Salbutamol use in relation to maintenance bronchodilator efficacy in COPD: a prospective subgroup analysis of the EMAX trial.

BACKGROUND: Short-acting ß2-agonist (SABA) bronchodilators help alleviate symptoms in chronic obstructive pulmonary disease (COPD) and may be a useful marker of symptom severity. This analysis investigated whether SABA use impacts treatment differences between maintenance dual- and mono-bronchodilators in patients with COPD. METHODS: The Early MAXimisation of bronchodilation for improving COPD stability (EMAX) trial randomised symptomatic patients with low exacerbation risk not receiving inhaled corticosteroids 1:1:1 to once-daily umeclidinium/vilanterol 62.5/25 µg, once-daily umeclidinium 62.5 µg or twice-daily salmeterol 50 µg for 24 weeks. Pre-specified subgroup analyses stratified patients by median baseline SABA use (low, < 1.5 puffs/day; high, ≥1.5 puffs/day) to examine change from baseline in trough forced expiratory volume in 1 s (FEV1), change in symptoms (Transition Dyspnoea Index [TDI], Evaluating Respiratory Symptoms-COPD [E-RS]), daily SABA use and exacerbation risk. A post hoc analysis used fractional polynomial modelling with continuous transformations of baseline SABA use covariates. RESULTS: At baseline, patients in the high SABA use subgroup (mean: 3.91 puffs/day, n = 1212) had more severe airflow limitation, were more symptomatic and had worse health status versus patients in the low SABA use subgroup (0.39 puffs/day, n = 1206). Patients treated with umeclidinium/vilanterol versus umeclidinium demonstrated statistically significant improvements in trough FEV1 at Week 24 in both SABA subgroups (59-74 mL; p < 0.001); however, only low SABA users demonstrated significant improvements in TDI (high: 0.27 [p = 0.241]; low: 0.49 [p = 0.025]) and E-RS (high: 0.48 [p = 0.138]; low: 0.60 [p = 0.034]) scores. By contrast, significant reductions in mean SABA puffs/day with umeclidinium/vilanterol versus umeclidinium were observed only in high SABA users (high: - 0.56 [p < 0.001]; low: - 0.10 [p = 0.132]). Similar findings were observed when comparing umeclidinium/vilanterol and salmeterol. Fractional polynomial modelling showed baseline SABA use ≥4 puffs/day resulted in smaller incremental symptom improvements with umeclidinium/vilanterol versus umeclidinium compared with baseline SABA use < 4 puffs/day. CONCLUSIONS: In high SABA users, there may be a smaller difference in treatment response between dual- and mono-bronchodilator therapy; the reasons for this require further investigation. SABA use may be a confounding factor in bronchodilator trials and in high SABA users; changes in SABA use may be considered a robust symptom outcome. FUNDING: GlaxoSmithKline (study number 201749 [NCT03034915]).

The impact of inhaler technique on clinical outcomes in adolescents and adults with asthma: A systematic review.

BACKGROUND: Many patients with asthma use their inhalers incorrectly, which can lead to sub-optimal asthma control and an increased risk of exacerbations. The Accuhaler/Diskus and Turbuhaler are arguably two of the most commonly used dry powder inhalers worldwide. METHODS: A systematic literature review (SLR) was conducted to assess the impact of inhalation errors with these dry powder inhalers on clinical outcomes in asthma. Database searches were conducted in MEDLINE, Embase and proceedings from scientific conferences. Observational studies in adults and adolescents with asthma, reporting data for Accuhaler/Diskus and Turbuhaler devices and at least one outcome of interest, were included. Dual-independent screening and validation of studies was performed. RESULTS: The search identified 35 studies. A range of inhaler errors was observed across studies and devices. In 8 out of the 9 studies that involved the two devices, the percentage of overall inhaler error rates was numerically (7 studies) or significantly (1 study) higher for Turbuhaler than Diskus, ranging from 3.7% to 71.9% for Diskus and 1.2%-83% for Turbuhaler. Critical errors, reported in three studies using similar definitions, ranged from 20% to 43% for Diskus and 32%-100% for Turbuhaler. Five studies reported a significant association between inhaler errors and worse asthma control, while one showed no difference. CONCLUSIONS: This SLR identified a large range of inhaler errors with both devices. Across devices, a better inhalation technique was associated with better asthma outcomes. This systematic review confirms the importance of patients using their inhalers correctly as an integral part of achieving optimal asthma outcomes.

[Asthma control level in asthmatic children followed in general practice medicine in France: results of ER'ASTHME study]. / Niveau de contrôle de l'asthme chez l'enfant en médecine générale en France: résultats de l'étude ER'ASTHME.

UNLABELLED: Little information is available on asthma control level in children in France in general practice medicine although such control is 1 of the essential goals of treatment. The ER'Asthme survey has been set up to assess asthma control among asthmatic patients visiting their general practitioner and to determine the clinical and therapeutic associated factors. METHODS: Cross-sectional ancillary study carried out in 1410 asthmatic children aged 6 to 14 years old (B/G 65/35%), with asthma diagnosed at least 12 months earlier and visiting spontaneously their GP. It collected data on self-assessed health status, asthma control (assessed by 3-level composite score based on the Canadian consensus criteria as adapted by Anaes: optimal, acceptable and unacceptable), and compliance (PMAQ3w questionnaire) during the last 4 weeks. RESULTS: Children (or their parents) answered the question about their asthma control as follow: 62% "excellent" or "fine", 31% "not very good" and 7% "poor". GPs, however, assessed asthma control as optimal in 27% of children, acceptable in 7% and unacceptable in 66%. Eighty-four per cent of children had taken a maintenance treatment. Only 57% of patients reported complete compliance with their maintenance treatment (60% in 6-12 years old vs 52% in 13-14 years old, P=0.0089). Asthma control level was significantly associated to the asthma severity (P=0.0063), type of maintenance treatment (P<0.0001) and to treatment compliance (P=0.0005). CONCLUSION: Asthmatic children aged 6 to 14 years old (or their parents) overestimate their asthma control, which remains inadequate. Severity of asthma, compliance level and the type of maintenance treatment influence the level of asthma control.

[Lung cancer in the elderly subject]. / Cancer bronchique du sujet âgé.

INTRODUCTION: In France, the average age for the diagnosis of bronchial carcinoma is 64. It is 76 in the population of over 70. In fact, its incidence increases with age linked intrinsic risk of developing a cancer and with general ageing of the population. Diagnosis tools are the same for elderlies than for younger patients, and positive diagnosis mainly depends on fibreoptic bronchoscopy, complications of which being comparable to those observed in younger patients. STATE OF THE ART: The assessment of dissemination has been modified in recent years by the availability of PET scanning which is increasingly becoming the examination of choice for preventing unnecessary surgical intervention, a fortiori in elderly subjects. Cerebral imaging by tomodensitometry and nuclear magnetic resonance should systematically be obtained before proposing chirurgical treatment. An assessment of the general state of health of the elderly subject is an essential step before the therapeutic decision is made. This depends on the concept of geriatric evaluation: Geriatric Multidimensional Assessment, and the Comprehensive Geriatric Assessment which concerns overall competence of the elderly. PERSPECTIVES: This is a global approach that allows precise definition and ranking of the patient's problems and their impact on daily life and social environment. Certain geriatric variables (IADL, BADL, MMSE, IMC etc) may be predictive of survival rates after chemotherapy or the incidence of complications following thoracic surgery. The main therapeutic principles for the management of bronchial carcinoma are applicable to the elderly subject; long term survival without relapse after surgical resection is independent of age. Whether the oncological strategy is curative or palliative, the elderly patient with bronchial carcinoma should receive supportive treatments. They should be integrated into a palliative programme if such is the case. In fact, age alone is not a factor that should detract from optimal oncological management. CONCLUSIONS: The development of an individual management programme for an elderly patient suffering from bronchial carcinoma should be based on the combination of oncological investigation and comprehensive geriatric assessment.

[Evaluation of pulmonary function in the elderly. Intergroupe Pneumo Gériatrie SPLF-SFGG]. / Evaluation de la fonction respiratoire chez le sujet âgé. Intergroupe Pneumo Gériatrie SPLF-SFGG.

Aging is associated with a progressive decrease in lung function. As a consequence of aging, individual's reserve is diminished, but this decrease is heterogeneous between individual subjects. Many factors are involved in the overall decline in lung function. The prevalence of asthma in the elderly is estimated between 6 and 10%. Mortality due to COPD is increasing, especially among older subjects. Older subjects are at an increased risk of developing chronic diseases such as Parkinson's disease, which can have consequences for lung function. Under-nutrition is also common in the elderly and can produce sarcopenia and skeletal muscle dysfunction. The presentation of respiratory disorders may differ in the elderly, especially because of a lack of perception of symptoms such as dyspnea. The impact of bronchodilatators or corticosteroids on respiratory function has not been studied in the elderly. Drugs usually used for the treatment of hypertension or arrhythmias, which are often observed with aging, can have pulmonary toxicity. There is no difference between functional evaluation in younger and older subjects but it is more difficult to find predicted values for older patients. Performing pulmonary function tests in older patients is often difficult because of a higher prevalence of cognitive impairment and/or poor coordination. When assessing pulmonary function in the elderly, the choice of tests will be depend on the circumstances, with the use of voluntary manoeuvres dependent on the condition of the patient.

[Asthma control in general practice: a cross-sectional survey of 16,580 patients]. / ER'Asthme, contrôle de l'asthme chez 16580 patients suivis en médecine générale.

INTRODUCTION: Little information is available about asthma control in patients followed by general practitioners care in France, although such control is one of the essential aims of their treatment. OBJECTIVES: The ER'Asthme survey sought to assess asthma control among patients visiting their general practitioner (GP) and to determine the factors associated with it. METHODS: This cross-sectional included patients with asthma diagnosed at least 12 months earlier, aged more than 6 years, and followed by a GP. It collected data on self-assessed health status, asthma control (assessed by a 3-level composite score based on the Canadian consensus criteria as adapted by ANAES: optimal, acceptable and unacceptable), and compliance. RESULTS: The study included 16,580 patients; 85% were older than 20 years, and 54% were male. Patients answered the question about their asthma control as follows: 53% "excellent" or "fine", 39% "not very good" and 8% "poor". GPs, however, assessed asthma control as optimal in 21% of patients, acceptable in 7% and unacceptable in 72%. Concordance between these two assessments was thus poor: Kappa coefficient 34.5% (95% CI [33.5%; 35.5%]). Only 59% of patients reported complete compliance with their maintenance treatment. Factors associated with optimal control were: use of fixed combination therapy (inhaled corticosteroid+long-acting beta-agonist) (OR: 3.7; 95%CI [3.5; 4.2]) normal BMI (OR: 2.4; 95%CI [2.0; 2.9]), non-smoker status (OR: 2.4; 95%CI [2.1; 2.8]), age<50 (OR: 2.3; 95%CI [2.1; 2.6]) and good compliance (OR: 1.6; 95%CI [1.5; 1.8]). CONCLUSION: Patients with asthma overestimate their asthma control, which often remains inadequate. Maintenance treatment with a fixed combination, BMI, smoking, age and compliance all influence the level of asthma control.

Clinical efficacy and tolerability of cefixime in the treatment of acute sinusitis.

In a noncomparative trial, 73 adults with acute sinusitis confirmed by x-ray received cefixime 400mg once daily for approximately 10 days. At the end of treatment, 60 patients (82%) were cured, 2 (2.7%) had improved and 7 (9.6%) had failed therapy; 4 patients were not evaluable. No relapses were observed at follow-up. Haemophilus influenzae, Streptococcus pneumoniae and Branhamella (Moraxella) catarrhalis were the main pretreatment pathogens, accounting for 65% of all bacterial isolates. Overall, 84% of pathogens were eradicated after treatment. Cefixime was well tolerated, moderate gastrointestinal disturbances being the most frequent adverse effects noted (3 of 4 patients with adverse effects). These results are comparable to those obtained with cefixime 400mg administered orally in 2 divided doses.

Comparative efficacy and safety of four-day cefuroxime axetil and ten-day penicillin treatment of group A beta-hemolytic streptococcal pharyngitis in children.

In a prospective randomized multicenter study, 308 children, ages 2 to 15 years, were randomized to receive either cefuroxime axetil suspension (N = 152; 20 mg/kg/day twice daily) for 4 days, penicillin suspension (N = 156; 45 mg/kg/day divided three times daily) for 10 days, of whom 97 and 103, respectively, had culture-proved group A beta-hemolytic Streptococcus infection. Two to 4 days after completion of the treatment, group A beta-hemolytic Streptococcus were eradicated from 85 of 97 (87.6%) children taking cefuroxime and from 90 of 103 (87.4%) taking penicillin; respective clinical cure rates were 94.8% and 96.1%. Clinical signs and symptoms resolved significantly more rapidly with cefuroxime (P < 0.05). At 28 to 32 days posttreatment the eradication of the primary isolate was confirmed in 94.4 and 91.9% of cefuroxime axetil and penicillin-treated patients, respectively. Drug-related adverse events (mainly gastrointestinal and cutaneous reactions) were reported in 2.1 and 2.7% of the cefuroxime- and penicillin-treated patients, respectively. Results indicated that a 4-day treatment with cefuroxime axetil was as effective and well-tolerated as the conventional 10-day treatment with penicillin in children with acute group A beta-hemolytic Streptococcus pharyngitis.

Evaluation of nasopharyngeal cultures for bacteriologic assessment of acute otitis media in children.

BACKGROUND: The recent emergence of penicillin-resistant Streptococcus pneumoniae, particularly in acute otitis media (AOM), has increased interest in the development of noninvasive procedures that might help to predict the bacterial etiology of this condition. We conducted an open multicenter study to evaluate the predictive value of the nasopharyngeal (NP) sampling in children with AOM by comparing the bacteriologic results of NP cultures with those of pus collected by myringotomy in the same patients. METHODS: The NP secretions and the pus obtained by myringotomy were collected concomitantly in 354 children younger than 6 years of age with clinical signs of AOM. The clinical usefulness of NP culture was determined by calculating its sensitivity and specificity, and especially its positive and negative predictive values for the three main pathogens responsible for AOM, Haemophilus influenzae, S. pneumoniae and Moraxella catarrhalis. RESULTS: A positive NP culture was found to have little predictive value for H. influenzae (52%), S. pneumoniae (43%) and M. catarrhalis (19%). In contrast the negative predictive value of NP cultures was much greater and was accompanied by negative middle ear fluid cultures in more than 95% of children, especially for S. pneumoniae. Furthermore the incidence of beta-lactamase-producing strains of H. influenzae at both sampling sites was similar (30 and 35%, respectively), as was the incidence of penicillin-resistant S. pneumoniae (50 and 54%). CONCLUSION: It appears that the correlation between results of NP and middle ear fluid cultures in children with AOM is too weak to allow NP culture to be recommended for the bacteriologic documentation of this disease. However, these results should not overshadow the considerable epidemiologic value of NP cultures, particularly with reference to the monitoring of pneumonococcal susceptibility in children. The collection of NP cultures should therefore be promoted for their collective epidemiologic value.

The burden of COPD in France: results from the Confronting COPD survey.

Chronic obstructive pulmonary disease (COPD) is an obstructive lung disorder characterized by progressive airflow limitation that is not reversible or only partially reversible, including chronic bronchitis and emphysema. Confronting COPD in North America and Europe was the first large-scale international survey to attempt to quantify the country-specific burden of the disease, collecting data on clinical outcomes, healthcare resource utilization, and lost productivity, from patients and physicians in France and seven other countries. The economic analysis of the French survey results showed that patients with COPD required considerable utilization of healthcare resources, with annual direct costs estimated at Euro 530 per patient In addition, COPD-related illness or disability prevented many patients from working, with an estimated annual indirect cost of Euro 1078 per patient The survey suggested underdiagnosis and undertreatment of COPD by healthcare professionals, and patients reported poor symptom control. The cost of unscheduled care (Euro 151) was almost double the cost of scheduled visits to healthcare professionals (Euro 82). This suggests that improving the long-term management of chronic symptoms by healthcare professionals could reduce the burden of disease. As in other countries, the clinical management of COPD in France may be improved by following guideline recommendations for COPD treatment. These include smoking cessation at all stages of the disease, regular treatment of chronic symptoms with bronchodilators in dyspnoeic patients, and pulmonary rehabilitation. The results of the survey also showed that the societal cost of COPD was considerably greater in patients with severe disease (Euro 2882) compared with mild COPD (Euro 289). This suggests that interventions that could help delay the progression of COPD to the advanced stages of the disease (such as smoking cessation) could be of economic benefit.

[The AIRE Study: data analysis of 753 European children with asthma]. / Etude AIRE: analyse des données recueillies chez 753 enfants asthmatiques en Europe.

PROBLEM: To analyse the paediatric data from the AIRE study (Asthma insights and reality in Europe) describing the standard of asthma control in Europe. MATERIAL AND METHODS: Among the 73,880 households contacted by telephone in 7 countries 753 children under the age of 16 were identified. An interview was conducted with a close relative to determine the frequency and severity of symptoms during the recent month, visits to casualty and hospital admissions during the past year, the medications used, the effects on the lives of the children, the opinions of the parents on the level of control of asthma and the monitoring methods used. RESULTS: 38.2% of children reported diurnal symptoms and 28% disturbance of sleep at least once a week. The consequences were important: limitation of sporting activities (29.5%) and absence from school (42.7% in the past year). Treatment was inadequate: 26% of children used inhaled steroids yet 45.9% had persistent asthma. The level of control was overestimated: 61% of parents of children with severe persistent asthma considered the asthma to be well controlled. CONCLUSION: European asthmatic children are poorly controlled, under-treated and rarely followed up. The consequences, particularly absence from school, should stimulate an improvement in their therapeutic and educational management.

[Cost of systemic lupus erythematosus for adult patients with active and treated disease in France (LUCIE study)]. / Coût du lupus systémique en France des patients adultes avec une maladie active et traitée (étude LUCIE).

PURPOSE: To evaluate in France the annual direct medical cost of adult patients with active systemic lupus erythematosus (SLE) on medication and estimate the cost of a flare. METHODS: A two-year, observational, retrospective, multicenter study, carried out between December 2010 and February 2011. Patients' characteristics, SLE disease activity and severity, rate of flares, healthcare consumption (medications, hospitalisations, etc.) were evaluated. Medical costs were assessed from the national Health Insurance perspective. Cost predictors were estimated using multivariate regression models. RESULTS: Eight centres specialized in SLE management included 93 eligible patients (including 50.5% severe). The mean age was 39.9 (11.9) years and 93.5% were women. At baseline, the mean SLE duration was 9.8 (6.6) years. The mean scores of the SELENA-SLEDAI instrument and the SLICC/ACR index were higher in severe patients (9.8 vs 5.6, and 1.2 vs 0.4 respectively; P<0.001). Over the study period, 51% of patients received the combination containing at least corticosteroids or immunosuppressants. The mean annual direct medical cost of severe patients was €4660 versus €3560 for non-severe patients (non-significant difference). The cost of medications (61.8% of the annual cost) was higher in severe patients (€3214 vs €1856; P<0.05). Immunosuppressants and biologics represented 26.5% and 4.6% of the annual total cost respectively. Patients experienced on average 1.10 (0.59) flares/year, of which 0.50 were severe flare. The occurrence of a new severe flare incremented the annual cost of €1330 (P<0.05). CONCLUSION: Medications represented the major component of the annual direct medical cost. Severe flares increase significantly the cost of SLE care management.

Patterns of systemic lupus erythematosus expression in Europe.

OBJECTIVES: To analyse the differences in disease expression of European SLE patients based on gender, age at diagnosis, and ethnicity. METHODS: A two-year, retrospective, multicentre, observational study was carried out in five countries (France, Germany, Italy, Spain and the UK). Patients' clinical manifestations including disease activity, organ involvement, organ damage and flares were analysed. RESULTS: Thirty-one centres enrolled 412 consecutive eligible patients (90.5% of women), with active disease, stratified by disease severity (half severe and half non-severe). Baseline characteristics included; mean (SD) age: 43.3 (13.6) years, SLE duration: 10.7 (8.0) years and age at disease diagnosis: 32.6 (13.0) years old. The mean (SD) SELENA-SLEDAI and SLICC/ACR scores were: 8.1 (6.7) and 0.82 (1.36), respectively. Over half of patients experienced flares (54.9%). The average number of annual flares was 1.01 (0.71) flares/year. In males compared to females, the renal system was more frequently active (53.8% vs 30.0%, p=0.002), the mean SLICC/ACR score was higher (1.15 vs 0.79, p=0.039) and the pulmonary system was more likely to be damaged (12.8% vs 3.8%, p=0.010). Furthermore, patients diagnosed at younger age displayed more renal system activity (young: 56.3% vs adult: 33.4% vs elder: 8.9%, p<0.001) and renal damage (25.0% vs 6.9% vs 2.2%, p=0.018) compared to the others. The annual number of flares (1.13 vs 1.05 vs 0.81 flares/year, p<0.0001), including the occurrence of severe flares (0.58 vs 0.51 vs 0.20, p<0.0001), was also higher in these patients. Conversely, greater organ damage was observed in patients diagnosed at an older age compared to the others. The mean SLICC/ACR score was higher (1.31 vs young: 0.88 and adult: 0.78, p<0.001) in patients diagnosed in the older age groups. The pulmonary (13.3% vs younger: 0% vs adult: 3.7%, p=0.030) and cardiovascular (17.8% vs younger: 0% vs adult: 2.9%, p<0.001) systems were more frequently damaged in these patients. Black African descents showed greater disease activity compared to Caucasian patients. They flared more often (77.1% vs 48.6%, p=0.001) and experienced a greater number of annual flares (1.57 vs 0.89 flares/year, p<0.0001), mainly more severe flares (0.89 vs 0.38/year, p<0.0001). They also were more likely to experience renal system damage. CONCLUSION: The study showed clearly two patient subsets. The disease was the most active in Black African descents, and this phenomenon has never been described before in continental Europe. The disease was also more active in patients diagnosed at a younger or adult. Greater disease damage was observed in males and in patients diagnosed at an older age.

[Phenotype of asthmatic patients according to a score derived from the Asthma Control Test]. / Phénotype des patients asthmatiques selon le score dérivé de l'Asthma Control Test.

UNLABELLED: Today the control of asthma is a key element of national and international guidelines. The ER'Asthma survey, created in 2003, measured the control of asthma and its determinants in a primary care population. The aim of the current analysis of the ER'Asthma database was to characterize the phenotype of asthmatic patients according to three levels of control by using a score derived from the Asthma Control Test (ACT). METHOD: An ancillary descriptive analysis of a cross-sectional epidemiological survey of 15,534 asthmatic patients. A score derived from the ACT was calculated for each patient by using an algorithm applied to five questions from the ER'Asthma questionnaire and similar to those of the ACT. The analysis looked for association between the patients' characteristics and the different levels of control. RESULTS: The uncontrolled patients were more likely to be obese, smokers, older, treated by a single drug, non-compliant and to have a poorer quality of life. CONCLUSION: The use of a validated three-level score has confirmed the phenotypes of poorly controlled patients. ACT not only evaluates asthma control but could also be the starting point of a discussion with the patients on the correction of modifiable risk-factors and the necessary compliance with treatment.

Clinical outcome of acute otitis media caused by pneumococci with decreased susceptibility to penicillin.

Raw data from 4 clinical studies involving pre-inclusion paracentesis were pooled to assess demographic characteristics and clinical outcome of acute otitis media (AOM) due to S. pneumoniae with decreased susceptibility to penicillin (SpRP). Children in the age range 3 months to 10 years were treated with beta-lactam antibiotics for 10 days. 54 children with SpRP AOM were compared with 182 children with penicillin-susceptible pneumococcal (SpSP) (AOM). The groups were found comparable with regard to sex, age at first AOM, and frequency of earlier bouts of AOM. SpRP AOM was significantly more frequent before age 18 months (40/54 versus 85/166 in the SpSP group; p = 0.003) and associated with more clinical failure on days 4-10 (10/54 versus 14/166; p = 0.03). These results suggest that the antibiotic treatment used to treat AOM in children under 18 months should be reconsidered in areas with a high incidence of SpRP.

Coryneform bacteria isolated from middle ear fluid.

Nineteen strains of facultatively anaerobic gram-positive rods isolated in pure culture from middle ear fluids were identified. All effusions were collected by tympanocentesis in children with acute otitis media. Identification of microorganisms to the genus level was done by studying the cell wall composition. Sixteen strains contain meso-diaminopimelic acid and arabinogalactan polymer but lack mycolic acids; therefore, these strains do not belong to a previously described taxon. Because of similarities with Corynebacterium afermentans (Centers for Disease Control group ANF-1), we temporarily classified these mycolateless strains ANF-1 like. Isolation of these microorganisms in pure culture from middle ear fluids collected by tympanocentesis is a strong argument for their involvement in acute otitis media.

[Bacterial epidemiology of acute otitis media]. / Epidémiologie bactérienne de l'otite moyenne aiguë.

Since the middle of the 1980's, Haemophilus influenzae is the most common bacterial species responsible for acute otitis media in France, followed by Streptococcus pneumoniae. Haemophilus influenzae has maintained its leading position since 1985, but the rate of pneumococcal acute otitis media is increasing fairly steadily. The other recent change with regard to the distribution of bacterial agents is the emergence, four years later than in North America, of Branhamella catarrhalis which currently accounts for 10% of cases of acute otitis media. Modifications in the behavior of microorganisms in relation to antimicrobials usually given to treat upper respiratory tract infections have occurred. Staphylococcus aureus and Branhamella catarrhalis have always exhibited marked resistance to ampicillin due to the production of beta-lactamases. Resistance of Haemophilus influenzae to ampicillin has been increasing gradually since 1985, again with a lag of a few years as compared with the United States; at present, this form of resistance is seen in approximately 35% of strains. More recently in France, 20% of pneumococcal strains recovered from middle ear pus have been shown to have abnormal susceptibility to penicillin. These changes in the behavior of the two main pathogens, i.e., Haemophilus influenzae and Streptococcus pneumoniae, require implementation of rigorous multiregional epidemiologic surveillance programs and may justify reappraisal of current therapeutic approaches.

Clonal distribution of penicillin-resistant Streptococcus pneumoniae 23F in France.

We studied the clonality of clinical isolates of Streptococcus pneumoniae 23F, the serotype most often associated with penicillin resistance in France. Clinical isolates obtained between November 1992 and April 1993 from nasopharyngeal samples from children with acute otitis media from different regions of the country were analyzed. The genetic polymorphism of penicillin-susceptible and -resistant 23F isolates (MIC, 2 mg/liter) was studied by pulsed-field gel electrophoresis. The resistant isolates were closely related, whereas the susceptible isolates were genetically heterogeneous. PCR amplification and restriction of the genes encoding penicillin-binding proteins (PBPs) 1A, 2B, and 2X also showed that the 24 resistant isolates had similar patterns which were very different from those of the susceptible isolates. All resistant isolates gave the same PBP pattern, with low affinities of PBPs for penicillin. Our results indicate that, in contrast to penicillin-susceptible 23F isolates, the penicillin-resistant 23F isolates have a single clonal origin, suggesting the rapid clonal spread of a resistant epidemic strain throughout the country.