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Infections à pneumocoque
Abstract
Currently, pneumococcal infections are a public health problem. Streptococcus pneumoniae is a leading cause of community acquired invasive and non invasive bacterial infections in infants and young children, more specifically among those under five years. Pneumococcal invasive infections, in particular meningitis, carry a mortality upper than 8 % and a high risk of sequelae. Atypical clinical expression is frequent in youngest children. Membrane immunochromatography for rapid detection of urinary C-polysaccharide antigen is one of the advances for biological diagnosis, but it remains to be evaluated in children. Due to the increasing prevalence of penicillin-resistant pneumococci, treatment has to be adapted to clinical and epidemiological features. Frequent, serious, antibiotic-resistant characters of pneumococcal infections plea for vaccine. In France, Pneumo 23® indications were extended in 1998, and pneumococcal conjugate vaccine Prevenar® indications were modified in 2002. Local, national and international surveys are needed to adapt treatment and vaccine strategies.
... Le rôle de la capsule dans les processus physiopathologiques est très important et sera décrit au chapitre II.1. (Brisou 2004). Malgré la diversité capsulaire, tous les gènes impliqués dans la synthèse sont organisés de façon similaire dans un locus génétique cps localisé entre les deux gènes dexB et AliA. ...
... Le pneumocoque est sensible à la plupart des antibiotiques actifs sur les bactéries Grampositif, à savoir les β-lactamines (pénicilline, céphalosporine, amoxicilline, etc...), les macrolides, les tétracyclines, le chloramphénicol, la rifampicine, le cotrimoxazole et les glycopeptides (Brisou 2004). Chacun de ces antibiotiques cible un processus essentiel au développement ou à la survie de la bactérie. ...
... Le choix du traitement antibiotique dépend essentiellement de la pathologie considérée et des recommandations des autorités nationales de santé. Dans les cas de pneumopathies et d'otites moyennes aiguës à pneumocoque, c'est la prescription d'amoxicilline en monothérapie qui est privilégiée ; dans le cas de méningites, l'association de deux antibiotiques ciblant la paroi est préconisée : le céfotaxime associé à la vancomycine ou à l'amoxicilline (Brisou 2004). ...
... La pneumonie est une atteinte infectieuse des poumons causée par plusieurs germes pathogènes. Sa mortalité est la sixième cause de décès et la première cause de décès par pathologies infectieuses [1]. Les formes sévères de pneumonie sont principalement dues à Streptococcus pneumoniae [1]. ...
... Sa mortalité est la sixième cause de décès et la première cause de décès par pathologies infectieuses [1]. Les formes sévères de pneumonie sont principalement dues à Streptococcus pneumoniae [1]. Streptococcus pneumoniae est une espèce naturellement sensible à la plupart des antibiotiques actifs sur les bactéries à Gram positif [2], mais l'acquisition de résistances vis-à-vis de ces familles d'antibiotiques représente un problème de santé publique. ...
RESUME : Une des méthodes communément utilisée en pharmacochimie est le docking moléculaire, elle consiste à prédire et reproduire les interactions protéine ligand. FlexX est parmi les programmes de docking moléculaire les plus utilisés. Nos résultats montrent qu'il est assez performant pour reproduire les tests expérimentaux puisque 79.24 % des valeurs de RMSD calculées sont inférieures ou égale à 2Å. Il a été utilisé pour étudier l'inhibition du peptide déformylase de Streptococcus pneumoniae. Cette étude a fait ressortir le VRC 4307 comme meilleur inhibiteur. L'étude de la modélisation réalisée sur cet inhibiteur montre que le remplacement du radical méthyle en position 4 du noyau thiazole par un groupement carbonyle et la partie hydrophobe P1' par d'autres groupes de même nature diminue l'énergie d'interaction de 15 unités. L'étude des propriétés pharmacocinétiques de ce composé proposé montre qu'il s'inscrit parfaitement dans la marge des critères imposés par la règle de Lipinski. Mots clés : Docking moléculaire, les interactions protéine ligand, FlexX, peptide déformylase, antipneumocoques, règle de Lipinski. ABSTRACT: One of the methods commonly used in pharmacochemistry is the molecular docking, it consists in predicting and in reproducing the protein ligand interactions. FlexX is one of the most used molecular docking programs. Our results show that it is rather successful to reproduce the experimental tests because 79.24 % of the values of RMSD are lower than 2 Å. It was used to study the inhibition of a peptide déformylase belonging to Streptococcus pneumoniae. This study highlighted the VRC 4307 as the better inhibitor of the enzyme. The study of the modelling realized on this inhibitor show that the replacement of the methyl group in position 9 of thiazole ring by a carbonyl and the hydrophobic part P1', by other groups of the same nature decreases the energy of interaction of 15 units. The study of the pharmacokinetic properties of these proposed molecules shows that they join perfectly the margin of the criteria imposed by the rule of Lipinski.
... L'objectif de ce travail est de mettre le point sur le portage rhinopharyngé du S. pneumoniae, la prévalence, les facteurs de risque de ce dernier, ainsi que les sérotypes circulants en portage chez les enfants âgés de moins de deux ans. Brisou et al., 2010). S. pneumoniae colonise fréquemment les voies respiratoires de l'Homme. ...
... Chez l'adulte, lors d'infection invasive ou de pneumonie, plusieurs études ont montré l'intérêt de ce test pour établir un diagnostic rapide et précoce, même après plusieurs jours d'antibiothérapie (Dominguez et al., 2001; Pesola, 2001; Smith et al., 2003). Enfin, dans les cas difficiles, il est possible d'avoir recours à des techniques de biologie moléculaire comme la polymerase chain reaction (PCR) qui permettent une détection rapide des pneumocoques et de leurs résistance (Brisou et al., 2010). tous les enfants en sont porteurs à un moment ou à un autre de l'année. ...
... Ce phénomène peut être expliqué par une difficulté de diagnostic de la coqueluche chez l'adulte et une couverture vaccinale insuffisante. (12). ...
L’hésitation vaccinale désigne un terme récemment défini par l’OMS pour caractériser les comportements négatifs envers la vaccination. C’est un phénomène particulièrement important en France et dans les pays industrialisés qui augmente insidieusement depuis quelques années. Ce manque d’adhésion est en partie responsable du niveau insatisfaisant de certaines couvertures vaccinales. La diminution de ces couvertures provoque la résurgence de maladies et le déclenchement d’épidémies. Le doute vaccinal est donc un enjeu de santé publique et un sujet important à étudier pour les professionnels de santé. Cette synthèse bibliographique s’attache donc à définir cette hésitation vaccinale grâce à l’étude des modèles qui l’illustrent et des facteurs qui la composent. Ces facteurs représentent les principaux arguments utilisés par les mouvements anti-vaccins. Ils peuvent être classés en fonction de leur cible en facteurs contextuels, individuels ou propres à la vaccination. La compréhension des déterminants qui influencent l’hésitation vaccinale permet la construction de stratégies permettant de lutter contre cette dernière dont certaines seront exposées dans cette thèse. Enfin, ce travail a également pour vocation de présenter des clés aux professionnels de santé afin de plus facilement défendre la vaccination et d’apaiser les peurs de leurs patients.
... Globally, resistance to beta-lactams reached 55.4% in France in 2001 [5] and 53.3% in Spain in 2004 [6]. Resistance to the beta-lactams comprises more than 50% of cases of resistance to one or many antibiotics families [7]. ...
Monitoring of Streptococcus pneumoniae antibiotic resistance is of great importance due to the frequency of strains becoming increasingly resistant to antibiotics. In this study, we report the antibiotic susceptibility of the serotypes of S. pneumoniae strains isolated from healthy children aged 1-24 months in the Marrakech region of Morocco. Resistance to penicillin (38.7%) was frequently associated with resistance to other antibiotics. The highest rates of resistance were to cotrimoxazole (trimethoprim/sulfamethoxazole) (49.3%), erythromycin (48.7%), tetracycline (37.3%), lincomycin (35.3%), chloramphenicol (32.7%) and ciprofloxacin (24%). Prisitinamycin and vancomycin were effective against all isolated pneumococcal strains (100% sensitive strains). Gentamycin demonstrated good efficacy on S. pneumoniae, with 98.7% of strains being sensitive. Multidrug resistance characterized 43.33% of all studied strains. Of the multidrug-resistant strains, 36.92% were resistant to erythromycin (E), tetracycline (T) and cotrimoxazole (Co: sulfamethoxazole-trimethoprim) (phenotype ETCo, n=24), and 20% had decreased susceptibility to beta-lactams, erythromycin and cotrimoxazole (phenotype PECo, n=13). A total of 29.23% of S. pneumoniae strains exhibited combined resistance to four antibiotics (phenotype PETCo, n=19). This study reports the status of resistance and multiresistance of S. pneumoniae strains in the Marrakech region of Morocco.
Objectives:
We aimed to describe the clinical, epidemiological, and outcome characteristics of IPD case patients hospitalized at the Albert-Royer National Children's Hospital (French acronym CHNEAR) to evaluate the disease burden of IPDs in a pediatric hospital of Dakar (Senegal).
Patients and methods:
All children aged 0-15 years hospitalized at the CHNEAR between January 1st, 2008 and December 31st, 2013 for a documented IPD were included in the study. Medical history, risk factors, clinical, bacteriological, and outcome data was collected. Data was then analyzed using the SPSS software, version 16 (Pearson's Chi(2) test: a P-value<0.05 was considered statistically significant).
Results:
A total of 218 IPD patients were hospitalized at the CHNEAR during the study period (hospital prevalence: 0.79%). The mean age was 36.1 months. The male to female ratio was 1.27 (122 boys and 96 girls). Infants<2 years of age represented 61.46% of patients. Prior antibiotic therapy was found in 54% of patients but details were lacking. Infection sites were mostly meningeal (61%) and pleuropulmonary (28.9%). The main isolated serotypes were 1, 6A, 14, 5, and 23F. Case fatality was 17.4% and it was five times higher for pneumococcal meningitis.
Conclusion:
IPDs are very common in children in Senegal. Infants<2 years of age are particularly affected. The very high case fatality (17%) was significantly associated with meningeal infection sites hence the need for better access to pneumococcal vaccines.
Streptococcus pneumoniae is a major human pathogen, which causes pneumonia, meningitis and septicemia. To insure its survival and dissemination, the pneumococcus deploys an array of virulence factors promoting invasion of tissues and evasion from the immune system. A particular class of proteins not associated with any known export system, the moonlighting proteins, is found at the pneumococcal surface. Moonlighting proteins are conserved cytoplasmic metabolic enzymes or molecular chaperones localized in various cellular compartments and exhibiting additional functions. The glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is found at the surface of numerous eukaryotic and prokaryotic cells, and display diverse roles in the virulence processes of pathogenic organisms.
The pneumococcal surface GAPDH acts as a virulence factor by binding to host plasminogen/plasmin, which facilitates the bacterial invasion through the extracellular matrix and the endothelial and epithelial cell barriers. However, the mechanisms leading to the GAPDH export and binding to the bacterial surface had not been deciphered yet. This work demonstrates that the GAPDH is released upon cell lysis and associates with the peptidoglycan.
C1q, a key component of the classical complement pathway, is a major player in the response to microbial infection and has been shown to detect noxious altered-self substances such as apoptotic cells. The use of complementary experimental approaches allowed the identification of the GAPDH as a C1q partner when exposed at the surface of S. pneumoniae and human apoptotic cells. However, and rather unexpectedly, the pneumococcal GAPDH activates the complement cascade unlike the human one. Those results encourage further studies in order to understand how C1q recognition of two closely related proteins can lead to such striking differences on its complement activation properties.
Pneumococcal infections are a major public health problem because of the virulence of this bacterium and its ability to develop resistance.
Two hundred and ninety-four strains of Streptococcus pneumoniae were isolated from sterile (56.8%) and non-sterile samples (43.2%), from January 2001 to July 2010.
The interpretation of antibiotic susceptibility testing, according to CLSI criteria (M100-S21 2011), yielded a 25.2% overall resistance to penicillin, with 23.5% of strains isolated from CSF (meningitis), and only 1.7% in other samples. Resistance to cefotaxime was 8.1% (including 4.4% at a high level). The most common serotypes were: 14 (19.5%), 23F (9.7%), 6B (9.3%), 19F (5.4%), and serotype 1 (5%). The percentage of these serotypes isolated from normally sterile sites in children under 5 years of age was 31.25% for 14, 10.4% for 23F, 8.3% for 19F, 6.25% for 6B, and 4.2% for serotype 1. The theoretical vaccinal coverage against invasive infections in children under 2 years of age was 61.5%, 69.2%, and 76.9% for the 7-valent, 10-valent, and 13-valent conjugate vaccines, respectively. Penicillin non-susceptible Streptococcus pneumoniae (PNSP) strains accounted for 67.1, 68.6, and 72.8% for each of these three vaccines.
There was a variation of serotype rates compared to previous studies. The increase in pneumococcal antibiotic resistance is concerning, particularly for the treatment of pneumococcal infections in children and infants. Pneumococcal vaccination is not compulsory yet in Algeria.
Although pneumococcal conjugate vaccines are close to being licensed, a more profound knowledge of the virulence factors responsible for the morbidity and mortality caused by Streptococcus pneumoniae is necessary. This review deals with the major structures of pneumococci involved in the pathogenesis of pneumococcal disease and their interference with the defense mechanisms of the host. It is well known that protection against S. pneumoniae is the result of phagocytosis of invading pathogens. For this process, complement and anticapsular polysaccharide antibodies are required. Besides, relatively recent experimental data suggest that protection is also mediated by the removal of disintegrating pneumococci and their degradation products (cell wall, pneumolysin). These structures seem to be major contributors to illness and death caused by pneumococci. An effective conjugate vaccine should therefore preferably include the capsular polysaccharide and at least one of these inflammatory factors.
Streptococcus pneumoniae infections are a leading cause of respiratory illness in young children, the elderly, and persons with chronic medical conditions. The emergence of multidrug-resistant pneumococci has compromised the effectiveness of antibiotic therapy for pneumococcal infections. As antibiotic-resistant strains increase in prevalence, there is a need for interventions that minimize the spread of resistant pneumococci. In this review we provide a framework for understanding the spread of pneumococcal resistance and evaluate proposed interventions to reduce this spread. Pneumococci differ from many drug-resistant pathogens because asymptomatic carriers play a key role in transmission of resistant strains and the genes encoding resistance are spread primarily by transformation and conjugative transposons. Evidence suggests that modifications of treatment regimens that have proved effective at limiting resistance in other pathogens may not prevent the spread of pneumococcal resistance. In contrast, programs encouraging more judicious antibiotic use have been shown to be effective. Additionally, a newly developed conjugate pneumococcal vaccine holds great potential as an “antiresistance vaccine” that simultaneously reduces the burden of invasive disease and the prevalence of resistant strains. Several areas of future epidemiologic and laboratory research hold promise to contribute to the reduced spread of pneumococcal resistance.
Bacterial meningitis remains a disease with associated unacceptable morbidity and mortality rates despite the availability of effective bactericidal antimicrobial therapy. Through the use of experimental animal models of infection, a great deal of information has been gleaned concerning the pathogenic and pathophysiologic mechanisms operable in bacterial meningitis. Most cases of bacterial meningitis begin with host acquisition of a new organism by nasopharyngeal colonization followed by systemic invasion and development of a high-grade bacteremia. Bacterial encapsulation contributes to this bacteremia by inhibiting neutrophil phagocytosis and resisting classic complement-mediated bactericidal activity. Central nervous system invasion then occurs, although the exact site of bacterial traversal into the central nervous system is unknown. By production and/or release of virulence factors into and stimulation of formation of inflammatory cytokines within the central nervous system, meningeal pathogens increase permeability of the blood-brain barrier, thus allowing protein and neutrophils to move into the subarachnoid space. There is then an intense subarachnoid space inflammatory response, which leads to many of the pathophysiologic consequences of bacterial meningitis, including cerebral edema and increased intracranial pressure. Attenuation of this inflammatory response with adjunctive dexamethasone therapy is associated with reduced concentrations of tumor necrosis factor in the cerebrospinal fluid, with diminished cerebrospinal fluid leukocytosis, and perhaps with improvement of morbidity, as demonstrated in recent clinical trials. Further information on the pathogenesis and pathophysiology of bacterial meningitis should lead to the development of more innovative treatment and/or preventive strategies for this disorder.
Invasive disease caused by Streptococcus pneumoniae continues to result in high morbidity and mortality throughout the world, despite the availability of antimicrobial therapy and a polyvalent pneumococcal polysaccharide vaccine. For many years the virulence of S. pneumoniae has largely been attributed to its antiphagocytic polysaccharide capsule. Recent evidence, however, indicates that pneumococcal proteins and components of the cell wall play an important part in the pathogenesis of disease, either as mediators of inflammation or by directly attacking host tissues. Some of these may be appropriate targets for improved preventative strategies against the pneumococcus.
The classification of the streptococci has changed considerably in recent years, with the description of several new species, the re-naming of others, and the re-allocation of some former Streptococcus species to different genera. Phenotypic identification schemes have not kept pace with these taxonomic developments and there is considerable scope for improvement, perhaps with increased use of rapid enzyme-based methods involving fluorogenic or chromogenic substrates. Nucleic acid probes have been described for identification of several streptococcal species and the design of such probes has been greatly facilitated by the availability of 16S rRNA sequence data for most species.
The pathogenic significance of some of the more recently described species is not fully understood. Many, if not all, of the oral streptococci appear to be involved in infective endocarditis, although not with equal frequency; several can also be a significant cause of infection in immunologically-compromised patients. Within the oral streptococci the 'Streptococcus milleri group' are frequently isolated from purulent infections and there is evidence for some specificity in the distribution of Streptococcus intermedius, S. constellatus and S. anginosus at different body sites. The S. mutans group are important aetiological agents in dental caries, and almost any of the oral streptococci may be involved in other infections in the mouth. In addition to the obvious need for more epidemiological data on the role of the newly described species in human and animal disease, further studies on their virulence mechanisms are also indicated.
(C) Williams & Wilkins 1994. All Rights Reserved.
(C) Williams & Wilkins 1997. All Rights Reserved.
Objective.
—To study the epidemiology of childhood pneumococcal invasive infections in Israel as a background for immunization programs.Design.
—A 2-year (October 1988 through September 1990) prospective, nationwide surveillance of all invasive pediatric pneumococcal infections.Setting.
—All 25 medical centers hospitalizing children in Israel, including all laboratories performing blood cultures from pediatric patients.Patients.
—Infants and children aged 0 to 12 years visiting the pediatric emergency department or hospitalized in pediatric departments were included if Streptococcus pneumoniae was isolated from blood or cerebrospinal fluid.Results.
—Four hundred sixty-nine invasive infections were diagnosed. Pneumonia, bacteremia without apparent focus, meningitis, and cellulitis were found in 39%, 37%, 17%, and 3%, respectively. The annual incidence was 42 per 100000 for children younger than 5 years of age (104 per 100000 for those <12 months old). The two most common serotypes were 1 and 5, which are rare in Western Europe and North America. Eight groups comprised 82% of all invasive infections. Extrapolated to a population in which 100 000 live births occur yearly, the total annual hospitalizations for pneumococci infections was calculated to be 1928 days. The overall case-fatality rate was 2.2%, but it was 30% during the first month of life.Conclusions.
—Pneumococcal invasive infections are common in children in Israel and carry considerable morbidity.(JAMA. 1992;268:3328-3332)
Community-acquired pneumonia remains associated with a high mortality and its management is still difficult. Numerous studies have identified short term lethal risk factors in case of CAP. Recommendations regarding the decision for hospitalization are based on associated comorbidities, short-term mortality; physicians try to sort according to risk on the basis of demographic variables (age, sex, living in a nursing home), comorbidity, physical examination, laboratory and/or radiographic findings. Clinical predictive rules that quantifies short-term mortality for patients with this illness have been proposed. Used as guidelines, these rules may help physicians make decisions on hospitalization and on the anti infectious treatment for patients with this illness
Streptococcus pneumoniae is carried nasopharyngeally by 20 %–40 % of healthy children. But this rate of carriage is highly variable. Several risk factors have been associated with Streptococcus pneumoniae carriage, including day care center attendance, the size of the day care center, living in close contact as siblings, and socioeconomic factors. The antimicrobial treatment increases the percentage of penicillin-resistant Streptococcus pneumoniae. We report a prospective study on nasopharyngeal carriage of Streptococcus pneumoniae performed during a 1-year period in children living in an orphanage representing an extreme version of the situation of a day care center; 71 children (
Morbidity and mortality in meningitis remains high in paediatric patients. Streptococcus pneumoniae is actually the first most likely organism to cause meningitis in children 2 months to 2 years old. Data from 1997 show that the rate of penicillin resistance was 53 % in paediatric patients. The increasing prevalence of antibiotic-resistant S. pneumoniae warrants the combination of cefotaxime or ceftriaxone (third generation cephalosporin) plus vancomycin as first-line therapy of presumed pneumococcal meningitis. This regimen should be continued, if the third generation MIC is ≥ 0.5 mg/L. If MIC of cefotaxime or ceftriaxone is < 0.5 mg/L, the third generation can be used alone.
Les auteurs rappellent les caractéristiques épidémiologiques, cliniques et évolutives des otites d'évolution prolongée, c'est-à-dire d'une otite présentant toujours des signes d'infection au-delà de trois semaines d'évolution. Le pneumocoque de sensibilité diminuée à la pénicilline était le principal germe retrouvé sur une série de 79 prélèvements pour otites traînantes suivies à l'Hôpital Trousseau. Les facteurs de risque sont détaillés et nous proposons une conduite à tenir thérapeutique adaptée aux circonstances cliniques.
An epidemiological study was performed in order to assess the importance of penicillin resistant pneumococci in meningitis. 75 patients were assessed, in 24 different French centers. Strains with MIC above 0.1 mg/l represented 20.4 % of the total (a total of 49 strains was studied). The total death rate reached 12 %. Only one death was reported in the group of patients infected with resistant or intermediate strains. This death was not related to therapeutic failure. This bad prognosis was related to the initial neurological status, and independant from the MIC of infecting strains, if the initial therapy used high dosages.
La survenue d'une méningite suppose que l'agent pathogène soit capable d'envahir l'espace sousarachnoidien et d'y produire une inflammation. Ceci suppose que les bactéries responsables de méningite soient capables de franchir de façon sélective la barrière hémato-méningée. Les mécanismes en cause dans ce processus sont méconnus. Cependant deux éléments semblent acquis : les bactéries méningitogènes doivent être capables d'induire des bactériémies intenses et prolongées. Une interaction étroite aux cellules endothéliales des capillaires neuro-méningés est indispensable. Les éléments ultérieurs qui font suite à l'effraction des bactéries dans le LCR et qui sont responsables de la survenue d'une inflammation sont mieux connus et en rapport avec une production locale de cytokines (TNF, et IL1 surtout). Cette production de cytokines est secondairement responsable de l'activation de l'endothélium qui est nécessaire à la margination et la diapédèse leucocytaire.
Common bacteria may be observed and cultured from the CSF. Recent technological breakthroughs have improved the detection of microbial products by physicochemical reactions, polymerase chain reaction, and antigenic techniques (specific indicators) or non specific reactions. The diagnosis use and the limits of these techniques are reviewed.
The role of capsular pneumococcal type antibodies has been well established before the antibiotics era in their capacity to protect the immune host against pneumococcal infection. Such antibodies occur during the infection, the colonization or after vaccination. These antibodies have been shown to be protective in experimental models and in human. They are acting by promoting the opsonization of encapsulated pneumococci facilitating their ingestion and killing by phagocytic cells (polymorphonuclear leukocytes and macrophages) through the activation of the complement classical pathway. Released C3a and C5a fragments are associated with recruitment of blood derived phagocytic cells in the infectious foci. The anticapsular polysaccharides antibodies involved by far are IgM and IgG2 (in adults) and IgG1 (in infants). The magnitude of the humoral response depends of the chemical composition of the capsular polysaccharide serotype, the age of the individuals, and the presence of immune complexes. According to the fact that polysaccharides are poor immunogens in infants younger than 2 years of age, their conjugaison with carrier protein will permit the opportunity to construct more efficient vaccines being able to induce memory T cells. A part of the type specific anti-capsular antibodies, several others antibodies have been detected showing specificity against several cell wall or cytoplasmic membrane associated structures (teichoic acid, polysaccharide C, Forssman antigen, pneumococcal surface protein A, pneumolysine, neuraminidase). However such antibodies may not be associated with the acquired resistance to infection, even if these bacterial molecules are constitutive of the pathophysiology of the pneumococcal infection. The review details with the recent data analysis involving the various factors responsible of the bacterial colonization, the inflammatory process and the invasivness of particular serotypes.
L'étude sur 12 ans est réalisée à Barcelone, montre que le taux de résistance des pneumocoques à la pénicilline atteint actuellement 40 %; croissance égale observée au niveau des pneumonies à pneumocoques nosocomiales et des pneumonies extrahospitalières. Le principal facteur de risque retenu face à ce phénomène est l'utilisation antérieure de β-lactamines. Dans ce cas de pneumonies graves, la ceftriaxone garde une efficacité sur des souches à résistance élevée. Cette croissance constante de la résistance du pneumocoque aux antibiotiques rend les études contrôlées indispensables pour un avenir thérapeutique optimal.
L'évolution de la résistance aux antibiotiques du pneumocoque ces dernières années, dans le monde, est inquiétante. C'est en pédiatrie, particulièrement chez les enfants qui présentent une otite moyenne aiguë (OMA) que les plus forts pourcentages de résistances sont observés. S. pneumoniae est la première bactérie de l'OMA qui est la plus fréquente des infections pneumococciques de l'enfant. Une surveillance épidémiologique des échecs de l'antibiothérapie prescrite pour l'OMA a été mise en place dans la région parisienne : 293 enfants ont été inclus par 12 ORL. Au moment de l'échec, la paracentèse et le prélèvement bactériologique n'ont pas retrouvé de bactérie chez 146 patients (49,8 %) et une (ou plusieurs) bactérie potentiellement pathogène chez 147 enfants. S. pneumoniae a été la bactérie le plus fréquemment retrouvée (n = 81 soit 55,1 % des cas bactériologiquement documentés) et le sérotype 23F était prédominant, représentant 53 % de tous les pneumocoques isolés. 70/81 des pneumocoques isolés (86,4 %), étaient résistants ou avaient une sensibilité diminuée à l'antibiotique prescrit. L'amoxicilline semble être l'antibiotique oral le plus efficace sur ces souches. Il semble exister une bonne corrélation entre des index inhibiteurs sériques bas et les échecs. La multirésistance de S. pneumoniae pose des problèmes thérapeutiques sérieux et doit rendre la paracentèse et le prélèvement bactériologique obligatoires en cas d'échec de l'antibiothérapie.
Due to their very different etiological agents, community-acquired pneumoniae in children frequently require empiric antibiotic therapy in emergency. Streptococcus pneumoniae represents between 15 to 30 % of the etiologies and has unspecific diagnostic procedures ; as a matter of fact radiological lobar consolidation is seen in less than half of cases, and laboratory data, except for high procalcitonin level, are poorly reliable. Pneumonia due to Mycoplasma pneumoniae is frequent after 2 years of age, reaching 40 to 60 % of causes in ambulatory teenagers ; it must be treated with macrolides as sequellae are possible. The exact number of viral pneumonia is difficult to establish because of the lack of reliable diagnostic methods. If bacterial superinfections are probably overestimated during acute phase, viral infections may lead to bacterial pneumonia 2 to 4 weeks after the initial episode. Empiric antibiotic treatment must take into account pneumococci and their penicillin– resistant strains. Amoxicillin is the antibiotic of choice, having a higher efficacy on resistant pneumococci than oral cephalosporins. In case of clinical failure of amoxicillin, mycoplasma infection must be considered and patient must receive macrolides. Future epidemiology will be affected by anti-pneumococcal immunisation but difficulties in diagnosis and empiric antibiotic treatment will probably remain. Studies in immunised children are needed to evaluate the importance of pneumococcal infections due to serotypes not included in the vaccine.
The emergence of resistance has imposed a modification of the protocols for the treatment of Streptococcus pneumoniae (S pneumoniae) bacterial meningitis. Amoxicillin is no longer adapted. As resistance to C3G appeared, a synergistic effect of an association C3G + vancomycine was demonstrated. Thus currently this association should be recommended in any case of meningitis supposedly due to S pneumoniae. The treatment is then modified according to the evolution and the minimal inhibition concentration (MIC) of the bacteria. The strains carrying a high level of resistance to cephalosporin (MIC ≥ 4 μg ml–1) or tolerant to vancomycine may cause a therapeutic failure despite an increase of the dosage of cephalosporin. Rifampicin, fosfomycine, or imipenem (despite its risk of convulsions), may represent alternative options, as long as we do not have safe quinolones active on resistant strains of S. pneumoniae. Dexamethasone has been formerly implicated in the relapse of pneumococcal meningitis. Furthermore, its use is questionable since no evidence of a therapeutic benefit has been clearly demonstrated. As a consequence of the resistance phenomenon the management of S. pneumoniae meningitis must include particular measures: at least resistance to penicillin must be checked by the oxacilline disk and the MIC to C3G must be measured by E test; aCSF sample should be obtained between 36 and 48 hours following the beginning of the treatment to ckeck its sterilization. All recent studies have shown a similar prognosis of meningitis due to resistant S. pneumoniae as compared to those due to sensitive strains. However, these data should be interpreted with caution since in these studies, pneumococcus resistant to cephalosporin (the real problem) are not separated from those only resistant to penicillin. Furthermore, presently, the incidence of strains highly resistant to cephalosporin is still low. The new conjugated vaccine against pneumococcus should change the situation if its ability to prevent the circulation of resistant strains is confirmed.
A retrospective survey has been conducted in the Pediatric Intensive Care Units (PICUs) affiliated to the Groupe Francophone d'Urgence et de Réanimation Pédiatrique over two years (1999 and 2000). The purpose was to determine the number of children aged from 10 days to 18 years who died from community acquired bacterial infections and to compare the data to those obtained from official surveys (statistics of death from the Institut National de la Santé et de la Recherche Médicale) and from the Institut National de Veille Sanitaire as well as from punctual studies. Thirty two (60%) PICUs have participated and 100 cases of children without known risk factors, dead from community acquired documented bacterial infection have been considered for analysis (36 in 1999, 54 in 2000). Infants aged between 10 days and 2 months represent 13 of the fatalities. Neisseria meningitidis is the first pathogen responsible for death (34% including 10 not documented cases of purpura fulminans). B group is predominent (1424) compared to the C group (6 cases). A lethal infection due to W135 group occured in 2 infants in 2000. Streptococcus pneumoniae is the second pathogen responsible for death (28%). None of the cases were due to antibiotic resistant pneumococcus. Bordetella pertussis is surprisingly the third pathogen responsible for death (13%), all of them being younger than 2 months. Pertussis is the first cause of death in infants aged 10 days - 2 months. An important increase was observed between 1999 (3 cases) and 2000 (10 cases). Meningitis is the first disease responsible for death (42%): 26 are related to pneumococcus, 5 to meningococcus and 6 to group B streptococcus. Purpura fulminans is the second cause (30%), due mainly to group B meningococus (11 cases). Group C meningococus accounts for 6 cases only. One case is related to pneumococcus. Lung infections are a rare cause of death (5 cases) and particulary staphylococcal pleuro pneumonia seems to be no longer a significative cause of fatality. Toxic shock syndrome is an emergent disease responsible for 5 death (2 staphylococcal, 3 streptococcal). These data fit with those provided by the Institut National de Veille Sanitaire with respect to meningococcal infections and the Renacoq network with respect to pertussis, as well as the data provided by a previous GPIP survey on pneumococcal meningitis. However, the data provided by INSERM seem not to be relevant. In spite of the bias due to a retrospective study and the lack of exhaustivity, this survey provides data which could help decision making with respect to new vaccines against pneumococcus.
Streptococcus pneumoniae resistance to beta-lactams and macrolides has reached high rates in some countries and led to the development of new fluoroquinolones, active against these strains. Streptococcus pneumoniae resistance to these compounds is due to target modifications (DNA gyrase, topo-isomerase IV) and/or increased active efflux (extruding antibiotics out of the bacteria). A Canadian study published in 1999 reported an increased frequency of ciprofloxacin resistant strains from 0% in 1993 to 1.7% in 1997–1998. Other epidemiological studies, made until 2001 worldwide, on several thousand strains, showed that the resistance to respiratory fluoroquinolones such as levofloxacin, moxifloxacin, or gatifloxacin in Streptococcus pneumoniae had reached only 0 to 1.8% in various European countries, including France and in America and Australia. In Asia, resistance reached 0.5 to 3.9% except in Hong Kong where it reached 8%. Right now, these results allow to remain optimistic. In order to maintain this situation and to prolonge the effectiveness of antibiotics, instructions for adequate antibiotic therapy should be applied. In addition, surveillance of antibiotic consumption and resistance should be permanently implemented.
Method. – The in vitro activity of telithromycin was compared to that of betalactams and macrolides on bacteria isolated from respiratory tract in adults. The study involved 30 centers in France in 2000–2001. MICs were determined by the agar dilution method in a central laboratory.Results. – Twenty-eight point three per cent and 22.7% of the Streptococcus pneumoniae strains (n = 675) were of intermediate susceptibility and resistant to penicillin respectively, and 47.7% were resistant to macrolides. Seventeen per cent of penicillin resistant strains were resistant to amoxicillin. Ninety-eight point eight per cent of S. pneumoniae strains were susceptible to telithromycin, and no resistant strain was isolated. Most erythromycin resistant S. pneumoniae carried the ermB gene. MICs 50 and 90 of telithromycin were respectively 1 and 2mg l–1 for Haemophilus influenzae (n = 751). Thirty-three per cent of H. influenzae strains were beta-lactamase producing. Ninety-two per cent of Moraxella catarrhalis strains (n = 268) were beta-lactamase producing, and most strains were susceptible to the antibiotics tested.Comments. – The results of this study confirm the high prevalence of resistance to betalactams and macrolides amongst S. pneumoniae in France. The activity of telithromycin against respiratory bacteria, especially resistant pneumococci, is very interesting from the therapeutic point of view in the scope of its indications and national recommendations.
Streptococcus pneumoniae colonizes the nasopharynx and remains a major human pathogen despite antibiotic therapy. Pneumococci cause important diseases including pneumonia, bacteremia, meningitis and otitis media. Many pneumococcal virulence factors contribute to the pathogenesis. On the one hand, capsular polysaccharides, PspA and PspC enable pneumococci to escape host defenses. On the other hand, after the lysis induced by LytA, pneumolysin, teichoic acids, lipoteichoic acids and phosphocholine induce inflammatory reactions which are often deleterious for the host. Others factors as CbpA, neuraminidases, PsaA… participate in adherence, colonization and in the first steps of the infection. A better knowledge of pneumococcal pathogenesis and virulence factors will contribute to the development of new drugs or vaccines.
Streptococcus pneumoniae is the most frequently involved pathogen in meningitis developed after ENT diseases. In children, meningitis is often a complication of acute otitis media. In adults, meningitis may occur during otitis media, or during acute or chronic sinusitis, or because of a post traumatic or surgical cerebrospinal fluid leak. It is necessary to search for the cause of meningitis because specific follow-up and treatment is required. During meningitis following infectious disease of the upper respiratory tract, surgery may be rapidly indicated if medical antibiotic treatment fails. This surgery will be absolutely necessary only in meningitis complication of chronic diseases. A cerebrospinal fluid leak is to be suspected in recurrent pneumococcal meningitis.
Context.-The spread of drug-resistant Streptococcus pneumoniae in the community is a public health problem in developed and developing nations, but whether antibiotic use is responsible for the increase in drug resistance is not known. Objective.-To analyze the relationship between penicillin-resistant S pneumoniae (PRSp) pharyngeal carriage and characteristics of beta-lactam use. Design.-Observational study of children attending 20 randomly sampled schools. Setting.-The Loiret, in the center of France. Participants.-A total of 941 children, 3 to 6 years old. Main Outcome Measure(s).-Pharyngeal carriage of S pneumoniae, antibiotic use, and medical events during the preceding 30 days. Pneumococcal penicillin G sodium minimal inhibitory concentrations and serotyping were performed. Results.-Medical illnesses and the use of antibiotics were not associated with PRSp carriage. However, oral beta-lactam use was associated with an increased risk of PRSp carriage (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.1-8.3; P=.03). Children treated by low daily doses of an oral beta-lactam (defined as lower than clinical recommendations) had an increased risk of PR,Sp carriage, as compared with children who did not (OR, 5.9; 95% CI, 2.1-16.7; P=.002). A treatment of long duration (>5 days) with a beta-lactam was associated with an increased risk of PRSp carriage (OR, 3.5; 95% CI, 1.3-9.8; P=.02). Conclusions.-Our results suggest that a low daily dose and a long duration of treatment with an oral beta-lactam contribute to the selective pressure in promoting pharyngeal carriage of PRSp.
Streptococcus pneumoniae colonizes the nasopharynx and remains a major human pathogen despite antibiotic therapy. Pneumococci cause important diseases including pneumonia, bacteremia, meningitis and otitis media. Many pneumococcal virulence factors contribute to the pathogenesis. On the one hand, capsular polysaccharides, PspA and PspC enable pneumococci to escape host defenses. On the other hand, after the lysis induced by LytA, pneumolysin, teichoic acids, lipoteichoic acids and phosphocholine induce inflammatory reactions which are often deleterious for the host. Others factors as CbpA, neuraminidases, PsaA... participate in adherence, colonization and in the first steps of the infection. A better knowledge of pneumococcal pathogenesis and virulence factors will contribute to the development of new drugs or vaccines. (C) 2002 Editions scientifiques et medicales Elsevier SAS.
Objective – To assess the importance of procalcitonin (PCT) in pneumonia, PCT was compared to other blood markers, C-reactive protein (CRP), interleukin 6 (IL6), and interferon-alpha (INFα). This prospective study was performed in the emergency room on 88 children (two months–13 years) hospitalized for severe community-acquired pneumonia.Patients – S. Pneumoniae was isolated in ten patients' blood culture, 15 patients a probable bacterial pneumonia according to sputum analysis (14 S. Pneumoniae, 1 Haemophilus influenza b), ten patients a Mycoplasma pneumoniae infection, and 37 others were infected with viruses, eight of whom with a bacterial co-infection. In 16 patients, no causal agent was identified.Results – PCT was always > 2 μg/L in the ten patients with blood culture positive for S. pneumoniae and CRP was > 60 mg/L in 8/10. PCT was > 1 μg/L in 86% of all patients with probable bacterial infection (including Mycoplasma). CRP concentrations of 20 mg/L had a similar sensitivity but a much lower specificity than PCT (40% vs. 86%) to discriminate between bacterial and viral causes of pneumonia. Specificity and sensitivity of IL6 were lower in all cases. Interferon-alpha is a good marker of viral pneumonia but biological assessment requires two days or more.Conclusions – PCT concentrations, with a threshold of 1 μg/L provides better sensitivity and specificity in emergency room than CRP, IL6, INFα, or white blood cell count to differentiate bacterial and viral causes of community-acquired pneumonia in hospitalized children.
Objective. To determine the efficacy, safety and immunogenicity of the heptavalent CRM197 pneumococcal conjugate vaccine against invasive disease caused by vaccine serotypes and to determine the effectiveness of this vaccine against clinical episodes of otitis media.
Methods. The Wyeth Lederle Heptavalent CRM197 (PCV) was given to infants at 2, 4, 6 and 12 to 15 months of age in a double blind trial; 37 868 children were randomly assigned 1:1 to receive either the pneumococcal conjugate vaccine or meningococcus type C CRM197 conjugate. The primary study outcome was invasive disease caused by vaccine serotype. Other outcomes included overall impact on invasive disease regardless of serotype, effectiveness against clinical otitis media visits and episodes, impact against frequent and severe otitis media and ventilatory tube placement. In addition the serotype-specific efficacy against otitis media was estimated in an analysis of spontaneously draining ears.
Results. In the interim analysis in August, 1998, 17 of the 17 cases of invasive disease caused by vaccine serotype in fully vaccinated children and 5 of 5 of partially vaccinated cases occurred in the control group for a vaccine efficacy of 100%. Blinded case ascertainment was continued until April, 1999. As of that time 40 fully vaccinated cases of invasive disease caused by vaccine serotype had been identified, all but 1 in controls for an efficacy of 97.4% (95% confidence interval, 82.7 to 99.9%), and 52 cases, all but 3 in controls in the intent-to-treat analysis for an efficacy of 93.9% (95% confidence interval, 79.6 to 98.5%). There was no evidence of any increase of disease caused by nonvaccine serotypes. Efficacy for otitis media against visits, episodes, frequent otitis and ventilatory tube placement was 8.9, 7.0, 9.3 and 20.1% with P < 0.04 for all. In the analysis of spontaneously draining ears, serotype-specific effectiveness was 66.7%.
Conclusion. This heptavalent pneumococcal conjugate appears to be highly effective in preventing invasive disease in young children and to have a significant impact on otitis media.
The diagnosis of infection by Streptococcus pneumoniae is an important task for microbiology laboratories in view of its prevalence, high mortality and the recent spread of penicillin resistance. ELISA, CIE, LA and CoAG methods have been described for the detection of capsular polysaccharide (CPS) and C-polysaccharide (PnC) in sputum and all have similar sensitivity. Antigen detection in serum has a low diagnostic yield unless bacteraemia is present. Detection of antigen in urine is more sensitive but the need to concentrate the specimen has limited the application of this technique in routine practice. The polymerase chain reaction for an autolysin gene shows promise for diagnosis in blood and sputum.
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Polysaccharide antigens are large molecules consisting of repeating epitopes which are not processed by antigen-presenting cells (APC) but interact directly with B cells, inducing antibody synthesis in the absence of T cells (thus designated T-independent antigens). T cells can influence the antibody response to certain polysaccharides, such as the capsular polysaccharide of S. pneumoniae type 3 [6], but an absolute requirement for T cells has not been demonstrated. T-independent responses are restricted in a number of ways. Most importantly, they fail to induce significant and sustained amounts of antibody in young children below the age of 18 months [7, 8]. While polysaccharides are immunogenic in older children and adults, the characteristics of the antibody responses are rather restricted. They are dominated by IgM and IgG2, are relatively short lived and a booster response cannot be elicited on repeated exposure [7[8]–9]. This failure to induce immunological memory is also reflected in the absence of demonstrable affinity maturation [10]. In contrast to polysaccharides, antibody responses to protein antigens have an absolute requirement for T cells. The consequence of this T cell help are that antibody responses to protein antigens can be elicited in the very young and immunity is long lived due the generation of immunological memory. Antibody responses to protein antigens are dominated by the IgG1 and IgG3 subclasses and affinity maturation can be demonstrated over time.
We reviewed 71 consecutive patients with Streptococcus pneumoniae bacteremia. The patients were analyzed by age, sex, ethnic background, and clinical presentation. Laboratory data reviewed included a CBC count, electrolyte levels, liver function studies, chest radiograph, HIV status, a sputum culture and Gram's stain, and sensitivities for the S pneumoniae isolated. Modalities of therapy, response to treatment, and ultimate outcome were examined. Many of the patients with pneumococcal bacteremia did not have cough, fever, or chills. HIV positivity was a risk factor for pneumococcal infection although it was not associated with increased mortality. Mortality correlated with elderly status, leukopenia, and lack of fever. Many patients had symptoms suggestive of atypical pneumonia including myalgia and mental status change. Hyponatremia and hyperbilirubinemia were commonly noted.
Multiple antimicrobial resistance in pneumococci was detected in Johannesburg in July, 1977, and prompted an investigation of the prevalence of resistant strains in two hospitals. Carriers of Types 6A and 19A penicillin-resistant pneumococci, resistant to antibiotic concentrations ranging between 0.12 and 4 microgram per milliliter were found in 29 per cent of 543 pediatric patients and 2 per cent of 434 hospital staff members. Multiply resistant Type 19A strains, resistant to beta-lactam antibiotics, erythromycin, clindamycin, tetracycline and chloramphenicol, were isolated from 128 carriers, and were responsible for bacteremia in four patients. Isolates from 40 other carriers were resistant to penicillin alone or to penicillin and chloramphenicol or to penicillin, chloramphenicol and tetracycline. Pneumococci can be screened for penicillin resistance with a modified Kirby--Bauer technic; the strains with zones of less than 35 mm around 6-microgram penicillin disks or less than 25 mm around 5-microgram methicillin disks should be tested for sensitivity to penicillin by measurements of minimum inhibitory concentration.
The patterns of colonization of D. pneumoniae were studied over a 46-month period in a group of young children in a day-care center. Forty-four percent of nasal cultures yielded D. pneumoniae. The most frequently isolated serotypes--6, 19, and 23--accounted for 49% of the isolates; the nine most common serotypes included 80% of the isolates. Individual serotypes frequently were carried for several months. Reacquisition of a serotype previously carried occurred frequently. There was limited spread of serotypes among the children despite prolonged contact.
The mechanisms by which Streptococcus pneumoniae spreads from person to person are poorly understood. In this study. optimal methods for sampling. isolation, and identification
of S. pneumoniae from healthy carriers were investigated. Factors influencing carriage rates were analyzed. Findings included the importance
of pharyngeal rather than of nasal sampling in adults, the greater sensitivity of mouse inoculation compared with direct streaking
of blood agar plates, and the superiority of the Quellung reaction with omniserum over the optochin disk as a means of identification
of S. pncumoniae, Carriage rates were highest in children of preschool (35%) or grammar school (29%) age and in adults with preschool children
in the family (18%). Rates were lowest in adults without preschool children in the family (2%–9%).
To study the epidemiology of childhood pneumococcal invasive infections in Israel as a background for immunization programs.
A 2-year (October 1988 through September 1990) prospective, nationwide surveillance of all invasive pediatric pneumococcal infections.
All 25 medical centers hospitalizing children in Israel, including all laboratories performing blood cultures from pediatric patients.
Infants and children aged 0 to 12 years visiting the pediatric emergency department or hospitalized in pediatric departments were included if Streptococcus pneumoniae was isolated from blood or cerebrospinal fluid.
Four hundred sixty-nine invasive infections were diagnosed. Pneumonia, bacteremia without apparent focus, meningitis, and cellulitis were found in 39%, 37%, 17%, and 3%, respectively. The annual incidence was 42 per 100,000 for children younger than 5 years of age (104 per 100,000 for those < 12 months old). The two most common serotypes were 1 and 5, which are rare in Western Europe and North America. Eight groups comprised 82% of all invasive infections. Extrapolated to a population in which 100,000 live births occur yearly, the total annual hospitalizations for pneumococci infections was calculated to be 1928 days. The overall case-fatality rate was 2.2%, but it was 30% during the first month of life.
Pneumococcal invasive infections are common in children in Israel and carry considerable morbidity.