Decline in antibiotic resistance and changes in the serotype distribution of Streptococcus pneumoniae isolates from children with acute otitis media; a 2001-2011 survey by the French Pneumococcal Network.

Streptococcus pneumoniae is an important cause of acute otitis media (AOM). The aim of this study was to evaluate trends in antibiotic resistance and circulating serotypes of pneumococci isolated from middle ear fluid of French children with AOM during the period 2001-2011, before and after the introduction of the PCV-7 (2003) and PCV-13 (2010) vaccines. Between 2001 and 2011 the French pneumococcal surveillance network analysed the antibiotic susceptibility of 6683 S. pneumoniae isolated from children with AOM, of which 1569 were serotyped. We observed a significant overall increase in antibiotic susceptibility. Respective resistance (I+R) rates in 2001 and 2011 were 76.9% and 57.3% for penicillin, 43.0% and 29.8% for amoxicillin, and 28.6% and 13.0% for cefotaxime. We also found a marked reduction in vaccine serotypes after PCV-7 implementation, from 63.0% in 2001 to 13.2% in 2011, while the incidence of the additional six serotypes included in PCV-13 increased during the same period, with a particularly high proportion of 19A isolates. The proportion of some non-PCV-13 serotypes also increased between 2001 and 2011, especially 15A and 23A. Before PCV-7 implementation, most (70.8%) penicillin non-susceptible pneumococci belonged to PCV-7 serotypes, whereas in 2011, 56.8% of penicillin non-susceptible pneumococci belonged to serotype 19A. Between 2001 and 2011, antibiotic resistance among pneumococci responsible for AOM in France fell markedly, and PCV-7 serotypes were replaced by non-PCV-7 serotypes, especially 19A. We are continuing to assess the impact of PCV-13, introduced in France in 2010, on pneumococcal serotype circulation and antibiotic resistance.

Impact of the pneumococcal conjugate vaccines on invasive pneumococcal disease in France, 2001-2012.

CONTEXT AND AIMS: Vaccination with the 7-valent pneumococcal conjugate vaccine (PCV7) was recommended in France in 2003 for children <2 years. The 13-valent conjugate vaccine (PCV13) replaced PCV7 in 2010. We assessed the impact of PCVs vaccination on the incidence of invasive pneumococcal diseases (IPD) in French children (0-15 years) and adults (>15 years). METHODS: IPD rates were calculated using cases reported from 2001 to 2012 to Epibac, a laboratory network. The distribution of serotypes was assessed from invasive isolates serotyped at the National reference Centre for Pneumococci. IPD incidence rates were compared between the pre-PCV7 (2001-2002), late PCV7 (2008-2009) and post PCV13 (2012) periods. RESULTS: The PCVs coverage increased from 56% in the 2004 birth-cohort to 94% in the 2008 and following birth-cohorts. Following PCV7 introduction, IPD incidence decreased by 19% between 2001-2002 and 2008-2009 in children <2 years, but increased in children aged 2-15 years and adults, despite a sharp decline in PCV7-IPD in all age-groups. After PCV13 introduction, IPD incidence decreased by 34% in children <5 years, by 50% in those aged 5-15 years and 15% in adults from 2008-2009 to 2012. The incidence of PCV13-Non PCV7-IPD decreased by 74% in children <5 years and by 60% in those aged 5-15 years. CONCLUSIONS: Vaccination with PCV13 was rapidly followed by a decrease in the incidence of all-type IPD in children, in relation with a sharp decrease in the incidence of PCV13-Non PCV7-IPD. Moreover, all-type IPD decreased after PCV13 introduction in older non-vaccinated age-groups, with a shift in the distribution of serotypes. Considering the whole 2001-2012 period, the vaccination with PCV7 and PCV13 resulted in a decline in the incidence of IPD in children up to the age of 5 but not in older children and adults.

Assessment of five screening strategies for optimal detection of carriers of third-generation cephalosporin-resistant Enterobacteriaceae in intensive care units using daily sampling.

There is no consensus on optimal screening procedures for multidrug-resistant Enterobacteriaceae (MDRE) in intensive care units (ICUs). Therefore, we assessed five strategies for the detection of extended-spectrum beta-lactamase (ESBL) and high-level expressed AmpC cephalosporinase (HL-CASE) producers. During a 3-month period, a rectal screening swab sample was collected daily from every ICU patient, from the first 24 h to the last day of ICU stay. Samples were plated on MDRE-selective media. Bacteria were identified using MALDI-TOF mass spectrometry and antibiograms were performed using disk diffusion. MDREs were isolated from 682/2348 (29.0%) screening samples collected from 93/269 (34.6%) patients. Incidences of patients with ESBL and HL-CASE producers were 17.8 and 19.3 per 100 admissions, respectively. In 48/93 patients, MDRE carriage was intermittent. Compared with systematic screening at admission, systematic screening at discharge did not significantly increase the rate of MDRE detection among the 93 patients (62% vs. 70%). In contrast, screening at admission and discharge, screening at admission and weekly thereafter, and screening at admission and weekly thereafter and at discharge significantly increased MDRE detection (77%, p 0.02; 76%, p 0.01; 86%, p<0.001, respectively). The difference in MDRE detection between these strategies relies essentially on the levels of detection of patients with HL-CASE producers. The most reasonable strategy would be to collect two samples, one at admission and one at discharge, which would detect 87.5% of the ESBL strains, 67.3% of the HL-CASE strains and 77.4% of all MDRE strains. This study should facilitate decision-making concerning the most suitable screening policy for MDRE detection in a given ICU setting.

Resistance exercise training modulates acute gene expression during human skeletal muscle hypertrophy.

We sought to determine whether acute resistance exercise (RE)-induced gene expression is modified by RE training. We studied the expression patterns of a select group of genes following an acute bout of RE in naïve and hypertrophying muscle. Thirteen untrained subjects underwent supervised RE training for 12 wk of the nondominant arm and performed an acute bout of RE 1 wk after the last bout of the training program (training+acute). The dominant arm was either unexercised (control) or subjected to the same acute exercise bout as the trained arm (acute RE). Following training, men (14.8 ± 2.8%; P < 0.05) and women (12.6 ± 2.4%; P < 0.05) underwent muscle hypertrophy with increases in dynamic strength in the trained arm (48.2 ± 5.4% and 72.1 ± 9.1%, respectively; P < 0.01). RE training resulted in attenuated anabolic signaling as reflected by a reduction in rpS6 phosphorylation following acute RE. Changes in mRNA levels of genes involved in hypertrophic growth, protein degradation, angiogenesis, and metabolism commonly expressed in both men and women was determined 4 h following acute RE. We show that RE training can modify acute RE-induced gene expression in a divergent and gene-specific manner even in genes belonging to the same ontology. Changes in gene expression following acute RE are multidimensional, and may not necessarily reflect the actual adaptive response taking place during the training process. Thus RE training can selectively modify the acute response to RE, thereby challenging the use of gene expression as a marker of exercise-induced adaptations.

Fighting the spread of AmpC-hyperproducing Enterobacteriaceae: beneficial effect of replacing ceftriaxone with cefotaxime.

OBJECTIVES: Considering the hypothesis that the high biliary elimination of ceftriaxone could be responsible for the selection of Enterobacteriaceae harbouring high-level AmpC ß-lactamase (HL-CASE), the use of ceftriaxone was discontinued in our hospital in 2006 and replaced with cefotaxime. METHODS: Antibiotic consumption, expressed as defined daily dose (DDD)/1000 patient-days (PD), and HL-CASE incidence, expressed as the number of patients carrying HL-CASE/1000 PD, were compared between the pre-intervention period (Period 1, 2001-05) and the post-intervention period (Period 2, 2006-12) using an interrupted time series analysis. RESULTS: The incidence of HL-CASE increased significantly from 0.32 to 0.69/1000 PD during Period 1 (coefficient = 0.082, P < 0.01). A significant inflection of the slope in the incidence curve occurred in Period 2 (coefficient = -0.061, P = 0.05), mainly owing to the stabilization of the HL-CASE incidence of Enterobacteriaceae harbouring chromosomally inducible cephalosporinase (Period 1, 0.27 to 0.64/1000 PD; Period 2, 0.58 to 0.61/1000 PD) and especially for Enterobacter cloacae (Period 1, 0.09 to 0.30/1000 PD; Period 2, 0.26 to 0.27/1000 PD). This deceleration was observed despite a significant increase in the slope of cefotaxime consumption over Period 2 (coefficient = 2.97, P < 0.01). CONCLUSION: Despite the disadvantages of using cefotaxime compared with ceftriaxone (administration three times daily versus once a day), the ecological benefits of this substitution seem sufficiently convincing to preferentially use cefotaxime. Control of HL-CASE incidence is crucial to limiting carbapenem use and preventing the selection of carbapenemase-producing Enterobacteriaceae.

In vitro activity of cefoxitin and imipenem against Mycobacterium abscessus complex.

The in vitro activity of cefoxitin and imipenem was compared for 43 strains of the Mycobacterium abscessus complex, mostly isolated from cystic fibrosis patients. The MICs of imipenem were lower than those of cefoxitin, although the number of imipenem-resistant strains was higher according to the CLSI breakpoints. Strain comparisons indicated that the MICs of cefoxitin were significantly higher for Mycobacterium bolletii than for M. abscessus. The MICs of both ß-lactams were higher for the rough morphotype than for the smooth morphotype. The clinical impact of the in vitro difference between the activity of imipenem and that of cefoxitin remains to be determined.

Comparison of five media for detection of extended-spectrum Beta-lactamase by use of the wasp instrument for automated specimen processing.

Overall, 2,337 rectal screening samples (RSSs) were seeded by using the Wasp instrument for automated microbiological processing with five media for detection of extended-spectrum ß-lactamase (ESBL): CHROMagar, ChromID, Brilliance, BD Drigalski, and HEGP media. Of 354 RSSs harboring ESBL-producing isolates, 89.3% were found to be positive on all media. Sensitivity and specificity ranged from 95.5 to 98.3% and from 57.9 to 72.3%, respectively. No medium was perfectly ESBL selective, and non-ESBL-producing strains were mainly Enterobacteriaceae overproducing AmpC ß-lactamase and nonfermenting Gram-negative bacilli, mostly Pseudomonas aeruginosa.

Readmission of known MRSA carriers and MRSA colonization pressure in hospital.

Readmission of asymptomatic methicillin-resistant Staphylococcus aureus (MRSA) carriers may contribute to the hospital reservoir. Using an electronic alert system, we assessed the weight of readmission of known MRSA carriers on MRSA colonization pressure in a hospital setting. During the 2004-2010 period, 2058 alerts were generated for 1060 inpatients. A total of 486/1060 patients (46%) were readmitted at least once, and 330/486 (64·4%) were readmitted <3 months after discharge. A mean of 20 MRSA patients were present on the same day (from 40 in 2004 to eight in 2010). The number of MRSA patient-days was 34 575, i.e. 2·5% of the 1 366 277 patient-days of the study period, and 17 737 (51·3%) MRSA patient-days were due to readmission of known MRSA carriers. The number of new MRSA cases was partly correlated with the number of MRSA patients hospitalized (R 2 = 0·49). Rapid electronic identification of these patients proved essential in decreasing the global burden of MRSA in our hospital.

Differences in daptomycin and vancomycin ex vivo behaviour can lead to false interpretation of negative blood cultures.

In clinical studies on bacteraemia, the negativity of blood cultures is an important endpoint for comparing the efficacy of different therapeutic regimens. In FAN anaerobic blood culture medium (BacT/ALERT system), daptomycin displayed increased MIC against Staphylococcus aureus and improved abolishment of its carryover effect in charcoal when compared with vancomycin. Differences between these two drugs can lead to a false interpretation of negative blood cultures. To compare different antibiotic regimens for the treatment of bacteraemia, preliminary studies are mandatory to ensure that ex vivo antibiotic behaviour is similar in the blood-culture system used.

Do clinicians consider the results of the BinaxNOW Streptococcus pneumoniae urinary antigen test when adapting antibiotic regimens for pneumonia patients?

The BinaxNOW Streptococcus pneumoniae urinary antigen test is a rapid and reliable immunochromatographic test (ICT) for the identification of a pneumococcal aetiology of pneumonia. The aim of this study was to evaluate the attitude of clinicians in their everyday practice towards prescription of the ICT and the impact of its results on the adaptation of the antibiotic therapy when pneumonia is suspected. From October 2007 to March 2008, we prospectively evaluated 541 consecutive inpatients for whom the ICT was performed in our institution. Of the 541 patients evaluated, only 233 (43%) were suspected by the treating physicians to have a pneumonia, 58 of whom had a positive ICT result. Among these 58 patients, four (7%) and 26 (45%), respectively, were treated with amoxycillin monotherapy before and after the ICT result had been obtained (p <10(-4)). Although a positive ICT result led to a rise in the proportion of patients treated with amoxycillin alone, a large number continued to be treated with broader-spectrum antibiotics. These results suggest that prescription monitoring of the ICT should be implemented along with encouragement to adhere more strictly to treatment guidelines.

Boosting enrollment in neurology trials with Local Identification and Outreach Networks (LIONs).

OBJECTIVE: Our purpose was to develop a geographically localized, multi-institution strategy for improving enrolment in a trial of secondary stroke prevention. METHODS: We invited 11 Connecticut hospitals to participate in a project named the Local Identification and Outreach Network (LION). Each hospital provided the names of patients with stroke or TIA, identified from electronic admission or discharge logs, to researchers at a central coordinating center. After obtaining permission from personal physicians, researchers contacted each patient to describe the study, screen for eligibility, and set up a home visit for consent. Researchers traveled throughout the state to enroll and follow participants. Outside the LION, investigators identified trial participants using conventional recruitment strategies. We compared recruitment success for the LION and other sites using data from January 1, 2005, through June 30, 2007. RESULTS: The average monthly randomization rate from the LION was 4.0 participants, compared with 0.46 at 104 other Insulin Resistance Intervention after Stroke (IRIS) sites. The LION randomized on average 1.52/1,000 beds/month, compared with 0.76/1,000 beds/month at other IRIS sites (p = 0.03). The average cost to randomize and follow one participant was $8,697 for the LION, compared with $7,198 for other sites. CONCLUSION: A geographically based network of institutions, served by a central coordinating center, randomized substantially more patients per month compared with sites outside of the network. The high enrollment rate was a result of surveillance at multiple institutions and greater productivity at each institution. Although the cost per patient was higher for the network, compared with nonnetwork sites, cost savings could result from more rapid completion of research.

Subcutaneous IGF-1 is not beneficial in 2-year ALS trial.

BACKGROUND: Previous human clinical trials of insulin-like growth factor type I (IGF-1) in amyotrophic lateral sclerosis (ALS) have been inconsistent. This phase III, randomized, double-blind, placebo-controlled study was undertaken to address whether IGF-1 benefited patients with ALS. METHODS: A total of 330 patients from 20 medical centers were randomized to receive 0.05 mg/kg body weight of human recombinant IGF-1 given subcutaneously twice daily or placebo for 2 years. The primary outcome measure was change in their manual muscle testing score. Secondary outcome measures included tracheostomy-free survival and rate of change in the revised ALS functional rating scale. Intention to treat analysis was used. RESULTS: There was no difference between treatment groups in the primary or secondary outcome measures after the 2-year treatment period. CONCLUSIONS: Insulin-like growth factor type I does not provide benefit for patients with amyotrophic lateral sclerosis.

Impact of infant pneumococcal vaccination on invasive pneumococcal diseases in France, 2001-2006.

Vaccination with the 7-valent pneumococcal conjugate vaccine (PCV) has been recommended in France since 2003 for children under the age of two years who are at risk due to medical or living conditions. From 2006, the recommendation has been extended to all children under two years. The impact of PCV introduction on the incidence of pneumococcal meningitis and bacteraemia and on the serotype distribution in French children and other age-groups was assessed using laboratory surveillance data. The coverage with three doses of PCV was 44% in children aged 6-12 months in 2006. From 2001/2002 to 2006, the incidence of pneumococcal meningitis decreased from 8.0 to 6.0 cases per 100,000, and the incidence of pneumococcal bacteraemia decreased from 21.8 to 17.5 cases per 100,000 in children under the age of two years. For the vaccine strains, the incidence of pneumococcal meningitis and bacteraemia decreased from 20,4 to 6.0 cases per 100,000, while the incidence of pneumococcal meningitis and bacteraemia due to non-vaccine strains increased from 9.4 to 17.5 cases per 100,000 in this time period. The incidence in older children and adults did not decrease. Further expansion of PCV coverage is expected to increase the impact of the vaccination in both children and adults. However, the fact that cases caused by vaccine serotypes have been partially substituted by cases of non-vaccine serotypes is likely to reduce the overall benefit of PCV in France, should this early observation be confirmed in the future.

Occurrence of qnrA-positive clinical isolates in French teaching hospitals during 2002-2005.

Bacteria harbouring the novel qnrA plasmid-mediated mechanism of quinolone resistance have been described in different countries, but the frequency of their occurrence has not been investigated. In total, 1,468 clinical isolates of Enterobacteriaceae with quinolone resistance or extended-spectrum beta-lactamase (ESBL) phenotypes were collected from eight teaching hospitals in France during 2002-2005 and screened for qnrA. Overall, 28 isolates (22 Enterobacter cloacae, three Klebsiella pneumoniae, one Citrobacter freundii, one Klebsiella oxytoca and one Proteus mirabilis) were positive for qnrA, representing 1.9% of all isolates, 3.3% of ESBL-producing isolates (22% of the E. cloacae isolates) and 0% of non-ESBL-producing isolates. The prevalence of qnrA among consecutive ESBL-producing isolates in 2004 from the eight hospitals was 2.8% (18/639). Of the qnrA-positive isolates, 100% were intermediately-resistant or resistant to nalidixic acid, and 75% to ciprofloxacin. Twenty-one of the 22 qnrA-positive E. cloacae isolates were obtained from two hospitals in the Paris area, and molecular typing and plasmid content analysis showed clonal relationships for five, three and two isolates, respectively. The qnrA genetic environment was similar to that of the In36 integron. The remaining two isolates had qnrA variants (30 and 29 nucleotide differences, respectively, compared with the original sequence) and an unknown genetic environment. The ESBL gene associated with qnrA was bla(SHV-12) in most of the isolates, but bla(PER-1) and bla(SHV-2a) were found in two isolates. In France, it appears that qnrA-positive isolates are predominantly E. cloacae isolates producing SHV-12, and may be associated with the dissemination of an In36-like integron.

Fulminant invasive pulmonary aspergillosis in immunocompetent patients--a two-case report.

Two cases of invasive aspergillosis (IA) in immunocompetent patients with a fulminant fatal outcome are reported. Both patients were elderly and had a history of chronic lung disease treated with prolonged inhaled corticosteroids and a short course of systemic corticosteroids. They presented with dyspnea and fever, their respiratory function deteriorated rapidly, and they died 7 days after admission. Aspergillus fumigatus was cultured from respiratory samples. IA was confirmed in one case by necropsy that showed diffuse bilateral necrotizing pneumonitis and myocarditis. In the other case, IA diagnosis was established by thoracic CT scan plus detection of Aspergillus antigen in two blood samples. These two cases demonstrate that short-term corticosteroid therapy in immunocompetent patients with underlying chronic lung conditions is a risk factor for IA, and that its evolution can be fulminant.

Persistent facial myokymia associated with K(+) channel antibodies.

A 58-year-old woman developed bilateral facial myokymia in 1978, persisting for the next 23 years and associated with high titers of voltage-gated K(+) channel (VGKC) antibodies. Brain imaging failed to show a pontine lesion. The clinical facial myokymia and electromyographic doublets and multiplets (43 to 250 Hz) were milder and more restricted than those seen in generalized neuromyotonic disorders with VGKC antibodies. This case and another reported recently represent a focal VGKC antibody syndrome.