Save antibiotics. What can be done to prevent a forecasted disaster! Suggestions to promote the development of new antibiotics.

New antibiotics are needed because of the increasing resistance of bacteria but they will be available in years to come only if drastic changes are implemented in development strategies, evaluation, use, and financing. Over the last decade, various opinions were stated and limited action was undertaken. Optimizing antibiotic use (as the "antibiotic plan" in France) was indispensable, but the process is still on going, and this is only part of the problem. Major questions are recurrently raised such as improvement of development procedures for new antibiotics, optimizing diagnostic methods, innovating financing modalities, or rescue of "old" antibiotics at risk of being withdrawn from the market. The symposium organized in September 2009 by the Swedish EU presidency helped to support previous recommendations. But conclusions remain unspecific. The propositions which are made here, after a work session, have for aim to be more detailed and innovating, even if they can be discussed, or even provocative.

[Current epidemiology of microbial low respiratory tract infections]. / Epidémiologie microbienne des infections respiratoires basses actualités.

The recent literature brings nothing new since it provides only fragmented, though undoubtedly useful, studies which remain within the prevalence interval for the different bacterias. The occurrence of germs varies with time and space; nevertheless, whatever the studied series and the site of the studies, the 3 most frequent causal germs belong to the following five strains: Streptococcus pneumoniae, Influenza A, Mycoplasma pneumoniae, Haemophilus influenzae, and Legionella pneumophila. Thus, 90% of all documented pneumoniae appear to be caused by the following pathogens: Pneumococcus; most frequent in hospitalized patients; Mycoplasma, Chlamydia and respiratory viruses were predominant in outpatients, with great variations; Staphylococcus and enterobacteriace may be encountered, mostly in elderlies with major debilitating diseases; association of germs, generally including pneumococcus, are increasingly identified. Last, in 25% to 50% of cases, the causal agent is not known. Recently, some Staphylococcus meticillin-resistant were identified. The diagnosis of viruses (as well as that of atypical bacterias) seems to have improved, thanks to the use of PCR though the interest of such a diagnosis remains questionable, except for epidemiological studies, as well as the relevance of this type of test in clinical practice. Nothing really new has come out on the epidemiology of acute bronchitis, while in bacterial exacerbation of COPD, attention focused on the colonizing or infective role of H. influenzae in the genesis of bronchus inflammation.

Oral contraception and unprotected sex with occasional partners of women HIV-infected through injection drug use.

Among HIV-infected women, unprotected sex with the main sexual partner is common practice. Conversely, studies about condom use with sexual partners of unknown HIV sero-status are sparsely reported. We aimed to assess the impact of oral contraception on unsafe sexual behaviours with occasional partners in women HIV-infected through injection drug use. The analysis focused on 90 women, enrolled in the French cohort MANIF 2000 and reported having engaged in sexual relationships with occasional partners during a 48-month period. Visits where women reported unprotected sex with occasional partners in the prior 6 months were compared to visits where they reported protected sex using a logistic model based on Generalised Estimating Equations. Unprotected sex with occasional partners was independently associated with oral contraception (OR[95%CI] = 3.2[1.4-7.2]), reporting only one occasional partner (OR[95%CI] = 3.1[1.6-6.2]) and antiretroviral treatment receipt. No significant association was found between unprotected sex and CD4 level or plasma viral load. With the growing population of people living with HIV as a chronic infection, the development and evaluation of HIV-prevention interventions tailored toward women remain a public health priority. Risk reduction counselling and interventions are needed to promote either the use of dual contraception or, alternatively, that of female condom.

Nécessité d'approches alternatives dans les stratégies d'évaluation des nouveaux antibiotiques antibactériens.

The golden age of antibacterial antibiotics extend from year 1941 to the 1990s decade. At that time, something like an earth quake occurred: from the thirty molecules or so whose development was being achieved or was already marketed, only three were put on the French market, and faced the greatest difficulties to be prescribed by practicians, because: However, while the debate is raging, many of us think "yes we do", as it is a duty to anticipate today the consequences of tomorrow's bacterial resistances. This paper presents three types of propositions to optimise the development of future molecules: The development of new concepts to develop new drugs which would be active against tomorrow's bacteria compels us to manage in a new fashion today's systems, which have reached their own limits.

[Efficacy and safety of telithromycin in the treatment of acute exacerbation of chronic obstructive pulmonary disease]. / Efficacité et tolérance de la télithromycine dans le traitement de l'exacerbation aiguë de bronchite chronique obstructive.

UNLABELLED: The aim of this study was to evaluate the clinical efficacy of telithromycin administered for 5 days at a dosage of 800 mg/day, in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) presenting with at least 2 of Anthonisen's criteria including the increase of purulence. METHODOLOGY: During this multicenter (211 private lung specialists), prospective, non-comparative, open-labeled French study, 365 patients were included between April 2002 and March 2003. Clinical efficacy was assessed on D12-D19 by the rate of clinical success as defined by recovery or clinical improvement (main endpoint) according to the number of exacerbation episodes during the previous year. RESULTS: On D12-D19 clinical success rate in the per protocol global population was 88.0% and respectively 87.9% in patients with or=4 episodes in the previous year. These success rates were similar to those in the intent-to-treat population. Safety, assessed on 359 patients, was satisfactory, with mainly digestive disorders related to the treatment in 3.9% of the patients. No treatment-related serious adverse events were observed. CONCLUSION: This study, conducted among private practitioners in France according to COPD classification as defined by official recommendations, validates the results obtained in previous studies. Our results confirm the place attributed to telithromycin in the treatment of patients presenting with AECOPD without chronic respiratory failure, according to ongoing official recommendations.

[Need for alternative approaches in the evaluation of new antibacterial antibiotics]. / Nécessité d'approches alternatives dans les stratégies d'evaluation des nouveaux antibiotiques antibactériens.

The golden age of antibacterial antibiotics extend from year 1941 to the 1990s decade. At that time, something like an earth quake occurred: from the thirty molecules or so whose development was being achieved or was already marketed, only three were put on the French market, and faced the greatest difficulties to be prescribed by practicians, because: the knights of good practice want a strict limitation of their use to precise indications; the pharmaceutical companies find that the return on investment is almost impossible; the prescribers are stunned by the inconsistency between the MAs, the advances in science and the health economic authorities advices which claim that these products are not very interesting; the research for new antibiotics is stalling; thus, for the first time in 60 years, an iconoclastic question arises: do we need new antibiotics? However, while the debate is raging, many of us think "yes we do", as it is a duty to anticipate today the consequences of tomorrow's bacterial resistances. This paper presents three types of propositions to optimise the development of future molecules: sharpening of the data concerning preclinical security for a better predicting of both the activity and the toxicity; improvement in performances and organization of clinical trials, which implicates to reconsider some of the present methodological rules; inclusion in the evaluation data of some relevant and new features measuring the anti-bacterial activity while taking into account the present and future bacterial resistances. The development of new concepts to develop new drugs which would be active against tomorrow's bacteria compels us to manage in a new fashion today's systems, which have reached their own limits.

[Efficacy and safety of pristinamycin vs amoxicillin in community acquired pneumonia in adults]. / Essai comparatif de l'efficacité et de la tolérance de la pristinamycine vs amoxicilline dans le traitement des pneumonies aiguës communautaires de l'adulte.

STUDY OBJECTIVE: Evaluation of efficacy and safety of pristinamycin (PRI), compared with amoxicillin (AMX), both at 3 g daily for 7 to 10 days in adults with community-acquired pneumonia (CAP). PATIENTS AND METHODS: Multinational, randomized, double blind, double dummy clinical trial of non-inferiority was conducted in 399 patients with a CAP. RESULTS: At inclusion, the mean age was 47.8+/-18.3 years, 24.3% patients were 65 or older. The Fine score was < or =III in 85.4% patients. The bacterial etiology was documented in 34.8% of patients: Streptococcus pneumoniae (48.1%), Mycoplasma pneumoniae (18.6%), Haemophilus influenzae (14.7%), Chlamydia pneumoniae (13.2%), Legionella pneumophila (9.3%). In the clinical per-protocol population, the clinical success rate was 87.6% in each group: 149/170 patients (PRI) and 148/169 (AMX); The 95% confidence interval was [-6.61%; 7.23%]. In modified intend to treat population, the clinical success rate was 79.9% (151/189) in the PRI group and 83.0% (151/182) in the AMX group [CI 95% (-10.87%; 4.69%)]. A satisfactory bacteriological response was observed in 82.3% (51/62) of PRI patients and 88.1% (59/67) of AMX patients. Treatment related adverse events occurred similarly in both groups according to the expected tolerance profile of the two drugs. No serious adverse events in both groups were related to the study drugs. CONCLUSIONS: In this study, PRI 3 g daily was clinically as effective and well tolerated as AMX 3 g daily, for 7 to 10 days, in PPc, in the treatment of bacterial community-acquired pneumonia.

[Epidemiology and diagnosis of respiratory syncitial virus in adults]. / Epidémiologie et diagnostic des infections à virus respiratoire syncytial de l'adulte.

INTRODUCTION: Respiratory syncytial virus (RSV) is rarely searched for in respiratory infections in adults. This study assessed its frequency and diagnosis. METHODS: Three separate studies were conducted in adults presenting with (1) a flu-like illness, (2) a lower respiratory tract infection in the community, and (3) a severe pneumonia requiring hospitalisation. The diagnosis of RSV infection was sought by PCR in all cases, and compared to antigen detection and culture in two studies. RESULTS: RSV was identified in 20 (11.7%) of 170 influenza-vaccinated adults suffering from flu-like symptoms. In the 270 cases of non-severe lower respiratory tract illnesses in the community, viruses were identified in 86 (31.8%) cases, with RSV accounting for 13 (4.8%). In the 164 cases of acute bronchitis, a virus was detected in 64 (36.7%) of which 11 (6.3%) were RSV, 37 (21.3%) rhinovirus, 5 influenza viruses A and B, and 12 other viruses. In the 60 cases of infective exacerbations of chronic bronchitis, rhinovirus was detected in 9 (15%) and para-influenza 3 virus in 2 cases. In the 21 acute pneumonia's, 1 RSV, 1 influenza virus A and 2 rhinovirus cases were detected as well as 1 RSV, 1 parainfluenza 3 viruses and 4 rhinovirus cases in the 11 lower respiratory tract illnesses in patients with pre-existing lung disease. There were overall 19 viral and bacterial associated infections. Finally, in the 51 acute pneumonias hospitalised with respiratory distress syndrome, a virus was identified in 17 (33.3%) cases, including 3 (5.5%) RSV, 6 influenza A, 3 rhinovirus, 2 adenovirus, 2 herpes simplex virus and 1 cytomegalovirus. There were 6 bacterial-associated infections, and 4 were hospital-acquired. All RSV-infected patients were old people and had chronic pulmonary or cardiac disease. CONCLUSIONS: In adults, RSV is a frequent cause of flu-like symptoms. It can sometimes cause lower respiratory tract illness, which can be severe, and should be considered in the differential diagnosis in such cases. The PCR method is a particularly effective diagnostic test, but as yet is not routinely available.

Hospitalization for depressive syndrome in a cohort of HIV-infected patients contaminated through injecting drug use: MANIF 2000 cohort, France, 1995-1999.

The objective of this study was to estimate the relative impact of hospitalization for depressive syndrome (DS) on all causes of hospitalization and characterize individuals more likely to experience hospitalization for DS in the French cohort study, Manif 2000, of patients HIV infected through injection drug use. We selected all patients followed-up to the 24-month visit (C24) who missed no more than one visit. Using medical records, dates and causes of hospitalizations, were collected retrospectively. A Poisson regression model based on generalized estimating equations was used to identify factors associated with hospitalization for DS. During the study period, 223 hospitalizations were recorded for 120 of the 335 selected patients. DS was the second reason for hospitalization after infections, accounting for 14.3% of the total number of hospitalizations. DS was reported in 32 hospitalizations and involved 24 patients, five of them being hospitalized more than once for the same cause. Factors independently associated with hospitalization for DS were history of multiple incarceration (RR = 2.1, 95% CI: 1.0-4.7), polydrug use (RR = 2.6, 95% CI: 1.1 -5.9) and lack of stable relationship (RR = 4.2, 95% CI: 1.6- 11. 1). In the HAART era, DS represents an important cause of hospitalization of HIV-infected injecting drug users, mainly concerning patients presenting no stable relationship and signs of social instability. Scheduled psychiatric consultations for these patients would permit us to identify those for whom major depression might lead to hospitalization and provide them with timely and appropriate care.