Influència dels serotips dels Streptococcus pneumoniae en l’evolució clínica de les pneumònies.

Estudi retrospectiu en el que es descriuen les característiques clíniques de pacients adults amb pneumònia causada per Streptococcus pneumoniae aïllats en mostres invasives i la influència dels serotips amb elevada capacitat de causar malaltia invasiva en l'evolució clínica d’aquestes. Es divideixen en 2 grups: en el grup E s’inclouen pacients infectats amb serotips amb elevada capacitat invasiva i en el grup X s’engloba a la resta. Els pacients del grup E són més joves i la mortalitat d’aquest grup és significativament més baixa (p = 0,022). No es troben diferències entre els grups en relació a comorbiditats i evolució clínica.

Usefulness of betalactam therapy for community-acquired pneumonia in the era of drug-resistant Streptococcus pneumoniae: a randomized study of amoxicillin-clavulanate and ceftriaxone

Empirical antibiotic therapy of community-acquired pneumonia (CAP) has been complicated by the worldwide emergence of penicillin resistance among Streptococcus pneumoniae. The impact of this resistance on the outcome of patients hospitalized for CAP, empirically treated with betalactams, has not been evaluated in a randomized study. We conducted a prospective, randomized trial to assess the efficacy of amoxicillin-clavulanate (2 g/200 mg/8 hr) and ceftriaxone (1 g/24 hr) in a cohort of patients hospitalized for moderate-to-severe CAP. Three-hundred seventy-eight patients were randomized to receive amoxicillin-clavulanate (184 patients) or ceftriaxone (194 patients). Efficacy was assessed on Day 2, after completion of therapy and at long term follow-up. There were no significant differences in outcomes between treatment groups, both in intention-to-treat and per-protocol analysis. Overall mortality was 10.3% for amoxicillin-clavulanate and 8.8% for ceftriaxone (NS). There were 116 evaluable patients with proven pneumococcal pneumonia. Rates of high-level penicillin resistance (MIC of penicillin ≥2 µg/mL) were similar in the two groups (8.2 and 10.2%). Clinical efficacy at the end of therapy was 90.6% for amoxicillin-clavulanate and 88.9% for ceftriaxone (95% C.I. of the difference: -9.3 to +12.7%). No differences in outcomes were attributable to differences in penicillin susceptibility of pneumococcal strains. Sequential i.v./oral amoxicillin-clavulanate and parenteral ceftriaxone were equally safe and effective for the empirical treatment of acute bacterial pneumonia, including penicillin and cephalosporin-resistant pneumococcal pneumonia. The use of appropriate betalactams in patients with penumococcal pneumonia and in the overall CAP population, is reliable at the current level of resistance

The hpx genetic system for hypoxanthine assimilation as a nitrogen source in Klebsiella pneumoniae: gene organization and transcriptional regulation.

Growth experiments showed that adenine and hypoxanthine can be used as nitrogen sources by several strains of K. pneumoniae under aerobic conditions. The assimilation of all nitrogens from these purines indicates that the catabolic pathway is complete and proceeds past allantoin. Here we identify the genetic system responsible for the oxidation of hypoxanthine to allantoin in K. pneumoniae. The hpx cluster consists of seven genes, for which an organization in four transcriptional units, hpxDE, hpxR, hpxO and hpxPQT, is proposed. The proteins involved in the oxidation of hypoxanthine (HpxDE) or uric acid (HpxO) did not display any similarity to other reported enzymes known to catalyze these reactions, but instead are similar to oxygenases acting on aromatic compounds. Expression of the hpx system is activated by nitrogen limitation and by the presence of specific substrates, with hpxDE and hpxPQT controlled by both signals. Nitrogen control of hpxPQT transcription, which depends on 54, is mediated by the Ntr system. In contrast, neither NtrC nor NAC is involved in the nitrogen control of hpxDE, which is dependent on 70 for transcription. Activation of these operons by the specific substrates is also mediated by different effectors and regulatory proteins. Induction of hpxPQT requires uric acid formation, whereas expression of hpxDE is induced by the presence of hypoxanthine through the regulatory protein HpxR. This LysR-type regulator binds to a TCTGC-N4-GCAAA site in the intergenic hpxD-hpxR region. When bound to this site for hpxDE activation, HpxR negatively controls its own transcription.

Emerging, non-PCV13 serotypes 11A and 35B of Streptococcus pneumoniae show high potential for biofilm formation in vitro

Background: Since the use of pneumococcal conjugate vaccines PCV7 and PCV13 in children became widespread, invasive pneumococcal disease (IPD) has dramatically decreased. Nevertheless, there has been a rise in incidence of Streptococcus pneumoniae non-vaccine serotypes (NVT) colonising the human nasopharynx. Nasopharyngeal colonisation, an essential step in the development of S. pneumoniae-induced IPD, is associated with biofilm formation. Although the capsule is the main pneumococcal virulence factor, the formation of pneumococcal biofilms might, in fact, be limited by the presence of capsular polysaccharide (CPS). Methodology/Principal Findings: We used clinical isolates of 16 emerging, non-PCV13 serotypes as well as isogenic transformants of the same serotypes. The biofilm formation capacity of isogenic transformants expressing CPSs from NVT was evaluated in vitro to ascertain whether this trait can be used to predict the emergence of NVT. Fourteen out of 16 NVT analysed were not good biofilm formers, presumably because of the presence of CPS. In contrast, serotypes 11A and 35B formed >45% of the biofilm produced by the non-encapsulated M11 strain. Conclusions/Significance This study suggest that emerging, NVT serotypes 11A and 35B deserve a close surveillance.

Factores pronósticos de mortalidad de la neumonía neumocócica grave en la UCI

Estudi retrospectiu realitzat en dos centres hospitalaris durant el període 1996-2009, per valorar els factors pronòstics de mortalitat a la pneumònia pneumocòccica greu. Van ser inclosos 70 pacients ingressats a unitats de cures intensives amb Streptococcus pneumoniae aïllat a cultiu de sang i amb criteris de pneumònia greu segons la American Thoracic Society. Al nostre estudi, la resistència als macròlids i una alta puntuació als índexs de gravetat APACHE II, SOFA i PSI son factors associats a un major risc de mortalitat en pacients amb pneumònia pneumocòccica greu.

Relación de Citoquinas y Biomarcadores como patrones de inflamación y etiología de la neumonía adquirida en la comunidad”

La neumonía adquirida en la comunidad (NAC) es una enfermedad respiratoria infecciosa muy prevalente y de elevada mortalidad que desencadena inflamación sistémica. Las últimas investigaciones analizan la respuesta inflamatoria y han observado que la infección por determinados microorganismos se caracterizaría por un “patrón” de respuesta inflamatoria. Nuestro estudio analizó la diferente etiología de la NAC y la respuesta inflamatoria (PCR, PCT y citocinas). Concluyó que las NAC causadas por microorganismo conocido presentan un “patrón” de inflamación específico (S. pneumoniae eleva la PCT e IL-6, la Legionella aumenta la PCR), y que la respuesta está incrementada en presencia de bacteriemia.

Estacionalidad de la neumonía adquirida en la comunidad (NAC) y su influencia con el clima

La pneumònia adquirida a la comunitat (PAC) és una patologia molt prevalent, l´etiologia de la qual ve donada per les característiques de la regió geogràfica, de l'agent causal i del pacient. L'estudi de cadascuna d'elles és fonamental per al seu correcte abordatge terapèutic. Ens vam proposar estudiar els canvis de l'agent causal de la PAC en funció de l'estacionalitat i la influència dels canvis climàtics de la nostra àrea geogràfica. Material i mètode: Estudi prospectiu longitudinal de pacients ingressats per PAC des de Gener de 2008 a Desembre de 2009. Analitzem dades sociodemogràfiques, comorbiditat, gravetat, agent etiològic, complicacions i mortalitat. Correlacionem la temperatura mitjana, la precipitació acumulada mitjana i el caràcter de la precipitació per S. pneumoniae i Legionella pneumophila en cada estació de l'any. Anàlisi estadística: Xi quadrat, t de Student per mostres independents, anàlisi de la variància i correlació de Spearman. Resultats: Incloem 155 pacients, 63.9% homes i 54.8% majors de 65 anys. La major incidència de PAC va ser a l'hivern. Streptococcus pneumoniae va ser l'agent causal més freqüent en totes les estacions de l'any a excepció de l'estiu, que va ser Legionella pneumophila. Observem una correlació significativa entre la menor temperatura mitjana estacional i l'etiologia pneumocòccica i al revés quan l'agent causal va ser Legionella pneumophila. No obstant això, no trobem diferències etiològiques per estacions en relació amb la humitat ambiental. Conclusions: En la nostra àrea, Streptococcus pneumoniae és l'agent etiològic més freqüent a l'hivern amb baixes temperatures mentre que a l'estiu, amb altes temperatures, és Legionella pneumophila.

Paper de l’ Haemophilus influenzae en les exacerbacions de la Malaltia Pulmonar Obstructiva Crònica (MPOC): tipificació molecular i factors de virulència

Objetivos: 1.-Identificar los factores clínicos y microbiológicos que ayuden a predecir la aparición de exacerbaciones en la EPOC. 2.-Diagnóstico y cuantificación de las especies bacterianas aisladas en esputo (fase de exacerbación y estable) .3.- Tipificación genotípica secuencial de las cepas de H. influenzae y P. aeruginosa. 4.- Impacto del tratamiento antibiótico en la aparición de resistencias en estos patógenos. 5.- Diseño: Estudio prospectivo (3 años). Ámbito del estudio: Hospital Universitario de tercer nivel. Pacientes con EPOC grave atendidos en la Consulta Monográfica de EPOC del Servicio de Neumología. Métodos microbiológicos: Cuantificación de la carga bacteriana en muestras respiratorias en fase estable y en exacerbación. Estudio de la sensibilidad “in vitro”. Tipificación molecular (PFGE y MLST) de H. influenzae y P. aeruginosa. Estudio de los genes de virulencia de H. influenzae mediante PCR. Resultados: Desde Febrero de 2010 a Julio de 2011 se han incluido 77 pacientes. Los microorganismos más frecuentemente aislados en fase de exacerbación fueron: P. aeruginosa (29.3%), H. influenzae (15.92%), M. catarrhalis (12.74%), S. pneumoniae (10.19%) y S. aureus (5.10%). En los 88 episodios por P. aeruginosa se detectaron 38 genotipos diferentes. En los 41 episodios por H. influenzae se detectaron 39 genotipos diferentes. El 10% de los episodios fueron polimicrobianos. Los episodios de EAEPOC y de fase estable tuvieron una distribución de microorganismos similar. Sin embargo, cuando se cuantificaron las cargas bacterianas fueron mayores en EAEPOC (intervalo 4x107 -2x108) que en fase estable (intervalo 2x105 -4x107). Conclusiones: El genotipo de las cepas de P. aeruginosa y H. influenzae aisladas en EAEPOC difieren de un paciente a otro, sin embargo la mayoría de los episodios de cada paciente están causados por un genotipo único.

Some pneumococcal serotypes are more frequently associated with relapses of acute exacerbations in COPD patients

Objectives: To analyze the role of the capsular type in pneumococci causing relapse and reinfection episodes of acute exacerbation in COPD patients. Methods: A total of 79 patients with 116 recurrent episodes of acute exacerbations caused by S. pneumoniae were included into this study (1995–2010). A relapse episode was considered when two consecutive episodes were caused by the same strain (identical serotype and genotype); otherwise it was considered reinfection. Antimicrobial susceptibility testing (microdilution), serotyping (PCR, Quellung) and molecular typing (PFGE/MLST) were performed. Results: Among 116 recurrent episodes, 81 (69.8%) were reinfections, caused by the acquisition of a new pneumococcus,and 35 (30.2%) were relapses, caused by a pre-existing strain. Four serotypes (9V, 19F, 15A and 11A) caused the majority (60.0%) of relapses. When serotypes causing relapses and reinfection were compared, only two serotypes were associatedwith relapses: 9V (OR 8.0; 95% CI, 1.34–85.59) and 19F (OR 16.1; 95% CI, 1.84–767.20). Pneumococci isolated from relapses were more resistant to antimicrobials than those isolated from the reinfection episodes: penicillin (74.3% vs. 34.6%, p,0.001), ciprofloxacin (25.7% vs. 9.9%, p,0.027), levofloxacin (22.9% vs. 7.4%, p = 0.029), and co-trimoxazole (54.3% vs. 25.9%, p,0.001). Conclusions: Although the acquisition of a new S. pneumoniae strain was the most frequent cause of recurrences, a third ofthe recurrent episodes were caused by a pre-existing strain. These relapse episodes were mainly caused by serotypes 9V and 19F, suggesting an important role for capsular type

Efficacy and safety of tigecycline versus levofloxacin for community-acquired pneumonia.

Abstract Background: Tigecycline, an expanded broad-spectrum glycylcycline, exhibits in vitro activity against many common pathogens associated with community-acqui red pneumonia (CAP), as well as penetration into lung tissues that suggests effectiveness in ho spitalized CAP patients. The aim of the present study was to compare the efficacy and safety of intravenous (IV) tigecycline with IV levofloxacin in hospitalized adults with CAP. Methods: In this prospective, double-blin d, non-inferiority phase 3 trial, eligible patients with a clinical diagnosis of CAP supported by radiographic evidence were stratified by Fine Pneumonia Severity Index and randomized to tigecycline or levofloxacin for 7-14 days of therapy. Co-primary efficacy endpoints were clinical response in the clinically evaluable (CE) and clinical modified intent- to-treat (c-mITT) populations at te st-of-cure (Day 10-21 post-therapy). Results: Of the 428 patients who received at least on e dose of study drug, 79% had CAP of mild-moderate severity according to their Fine score. Clinical cure rates for the CE population were 88.9% for tigecycline and 85.3% for levofloxac in. Corresponding c-mITT population rates were 83.7% and 81.5%, respectively. Eradication rates for Streptococcus pneumoniae were 92% for tigecycline and 89% for levofloxac in. Nausea, vomiting, and diarrhoea were the most frequently reported adverse events. Rates of premature disc continuation of study drug or study withdrawal because of any adverse event were similar for both study drugs. Conclusion: These findings suggest that IV tigecycline is non-inferior to IV levofloxacin and is generally well-tolerated in the treatment of hospitalized adults with CAP.

Experimental study of clinafloxacin alone and in combination in the treatment of ciprofloxacin-susceptible and -resistant pneumococcal meningitis

The increasing incidence of ciprofloxacin resistance in Streptococcus pneumoniae may limit the efficacy of the new quinolones in difficult-to-treat infections such as meningitis. The aim of the present study was to determine the efficacy of clinafloxacin alone and in combination with teicoplanin and rifampin in the therapy of ciprofloxacin-susceptible and ciprofloxacin-resistant pneumococcal meningitis in rabbits. When used against a penicillin-resistant ciprofloxacin-susceptible strain (Clinafloxacin MIC 0.12 μg/ml), clinafloxacin at a dose of 20 mg/kg per day b.i.d. decreased bacterial concentration by -5.10 log cfu/ml at 24 hr. Combinations did not improve activity. The same clinafloxacin schedule against a penicillin- and ciprofloxacin-resistant strain (Clinafloxacin MIC 0.5 μg/ml) was totally ineffective. Our data suggest that a moderate decrease in quinolone susceptibility, as indicated by the detection of any degree of ciprofloxacin resistance, may render these antibiotics unsuitable for the management of pneumococcal meningitis

Mouthrinses: a comparative microbiological study

This study was performed in order to evaluate the efficacy of different mouthrinses whose use is extended in Spain. Six different antiseptic mouthrinses were studied by means of determination of Minimal Inhibitory Concentration (MIC) values against Klebsiella pneumoniae, Serratia marcescens, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella typhimurium, Bacillus subtilis, Streptococcus mutans, Prevotella intermedia, Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans. Also in vivo experiments were carried out in volunteers by the use of mouthrinses and evaluation of bacterial populations before and after the treatment. Finally, the kinetics of bacterial death was determined. Results suggested that the determination of MIC values is not a reliable method to evaluate the antibacterial effect of such products. On the other hand those rinsing solutions based on the effect of oxygen, such as those containing carbamide peroxide have a greater efficacy against anaerobic bacteria compared with rinses whose active molecule is a disinfectant. Finally, the kinetics of bacterial death demonstrates that the essential oil rinse kills bacteria much faster. All tested mouthrinses were active as antibacterial although those based on oxygen production or essential oils were more active than solutions based on chlorhexidine and Triclosan

Some pneumococcal serotypes are more frequently associated with relapses of acute exacerbations in COPD patients

Objectives: To analyze the role of the capsular type in pneumococci causing relapse and reinfection episodes of acute exacerbation in COPD patients. Methods: A total of 79 patients with 116 recurrent episodes of acute exacerbations caused by S. pneumoniae were included into this study (1995–2010). A relapse episode was considered when two consecutive episodes were caused by the same strain (identical serotype and genotype); otherwise it was considered reinfection. Antimicrobial susceptibility testing (microdilution), serotyping (PCR, Quellung) and molecular typing (PFGE/MLST) were performed. Results: Among 116 recurrent episodes, 81 (69.8%) were reinfections, caused by the acquisition of a new pneumococcus,and 35 (30.2%) were relapses, caused by a pre-existing strain. Four serotypes (9V, 19F, 15A and 11A) caused the majority (60.0%) of relapses. When serotypes causing relapses and reinfection were compared, only two serotypes were associatedwith relapses: 9V (OR 8.0; 95% CI, 1.34–85.59) and 19F (OR 16.1; 95% CI, 1.84–767.20). Pneumococci isolated from relapses were more resistant to antimicrobials than those isolated from the reinfection episodes: penicillin (74.3% vs. 34.6%, p,0.001), ciprofloxacin (25.7% vs. 9.9%, p,0.027), levofloxacin (22.9% vs. 7.4%, p = 0.029), and co-trimoxazole (54.3% vs. 25.9%, p,0.001). Conclusions: Although the acquisition of a new S. pneumoniae strain was the most frequent cause of recurrences, a third ofthe recurrent episodes were caused by a pre-existing strain. These relapse episodes were mainly caused by serotypes 9V and 19F, suggesting an important role for capsular type