Imported episodic rabies increases patient demand for and physician delivery of antirabies prophylaxis.

BACKGROUND: Imported cases threaten rabies reemergence in rabies-free areas. During 2000-2005, five dog and one human rabies cases were imported into France, a rabies-free country since 2001. The Summer 2004 event led to unprecedented media warnings by the French Public Health Director. We investigated medical practice evolution following the official elimination of rabies in 2001; impact of subsequent episodic rabies importations and national newspaper coverage on demand for and delivery of antirabies prophylaxis; regular transmission of epidemiological developments within the French Antirabies Medical Center (ARMC) network; and ARMC discussions on indications of rabies post-exposure prophylaxis (RPEP). METHODOLOGY/PRINCIPAL FINDINGS: Annual data collected by the National Reference Center for Rabies NRCR (1989-2006) and the exhaustive database (2000-2005) of 56 ARMC were analyzed. Weekly numbers of patients consulting at ARMC and their RPEP- and antirabies-immunoglobulin (ARIG) prescription rates were determined. Autoregressive integrated moving-average modeling and regression with autocorrelated errors were applied to examine how 2000-2005 episodic rabies events and their related national newspaper coverage affected demand for and delivery of RPEP. A slight, continuous decline of rabies-dedicated public health facility attendance was observed from 2000 to 2004. Then, during the Summer 2004 event, patient consultations and RPEP and ARIG prescriptions increased by 84%, 19.7% and 43.4%, respectively. Moreover, elevated medical resource use persisted in 2005, despite communication efforts, without any secondary human or animal case. CONCLUSIONS: Our findings demonstrated appropriate responsiveness to reemerging rabies cases and effective newspaper reporting, as no secondary case occurred. However, the ensuing demand on medical resources had immediate and long-lasting effects on rabies-related public health resources and expenses. Henceforth, when facing such an event, decision-makers must anticipate the broad impact of their media communications to counter the emerging risk on maintaining an optimal public health organization and implement a post-crisis communication strategy.

Organic and conventional fruits and vegetables contain equivalent counts of Gram-negative bacteria expressing resistance to antibacterial agents.

Resistance to antibiotics is a major public health problem which might culminate in outbreaks caused by pathogenic bacteria untreatable by known antibiotics. Most of the genes conferring resistance are acquired horizontally from already resistant commensal or environmental bacteria. Food contamination by resistant bacteria might be a significant source of resistance genes for human bacteria but has never been precisely assessed, nor is it known whether organic products differ in this respect from conventionally produced products. We showed here, on a large year-long constructed sample set containing 399 products that, irrespective of their mode of production, raw fruits and vegetables are heavily contaminated by Gram-negative bacteria (GNB) resistant to multiple antibiotics. Most of these bacteria originate in the soil and environment. We focused on non-oxidative GNB resistant to third-generation cephalosporins, because of their potential impact on human health. Among them, species potentially pathogenic for immunocompetent hosts were rare. Of the products tested, 13% carried bacteria producing extended-spectrum beta-lactamases, all identified as Rahnella sp. which grouped into two phylotypes and all carrying the bla(RAHN) gene. Thus, both organic and conventional fruits and vegetables may constitute significant sources of resistant bacteria and of resistance genes.

Integrons and antibiotic resistance in phylogenetic group B2 Escherichia coli.

It has been reported that Escherichia coli B2 phylogenetic group strains are more susceptible to antibiotics, especially to quinolones, and tend to carry less integrons than other phylogenetic groups in commensal environments. To gain a better understanding of the relationships between antibiotic resistance, integrons, and phylogenetic groups in an environment with high antibiotic selective pressure, we compared these characteristics in three selected groups of urinary tract infection E. coli isolated in a university hospital (G1, G2, and G3). The isolates were fully susceptible to antibiotics, resistant to amoxicillin and cotrimoxazol, or resistant to amoxicillin, cotrimoxazol, and nalidixic acid in the G1, G2, and G3 group, respectively. The prevalence of B2 isolates was significantly lower in the most resistant G3 group (22.6%) than in susceptible G1 (57.8%, p < 0.001) and G2 groups (50%, p < 0.01). In contrast, the prevalence of B2 isolates was not significantly different between G1 and G2 groups. The prevalence of integrons was nil in G1 isolates but very high in G2 (94.3%) and G3 (87.5%) isolates, and integrons were equally distributed among the phylogenetic groups. We propose a step-by-step mechanism for the emergence of antibiotic resistance in E. coli. Under very low selective pressure, resistance emerges without integrons. When the antibiotic pressure increases, quinolone and integron-mediated resistance occurs outside phylogenetic group B2. With strong antibiotic selective pressure, integrons are highly prevalent and widespread regardless of the phylogenetic group.

Effect of mutator P. aeruginosa on antibiotic resistance acquisition and respiratory function in cystic fibrosis.

BACKGROUND: Cystic fibrosis patients suffer from recurrent bacterial infections that result in progressive deterioration of their respiratory function. Despite intensive antibiotic treatment, Pseudomonas aeruginosa is the main cause of such infections, with clones progressively developing multiple antibiotic resistance. We determined the relationship between the presence of P. aeruginosa mutator strains and cystic fibrosis clinical characteristics. METHODS: We analyzed 136 strains of P. aeruginosa isolated from the expectorations of 36 CF patients. On all strains, mutation frequencies were determined by the mutation rate to rifampicin, and antibiotic susceptibility was determined by the disk diffusion method. The epidemiological relatedness of these 136 P. aeruginosa strains was studied by pulsed-field gel electrophoresis. The appearance of new antibiotic resistance by sequential analysis of genotypically identical strains was determined. Lung function test results, that is, forced expiratory volume in 1 sec and vital capacity, were also recorded from these patients. RESULTS: We showed that bacteria with an enhanced mutation rate increase the rate of acquisition of new antibiotic resistance threefold and are associated with the deterioration of lung function. CONCLUSIONS: This study demonstrates the effect of mutator bacteria on the efficiency of patient treatment and on their respiratory function. Given the consequence of antibiotic treatment failure and lung deterioration on the prognosis of CF patients, antibiotic treatment strategies may need to be optimized to prevent the emergence of mutator clones.

Antibodies to tetanus, diphtheria and pertussis among healthy adults vaccinated according to the French vaccination recommendations.

In this sero-epidemiological study, we investigated humoral immunity to three vaccine-preventable diseases--tetanus, diphtheria and pertussis--among 331 adults (aged 18-60 years) attending vaccination centres for travellers and who had been vaccinated according to national recommendations in France. Serological results showed that the percentage of subjects with antibodies to diphtheria and tetanus decreases with age. Results also confirmed surveillance data on vaccination in France, with 7.6% of the study population (13.4% of those aged 18-29 years) having recently acquired a pertussis infection. These results confirm the importance of following French recommendations for regular boosters for tetanus and diphtheria among adults. They also indicate the need for better implementation of the current recommendations for pertussis-vaccine boosters in adults.

Clonal population of flucytosine-resistant Candida tropicalis from blood cultures, Paris, France.

Candida tropicalis is a diploid ascomycetes yeast responsible for 4%-24% of candidemia. Resistance to flucytosine is rarely described for this species but was observed for 45 (35%) of 130 C. tropicalis isolates recovered from blood cultures in the Paris area in a 4-year survey. The aims of this study were to test the hypothesis that the flucytosine-resistant isolates could represent a subgroup and to determine the relationship between epidemiologic and genomic data. Epidemiologic data and gene sequences were analyzed, and molecular typing was performed. Our results suggest that a clone of flucytosine-resistant isolates, associated with malignancies and a lower mortality than that for other C. tropicalis isolates, is widespread in the Paris area. We propose the analysis of 2 polymorphic microsatellite markers coupled with URA3 sequencing to track the clone.

Antibiotics for nasopharyngitis are associated with a lower risk of office-based physician visit for acute otitis media within 14 days for 3- to 6-year-old children.

OBJECTIVES: This study was designed to analyse factors potentially influencing children's return visits to physicians for symptoms of acute otitis media (AOM) within 14 days after being diagnosed with nasopharyngitis (NP), and the impact of recent antibiotic use. DESIGN: A controlled population-based pharmaco-epidemiological trial in 3- to 6-year-old children conducted from January to May 2000. SETTING: Three different geographical regions in France. PARTICIPANTS: Among 2507 eligible children, 2456 could be analysed and 505 children had 634 office-based physician visits (OBPV) for NP symptoms. INTERVENTIONS: The statistical associations between antibiotics prescribed for NP and an OBPV for AOM within 14 days in a population-based study were analysed along with risk factors of AOM. MAIN OUTCOMES MEASURE: Clinical events and antibiotic use. RESULTS: During the 2 weeks following physician-diagnosed NP, antibiotic use, especially a beta-lactam, significantly decreased the risk of OBPV for AOM in children (odds ratio=0.2; 95% confidence interval=0.09-0.7; P=0.002). CONCLUSION: Antibiotics prescribed to children for NP seem to protect during the following 2 weeks against the risk of OBPV for AOM. It remains to be determined whether a subgroup at high risk of developing AOM after a viral infection exists and what might be the best strategy to adopt for NP in a national programme of optimal antibiotic use.

Primary and opportunistic pathogens associated with meningitis in adults in Bangui, Central African Republic, in relation to human immunodeficiency virus serostatus.

OBJECTIVE: To determine the causative organisms and characteristics of patients presenting with meningitis in Bangui in order to provide guidance to physicians for case management. METHODS: Adults with proven or suspected meningitis were enrolled in this prospective study. LABORATORY TESTS: Full blood count, blood chemistry, and HIV tests were performed. Cerebrospinal fluid (CSF) was submitted for routine microbiology, chemistry (glucose, protein), and hematology testing. When classical microbiology analyses were negative, a broad-range bacterial polymerase chain reaction (BRBPCR) was used. RESULTS AND CONCLUSIONS: Of the 276 patients enrolled, 215 (77.9%) were HIV positive. In HIV-positive patients cryptococcal meningitis (CM) was the most common cause of meningitis (39.1%) followed by pyogenic meningitis (PM) (30.7%), mononuclear meningitis (MM) (28.8%), and tuberculous meningitis (TM) (1.4%). In HIV-negative patients, PM was the most common cause (60.7%) followed by MM (37.7%) and CM (1.6%, one case). In-hospital mortality was higher in HIV-positive patients (73/128 = 57%) compared to those HIV negative (3/18 = 16.7%) (p = 0.001). Streptococcus pneumoniae (n = 26) was the most common bacterial diagnosis, mainly in HIV-positive patients (n = 22, 10.2%). Meningococcal meningitis (14 Neisseria meningitidis of group A and one W135) was diagnosed in nine (4.2%) HIV-positive and six (9.8%) HIV-negative patients. Gram-negative rods were isolated from five HIV-positive and two HIV-negative patients, respectively. The bacteria and fungi involved in meningitis did not display high levels of in vitro resistance. Conventional microbiology techniques failed to detect the causative agent in 55 (53.4%) PM cases. Broad-range bacterial PCR detected DNA from S. pneumoniae in three samples, N. meningitidis in two, Escherichia coli in one, Listeria monocytogenes in two and Staphylococcus aureus in one sample. In the CSF of five (three HIV negative and two HIV positive), PCR products were not identified with the oligonucleotide probes specific for the usual species of bacteria found in CSF, or genera commonly considered potential contaminants of clinical samples. Among the MM cases, 77 (90.5%) probable viral meningitis (54 HIV positive and 23 HIV negative) and eight TM (HIV positive) were suspected.

Reduction of antibiotic use in the community reduces the rate of colonization with penicillin G-nonsusceptible Streptococcus pneumoniae.

BACKGROUND: There is a lack of evidence documenting the impact of optimized antibiotic use on the rates of colonization with penicillin G-nonsusceptible Streptococcus pneumoniae (PNSP) in children. This study evaluates the effect of community-based intervention strategies on the prevalence of pnsp colonization. METHODS: A controlled, population-based pharmacoepidemiological trial was conducted from January through May 2000. Three French geographic areas were selected on the basis of demographic similarities. Two intervention strategies were implemented: (1) reduced antibiotic use, which was achieved by not prescribing antibiotics for presumed viral respiratory tract infections (the prescription-reduction group); and (2) better adaptation of dose and duration (the dose/duration group). A control group received no intervention. The target population was children aged 3-6 years who were attending kindergarten. Oropharyngeal pneumococcus colonization and antibiotic use were monitored throughout the 5-month study. RESULTS: The prescription-reduction, dose/duration, and control groups included 601, 483, and 405 children, respectively. The interventions induced significantly larger decreases in antibiotic use in the prescription-reduction group (-18.8%) and dose/duration group (-17.1%) than in the control group (-3.8%), and the rates of PNSP colonization were initially similar for the 3 groups (52.5%, 55.1%, and 50.0%, respectively). At the end of the 5-month study, the rates of PNSP colonization were 34.5% for the prescription-reduction group (P=.05) and 44.3% for the dose/duration group (P=.8), compared with 46.2% for the control group. CONCLUSIONS: Intensive educational strategies aimed at optimizing antibiotic use can significantly reduce the rate of PNSP colonization in areas with high resistance rates.

Measurement of immunoglobulin G against Mycobacterial antigen A60 in patients with cystic fibrosis and lung infection due to Mycobacterium abscessus.

BACKGROUND: The diagnosis and prognosis of lung infections due to the emerging nontuberculous mycobacterium (NTM) Mycobacterium abscessus are difficult to establish in children with cystic fibrosis. METHODS: We evaluated the usefulness of an enzyme-linked immunosorbent assay for detecting serum IgG antibodies against the ubiquitous mycobacterial antigen A60. RESULTS: A total of 186 patients with cystic fibrosis (mean age+/-SD, 12.0+/-5.0 years) were studied, including 15 M. abscessus-positive patients who fulfilled American Thoracic Society (ATS) criteria for NTM infection (M. abscessus-infected patients), 7 M. abscessus-positive patients who did not fulfill ATS criteria, 20 patients positive for various other NTM who did not fulfill ATS criteria, and 144 NTM-negative control patients; mean IgG titers (+/-SD) for these 4 groups were 718+/-342 U, 193+/-113 U, 129+/-49 U, and 121+/-53 U, respectively (M. abscessus-infected patients vs. each of the other groups, P<.005). The A60 IgG test was both sensitive (approximately 87%) and specific (approximately 95%) if adapted cutoff values were used (150 U and 250 U for patients aged 10 years, respectively) and correlated well with results of acid-fast bacilli smears. CONCLUSION: Measurement of anti-A60 IgG may be useful for both the diagnosis and assessment of activity of M. abscessus lung infection in persons with cystic fibrosis.

No significant decrease in antibiotic use from 1992 to 2000, in the French community.

OBJECTIVES: To analyse trends in antibiotic exposure of the French population from 1992 to 2000. METHODS: The analysis used data provided by a representative annual nationwide survey of health care consumption in the community. RESULTS: The frequency of antibiotic use increased from 4.7 per 100 person-months in 1992 to 7.3 in 1995, and remained stable from 1998 to 2000. Children under 7 years of age were three times more strongly exposed to antibiotics than older subjects. Respiratory tract infections of probable viral aetiology and sore throat accounted for >50% of antibacterial prescriptions. CONCLUSIONS: We identified two major priorities for campaigns designed to reduce antibiotic exposure of the French population in the community, namely respiratory tract infections of presumed viral origin, and children under 7 years of age.