43.6% in spring and 47.5% in autumn) had been treated with antibiotics during the 3 months prior to sample collection; 21.6% of isolated strains were serotype 6B, 20.1% type 23F, 18.9% type 19A and 19F, 11.5% type 14. Reduced susceptibility was frequently noted in serotype 23F, 14 and 9V, representing 93, 94 and 83% of identified serotypes, respectively. This type of survey on children in day-care centers can contribute to the understanding of regional variations in antibiotic resistance and provide information for epidemiological surveillance.

Virologically suppressed patients with asymptomatic and symptomatic HIV‐associated neurocognitive disorders do not display the same pattern of immune activation

Inversion of the CD4:CD8 ratio is a marker of immune activation and age‐associated disease. We measured the CD4:CD8 ratio as a marker of cognitive impairment in HIV‐infected patients and explored differences according to clinical severity.

Investigating the completeness of a histopathological cancer registry: Estimation by capture–recapture analysis in a French geographical unit Alpes-Maritimes, 2008

INTRODUCTION Cancer population studies require reliable and complete baseline data, which should theoretically be available by collecting histopathology records. The completeness of such a collection was evaluated using capture-recapture analysis based on three data sources concerning breast and colorectal cancers over an identical period and within the same geographical area. METHOD The total number of breast and colon cancer cases was estimated using capture-recapture analysis based on the number of cases which were common or not between sources recording screened, diagnosed and treated cancers in the French Alpes Maritimes district. RESULT The estimated total number of new cases of breast cancer diagnosed among Alpes Maritimes residents women aged 50-75 was 791 (95% CI: 784-797) in 2008. Of these 791 cases, 729 were identified through histopathology records, thus amounting to 92.2% completeness (95% CI: 91.5-93.0%). The total estimated number of new cases of colorectal cancer diagnosed among Alpes Maritimes residents aged 50-75 was 527 (95% CI: 517-536). Of these 527 cases, 481 were identified through histopathology records, thus amounting to 91.3% completeness (95% CI: 89.7-93.0%). CONCLUSION The estimated completeness of cancer records collected from histopathology laboratories was higher than 90% for new cases of breast and colorectal cancer within the age range concerned by the screening programme. A verified and validated histopathology data collection may be useful for cancer population studies.