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1.
Vaccine ; 39(2): 372-379, 2021 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-33308889

RESUMEN

BACKGROUND: Changes in serotype distribution have been described after the switch from the 13-valent pneumococcal conjugate vaccine (PCV13) to the 10-valent pneumococcal conjugate vaccine (PCV10) in Belgium. AIM: To describe serotype's invasive disease potential and the detailed evolution of serotype distribution and antimicrobial susceptibility of pneumococcal isolates (carriage and IPD) in children up to 30 months of age over a period during and after the vaccine switch (2015-2018). METHODS: S. pneumoniae strains isolated from the nasopharynx of healthy children attending day-care centres (DCCs) and strains from normally sterile sites of children with IPD were serotyped (Quellung-reaction) and antimicrobial susceptibility testing was performed. Invasive disease potential was defined as the serotype-specific odds ratio (OR). RESULTS: The highly invasive (OR > 1) serotypes 12F, 1, 3, 24A/B/F, 33F, 19A, and 9N were not frequently carried (<7.5% of carriage strains). Different serotypes dominated in carriage (23B, 23A, 11A, 15B) versus IPD (12F, 19A, 10A, 33F). PCV13 vaccine serotypes increased in carriage (5.4% (25/463) in period 1 vs 10.3% (69/668) in period 3) and in IPD (7.3% (8/110 in period 1 vs 23.9% (34/142) in period 3) due to an increase (p < 0.01) in serotype 19A. The penicillin non-susceptibility of 19A was lower (p = 0.02) in carriage (6.8%) than in IPD (23.5%). Erythromycin and tetracycline non-susceptibility were more frequent (p < 0.01) in IPD (26.0%; 23.0%) compared to carriage strains (18.2%; 14.5%) and penicillin non-susceptibility increased over the three year study period (carriage: 13.4%, 19.8%, 18.5%, p = 0.05; IPD: 11.8%, 15.0%, 20.4%, p = 0.02). CONCLUSION: Only some of the serotypes with high invasive disease potential (serotype 1, 3, 19A) in Belgium are included in PCV10 and/or PCV13. This reinforces the need for continuous monitoring, both in healthy children as in children with IPD, to better understand the dynamics of pneumococcal disease, to optimise the composition and implementation of PCVs.

2.
Lancet Infect Dis ; 2020 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-32702303

RESUMEN

BACKGROUND: Ten-valent and 13-valent pneumococcal conjugate vaccines (PCVs) have shown important benefits by decreasing invasive pneumococcal disease caused by vaccine serotypes. Belgium had an uncommon situation with sequential use of PCV7, PCV13, and PCV10 in the childhood vaccination programmes between 2007 and 2018. We aimed to analyse the changes in incidence of invasive pneumococcal disease and serotype distribution in children throughout this period. METHODS: Streptococcus pneumoniae isolates were obtained from patients with invasive pneumococcal disease in Belgium between 2007 and 2018 by the national laboratory-based surveillance. Paediatric invasive pneumococcal disease incidence, serotype distribution, and antimicrobial susceptibility were analysed in periods during which PCV7 (2009-10), PCV13 (2013-14), both PCV13 and PCV10 (2015-16), and PCV10 (2017-18) were used. Incidence rates and trends were compared. Vaccination status was collected. For a subset of serotype 19A isolates, multilocus sequence type was identified. FINDINGS: After a decrease in PCV7 serotype invasive pneumococcal disease was observed during the PCV7 period, total paediatric invasive pneumococcal disease incidence significantly declined during the PCV13 period (-2·6% monthly, p<0·0001). During the PCV13-PCV10 period (2015-16), the lowest mean in paediatric invasive pneumococcal disease incidence was achieved, but the incidence increased again during the PCV10 period (2017-18), especially in children younger than 2 years (+1·7% monthly; p=0·028). This increase was mainly due to a significant rise in serotype 19A invasive pneumococcal disease incidence in the PCV10 period compared with the PCV13 period (p<0·0001), making serotype 19A the predominant serotype in paediatric invasive pneumococcal disease in the PCV10 period. Genetic diversity within the 2017-18 serotype 19A collection was seen, with two predominant clones, ST416 and ST994, that were infrequently observed before PCV10 introduction. In 2018, among children younger than 5 years with invasive pneumococcal disease who were correctly vaccinated, 37% (37 of 100) had PCV13 serotype invasive pneumococcal disease, all caused by serotype 19A and serotype 3. INTERPRETATION: After a significant decrease during the PCV13 period, paediatric invasive pneumococcal disease incidence increased again during the PCV10 period. This observation mainly resulted from a significant increase of serotype 19A cases. During the PCV10 period, dominant serotype 19A clones differed from those detected during previous vaccine periods. Whether changes in epidemiology resulted from the vaccine switch or also from natural evolution remains to be further elucidated. FUNDING: The Belgian National Reference is funded by the Belgian National Institute for Health and Disability Insurance and the whole genome sequencing by an investigator-initiated research grant from Pfizer.

3.
Acta Clin Belg ; : 1-8, 2020 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-32000622

RESUMEN

Objectives: Our aim was to compare serotype distribution in invasive pneumococcal disease (IPD) in the Belgian population before and after introduction of the 13-valent conjugte vaccine (PCV13) in the national childhood vaccination schedule.Methods: Serotyping was performed on 12,534 pleural fluid and bacteraemic Streptococcus pneumoniae isolates sent to the National Reference Centre. We compared the distribution of serotypes (ST)/serogroups (SG) between the periods before (2007-2010) and after (2012-2015) the introduction of PCV13, in children and adults of different age groups, including older individuals (65-84 and ≥85 years).Results: The introduction of PCV13 in the childhood immunization program resulted in a reduction of 16% of all IPD-isolates. The prevalence of PCV13-SG decreased in all age groups: from 81% to 53% (p < 0.0001) in children <18 years, and from 69% to 53% (p < 0.0001) in individuals aged 18-64. This effect was also observed in age groups 65-84 (64% to 50%, p < 0.0001) and ≥85 years (63% to 47%; p < 0.0001). The proportion of IPD cases caused by non-PCV13 SG increased from 31% to 49% between the two periods, indicating replacement with non-vaccine SG. The coverage rate for the 23-valent polysaccharide vaccine (PPV23) in all age groups remains as high as 89% for the total group.Conclusion: After introduction of PCV13, a reduction of PCV13-serotypes occurred in IPD in all age groups. This supports the rationale to combine the effect of PCV13 with the broader coverage of PPV23 as a vaccination strategy for adults.

4.
Euro Surveill ; 25(5)2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-32046817

RESUMEN

BackgroundThe current carriage study was set up to reinforce surveillance during/after the PCV13-to-PCVC10 switch in Belgium.AimThis observational study monitored carriage of Streptococcus pneumoniae (Sp) serotypes, particularly those no longer covered (3, 6A, 19A), as well as Haemophilus influenzae (Hi), because PCV10 contains the non-typeable Hi protein D.MethodsA total of 2,615 nasopharyngeal swabs from children (6-30 months old) attending day care were collected in three periods over 2016-2018. Children's demographic and clinical characteristics and vaccination status were obtained through a questionnaire. Sp and Hi were identified by culture and PCR. Pneumococcal strains were tested for antimicrobial (non-)susceptibility by disc diffusion and serotyped by Quellung-reaction (Quellung-reaction and PCR for serotypes 3, 6A, 19A).ResultsThe carriage prevalence of Sp (> 75%) remained stable over the successive periods but that of Hi increased (87.4%, 664 Hi-carriers/760 in 2016 vs 93.9%, 895/953 in 2017-2018). The proportion of non-PCV13 vaccine serotypes decreased (94.6%, 438 isolates/463 in 2016 vs 89.7%, 599/668 in 2017-2018) while that of PCV13-non-PCV10 vaccine serotypes (3 + 6A + 19A) increased (0.9%, 4 isolates/463 in 2016 vs 7.8%, 52/668 in 2017-2018), with serotype 19A most frequently identified (87.9%, 58/66 isolates). Non-susceptibility of pneumococci against any of the tested antibiotics was stable over the study period (> 44%).ConclusionsDuring and after the PCV13-to-PCV10 vaccine switch, the proportion of non-PCV13 serotypes decreased, mainly due to a serotype 19A carriage prevalence increase. These results complement invasive pneumococcal disease surveillance data, providing further basis for pneumococcal vaccination programme policy making.


Asunto(s)
Portador Sano/microbiología , Haemophilus influenzae/aislamiento & purificación , Nasofaringe/microbiología , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/microbiología , Vacunas Neumococicas/administración & dosificación , Streptococcus pneumoniae/aislamiento & purificación , Antibacterianos/farmacología , Bélgica/epidemiología , Portador Sano/epidemiología , Portador Sano/inmunología , Preescolar , Farmacorresistencia Bacteriana , Femenino , Haemophilus influenzae/efectos de los fármacos , Haemophilus influenzae/inmunología , Humanos , Programas de Inmunización/estadística & datos numéricos , Lactante , Masculino , Pruebas de Sensibilidad Microbiana , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/prevención & control , Prevalencia , Serogrupo , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/inmunología , Vacunación
5.
Malar J ; 19(1): 25, 2020 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-31941497

RESUMEN

BACKGROUND: Blackwater fever (BWF), one of the most severe and life-threatening forms of falciparum malaria, is characterized by acute massive intravascular haemolysis, often leading to acute renal failure. Thus far, the genetics of the underlying susceptibility to develop BWF is not fully elucidated. Deficiency in the MBL protein, an important component of the innate immune system, has previously been suggested to be a susceptibility factor for the development of severe malaria. This study aimed to evaluate the association between MBL2 gene polymorphisms, known to affect the MBL protein level/activity, and the occurrence of BWF among Congolese children. METHODS: This is a case-control study. Cases were patients with BWF, whereas controls, matched for gender and age, had uncomplicated malaria (UM). Dried blood spot was collected for genotyping. RESULTS: A total of 129 children were screened, including 43 BWF and 86 UM. The common allele in BWF and UM was A, with a frequency of 76.7 and 61.0%, respectively (OR: 2.67 (0.87-829) and p = 0.079). The frequency of the C allele was 18.6 and 29.1% in BWF and UM groups, respectively, with p = 0.858. Not a single D allele was encountered. Genotype AA was at higher risk for BWF whereas genotypes A0 (AB and AC) were over-represented in UM group (OR: 0.21 (0.06-0.78)) with p = 0.019. Nine haplotypes were observed in this study: 3 high MBL expression haplotypes and 6 low MBL expression haplotype. One new haplotype HYPC was observed in this study. None of these haplotypes was significantly associated with BWF. CONCLUSION: This pilot study is a preliminary research on MBL2 gene and infectious diseases in DRC. The study results show a higher risk for BWF in AA. This suggests that future studies on BWF should further investigate the contribution of a strong immune response to the occurrence of BWF.


Asunto(s)
Fiebre Hemoglobinúrica/epidemiología , Fiebre Hemoglobinúrica/genética , Lectina de Unión a Manosa/genética , Polimorfismo Genético , Adolescente , Alelos , Fiebre Hemoglobinúrica/orina , Estudios de Casos y Controles , Niño , Preescolar , Estudios de Cohortes , ADN/genética , ADN/aislamiento & purificación , República Democrática del Congo/epidemiología , Femenino , Frecuencia de los Genes , Técnicas de Genotipaje , Haplotipos , Hemoglobinuria/diagnóstico , Hemoglobinuria/orina , Humanos , Modelos Logísticos , Masculino
6.
Acta Clin Belg ; 75(4): 284-292, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31057053

RESUMEN

OBJECTIVES: In prosthetic joint infections (PJIs), there is no consensus about the utility of the preoperative joint aspiration culture to guide antimicrobial treatment. The main objective of this retrospective study was to investigate the value of these preoperative samples to narrow immediate postoperative empirical antimicrobial treatment in patients with a knee or hip PJI. METHODS: Adult patients admitted for an exchange procedure between June 2007 and July 2016 for whom a preoperative joint aspiration within 6 months prior to the procedure was available and with an antibiotic-free interval before sampling, were eligible. Per PJI, taking both preoperative joint aspiration and intraoperative deep samples into account, causative pathogen(s) were assessed by the current Infectious Diseases Society of America (IDSA) guidelines. Per PJI, agreement of preoperative joint aspiration cultures corresponding to the causative pathogen(s) was investigated both on species and on Gram/fungi level. RESULTS: From the 85 PJIs, on species level, the total agreement was found in 58 (68%) PJIs. On Gram/fungi level, when preoperative joint aspiration cultures yielded exclusively Gram-positive microorganisms (n = 61), a 100% predictive value for Gram positive causing pathogens was attained. Insufficient predictive value was observed in PJIs with preoperative joint aspiration yielding Gram-negative microorganisms (n = 4), a fungus (n = 1) or with sterile results (n = 19). CONCLUSION: In the immediate postoperative setting, the treating team might consider a broad spectrum empirical antibiotic regime, guided by the local epidemiology and susceptibility, which can be narrowed to Gram-positive coverage if preoperative joint aspiration cultures yield exclusively Gram-positive microorganisms.

7.
Eur J Clin Microbiol Infect Dis ; 39(1): 53-63, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31624985

RESUMEN

Rapid pathogen identification (ID) and antimicrobial susceptibility testing (AST) of bacteria-causing bloodstream infections can improve patients' outcome. In this study, we evaluated the performance of Alfred60AST (Alifax) which provides AST directly on positive blood culture (BC) bottles by light scattering. In a selected group of patients with a clinical suspicion of severe sepsis or at risk for infections with multiresistant organisms, we compared Alfred60AST AST results with traditional AST results (Vitek2 (bioMérieux) or disk diffusion). Discrepancy analysis was performed by Etest (bioMérieux) or broth microdilution. In total, 222 samples were evaluated. On 595 susceptibility determinations, 93.4% showed categorical agreement (CA) with the standard method. Eighty-one percent of isolates showed a 100% categorical agreement (CA) which increased to 84.3% after discrepancy analysis. There were 8 very major discrepancies (VMD), 18 major discrepancies (MD), and 13 minor discrepancies (MiD). Most discrepant results were observed for piperacillin-tazobactam (15.6%) and clindamycin (18.9%). Analysis time was 6-6.5 h for a complete Alfred60AST AST result. In addition, we evaluated the behavior of clinicians in adjusting antibiotic therapy according to the routine AST results. In 37% of all patients, antibiotic therapy was altered after reporting of AST result and adjustment was more frequent for Gram-negative than for Gram-positive isolates. With some improvements, Alfred60AST provides accurate and rapid preliminary AST results for organisms causing bloodstream infections and may have at least a potential clinical benefit in about one-third of patients with severe sepsis, by delivering faster results compared with conventional methods.


Asunto(s)
Antibacterianos/farmacología , Cultivo de Sangre/métodos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Pruebas de Sensibilidad Microbiana/instrumentación , Adulto , Bacteriemia/microbiología , Pruebas Antimicrobianas de Difusión por Disco/normas , Dispersión Dinámica de Luz , Femenino , Infecciones por Bacterias Gramnegativas/sangre , Infecciones por Bacterias Gramnegativas/microbiología , Humanos , Masculino , Pruebas de Sensibilidad Microbiana/métodos , Sepsis/microbiología , Factores de Tiempo
8.
Open Forum Infect Dis ; 6(6): ofz259, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31263735

RESUMEN

Background: There is a scarcity of data on pneumococcal serotypes carried by children in Ethiopia. We studied pneumococcal nasopharyngeal carriage rate, serotypes, and risk factors among children with community acquired pneumonia (CAP). Methods: A prospective observational cohort study was performed in children with CAP, aged 0-15 years, in 2 pediatric emergency departments in Addis Ababa, Ethiopia. Nasopharyngeal swabs were cultured, and serotypes of Streptococcus pneumoniae were determined by sequencing the cpsB gene and by the Quellung reaction. Risk factors were analyzed by using binary logistic regression. Results: Nasopharyngeal swabs were collected from 362 children with CAP. Pneumococcal carriage rate was 21.5% (78 of 362). The most common serotypes were 19A (27%), 16F (8.5%), and 6A (4.9%). In addition, 8.5% of the pneumococcal isolates were nontypeable. In bivariate analysis, children with a parent that smokes were more likely to carry pneumococci (crude odds ratio, 3.9; 95% confidence interval [CI], 1.2-12.3; P = .023) than those with parents that do not smoke. In multivariable analysis, living in a house with ≥2 rooms (adjusted odds ratio [AOR], 0.48; 95% CI, 0.28-0.82; P = .007) and vaccination with ≥2 doses of 10-valent pneumococcal conjugate vaccine (PCV10) (AOR, 0.37; 95% CI, 0.15-0.92; P = .033) were protective of pneumococcal carriage. Conclusions: Five years after introduction of PCV10 in Ethiopia, the vaccine-related serotype 19A was predominant in the nasopharynx of children with CAP. Continued evaluation of the direct and indirect impact of PCV10 on pneumococcal serotype distribution in Ethiopia is warranted.

9.
Vaccine ; 37(8): 1080-1086, 2019 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-30665775

RESUMEN

BACKGROUND: A three year pneumococcal carriage study was set up in Belgium when the vaccination programme switched from a 13-valent (PCV13) to a 10-valent (PCV10) vaccine. We compared the first follow-up period (October 2016 - June 2017, year 2, Y2) for nasopharyngeal carriage, serotype distribution and antimicrobial susceptibility of S. pneumoniae with the baseline (January-July 2016, year 1, Y1). MATERIALS/METHODS: A single nasopharyngeal swab was taken in children (6-30 months), either attending one of the 112 day-care centres (DCCs), or visiting one of the 21 physicians for an acute otitis media (AOM). S. pneumoniae were cultured, screened for antimicrobial susceptibility, and serotyped. RESULTS: In Y2, 1218 samples were collected. The majority of the Y2-children (>85%) was vaccinated appropriately for their age. Children in Y2 received either PCV13 only (DCC: 23.5%; AOM: 24.6%), PCV10 only (DCC: 29.8%; AOM: 37.7%), or a mix of both vaccines (DCC: 31.9%; AOM: 25.4%). Pneumococcal carriage rates were high (Y2, DCC: 68.2%; AOM: 64.8%). Among carriers, prevalence of PCV13 serotypes was low (Y2 vs Y1, DCC: 3.5% vs 5.4%; AOM: 7.6% vs 7.7%). Although prevalence of PCV13-non-PCV10 serotypes did not increase significantly compared to Y1 (Y2 vs Y1, DCC: 1.6% vs 0.9%; Y2 vs Y1, AOM: 5.1% vs 0.0%), the proportion of serotypes 3, 6A, 19A among PCV13 serotype carriers in DCC was significantly higher in Y2 (46.2% vs Y1: 16.0%, p-value = 0.034). Serotypes 23B and 15B were the predominant non-vaccine serotypes (Y2). Among detected strains, non-susceptibility to at least one of five antibiotics tested (penicillin, tetracycline, erythromycin, levofloxacin, cotrimoxazole) was comparable to Y1 (Y2 vs Y1, DCC: 41.3% vs 42.4%; AOM: 49.4% vs 48.1%). CONCLUSION: After completion of the PCV13-to-PCV10 vaccine switch in Belgium, the proportion of PCV13-non-PCV10 serotypes (mainly 19A) significantly increased among PCV13 serotype carriers in DCC, stressing the need for strengthened surveillance as the PCV10-vaccinated population grows.


Asunto(s)
Antibacterianos/inmunología , Portador Sano/inmunología , Infecciones Neumocócicas/inmunología , Vacunas Neumococicas/inmunología , Bélgica , Portador Sano/microbiología , Preescolar , Femenino , Estudios de Seguimiento , Vacuna Neumocócica Conjugada Heptavalente/inmunología , Humanos , Lactante , Masculino , Otitis Media/inmunología , Otitis Media/microbiología , Serogrupo , Streptococcus pneumoniae/inmunología , Vacunas Conjugadas/inmunología
10.
PLoS One ; 13(7): e0199427, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29979689

RESUMEN

BACKGROUND: The Belgian Superior Health Council (SHC) recently added a 13-valent pneumococcal conjugate vaccine (PCV13) to its recommendations for adult pneumococcal vaccination. This study addresses the policy question regarding whether a single dose of PCV13 should be reimbursed among Belgian adults aged 65-84 years with chronic comorbidities ("moderate-risk") or immunosuppression ("high-risk"). METHODS: A cohort model was developed to project lifetime risks, consequences, and costs of invasive pneumococcal disease (IPD) and pneumococcal community-acquired pneumonia (CAP). Parameter values were estimated using published literature and available databases, and were reviewed by Belgian experts. PCV13 effectiveness was assumed to be durable during the first 5 years following receipt, and to progressively decline thereafter with 15 years protection. The Belgian National Health Insurance perspective was employed. RESULTS: Use of PCV13 (vs. no vaccine) in moderate/high-risk persons aged 65-84 years (n = 861,467; 58% vaccination coverage) would be expected to prevent 527 cases of IPD, 1,744 cases of pneumococcal CAP and 176 pneumococcal-related deaths, and reduce medical care costs by €20.1 million. Vaccination costs, however, would increase by €36.9 million and thus total overall costs would increase by €16.8 million. Cost per QALY gained was €17,126. In probabilistic sensitivity analyses, use of PCV13 was cost-effective in 97% of 1,000 simulations. CONCLUSIONS: Reimbursement of PCV13 in moderate/high-risk Belgian adults aged 65-84 years would be cost-effective from the Belgian healthcare perspective.


Asunto(s)
Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/inmunología , Streptococcus pneumoniae/inmunología , Factores de Edad , Anciano , Anciano de 80 o más Años , Bélgica/epidemiología , Análisis Costo-Beneficio , Femenino , Costos de la Atención en Salud , Humanos , Masculino , Evaluación de Resultado en la Atención de Salud , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/economía , Vigilancia en Salud Pública , Medición de Riesgo , Factores de Riesgo
12.
Thromb Haemost ; 118(5): 818-829, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29614521

RESUMEN

BACKGROUND: Staphylococcus aureus (S. aureus) bacteraemia is frequent and carries a high morbidity and mortality. Coagulases secreted by S. aureus initiate blood coagulation by directly activating prothrombin. This pathogen-activated coagulation is insensitive to most antithrombotic drugs, with the exception of small molecule direct thrombin inhibitors (DTIs). DTIs inhibit the coagulase-prothrombin complex, or staphylothrombin, and improve outcome in preclinical models of S. aureus infection. OBJECTIVE: A single-centre, randomized, controlled feasibility and safety trial of staphylothrombin inhibition with DTIs in patients with S. aureus bacteraemia. PATIENTS AND METHODS: Consecutive eligible adult patients with S. aureus positive blood cultures in the University Hospitals Leuven (Belgium) were randomized 1:1 to DTI (oral dabigatran 110 mg twice daily or intravenous argatroban according to activated partial thromboplastin time [aPTT]) for 7 to 10 days, or subcutaneous enoxaparin 40 mg once daily. Primary outcomes were feasibility and safety of DTI in patients with S. aureus bacteraemia. Secondary outcomes include D-dimer evolution (day 0-4) as marker of coagulation activation; inflammatory and microbiological parameters; and clinical outcomes including metastatic infections. RESULTS: Thirty-one percent (94/303) of screened patients were enrolled. Dabigatran plasma levels inhibited staphylothrombin. Clinically relevant bleeding (5/47 vs. 5/47) and thrombotic (7/47 vs. 7/47) complications were similar in both groups. Coagulase inhibition with DTIs was associated with a trend towards faster D-dimer decrease at day 4 (-662 ± 249 ng/mL vs. -40 ± 213 ng/mL for DTI-treated patients vs. control; p = 0.06) and a numerically lower number of persistently positive blood cultures. No differences in inflammatory parameters or other clinical outcomes were observed. CONCLUSION: Targeting staphylothrombin with DTIs is feasible in a subset of S. aureus bacteraemic patients, with comparable safety to standard thromboprophylaxis. In future studies of staphylothrombin inhibition, feasibility can be further improved by rapid diagnostics and by strategies without concomitant anticoagulant effect.


Asunto(s)
Anticoagulantes/administración & dosificación , Antitrombinas/administración & dosificación , Bacteriemia/tratamiento farmacológico , Coagulasa/antagonistas & inhibidores , Dabigatrán/administración & dosificación , Enoxaparina/administración & dosificación , Ácidos Pipecólicos/administración & dosificación , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Trombina/antagonistas & inhibidores , Trombosis/prevención & control , Administración Intravenosa , Administración Oral , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Antitrombinas/efectos adversos , Arginina/análogos & derivados , Bacteriemia/diagnóstico , Bacteriemia/microbiología , Bélgica , Coagulación Sanguínea/efectos de los fármacos , Coagulasa/metabolismo , Dabigatrán/efectos adversos , Enoxaparina/efectos adversos , Estudios de Factibilidad , Femenino , Hemorragia/inducido químicamente , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Tiempo de Tromboplastina Parcial , Proyectos Piloto , Ácidos Pipecólicos/efectos adversos , Estudios Prospectivos , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/enzimología , Sulfonamidas , Trombina/metabolismo , Trombosis/sangre , Trombosis/diagnóstico , Trombosis/microbiología , Factores de Tiempo , Resultado del Tratamiento
13.
Hum Vaccin Immunother ; 14(5): 1218-1229, 2018 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-29420161

RESUMEN

Streptococcus pneumoniae causes a high disease burden including pneumonia, meningitis and septicemia. Both a polysaccharide vaccine targeting 23 serotypes (PPV23) and a 13-valent conjugate vaccine (PCV13) are indicated for persons aged over 50 years. We developed and parameterized a static multi-cohort model to estimate the incremental cost-effectiveness and budget-impact of these vaccines at different uptake levels. Using three different vaccine efficacy scenarios regarding non-invasive pneumococcal pneumonia and extensive uni- and multivariate sensitivity analyses, we found a strong preference for PPV23 over PCV13 in all age groups at willingness to pay levels below €300 000 per quality adjusted life year (QALY). PPV23 vaccination would cost on average about €83 000, €60 000 and €52 000 per QALY gained in 50-64, 65-74 and 75-84 year olds, whereas for PCV13 this is about €171 000, €201 000 and €338 000, respectively. Strategies combining PPV23 and PCV13 vaccines were most effective but generally less cost-effective. When assuming a combination of increased duration of PCV13 protection, increased disease burden preventable by PCV13 and a 75% reduction of the PCV13 price, PCV13 could become more attractive in <75 year olds, but would remain less attractive than PPV23 from age 75 years onwards. These observations are independent of the assumption that PPV23 has 0% efficacy against non-invasive pneumococcal pneumonia. Pneumococcal vaccination would be most cost-effective in Belgium, when achieving high uptake with PPV23 in 75-84 year olds, as well as by negotiating a lower market-conform PPV23 price to improve uptake and cost-effectiveness.


Asunto(s)
Análisis Costo-Beneficio , Infecciones Neumocócicas/economía , Vacunas Neumococicas/economía , Vacunación/economía , Factores de Edad , Anciano , Anciano de 80 o más Años , Bélgica/epidemiología , Costo de Enfermedad , Femenino , Accesibilidad a los Servicios de Salud/economía , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/microbiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/uso terapéutico , Años de Vida Ajustados por Calidad de Vida , Streptococcus pneumoniae/inmunología , Vacunación/métodos , Vacunas Conjugadas/economía , Vacunas Conjugadas/uso terapéutico
14.
Vaccine ; 36(1): 15-22, 2018 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-29180027

RESUMEN

BACKGROUND: In Belgium, the infant pneumococcal conjugate vaccine (PCV) programme changed from PCV7 (2007-2011) to PCV13 (2011-2015) and to PCV10 (2015-2016). A 3-year nasopharyngeal carriage study was initiated during the programme switch in 2016. Main objective of the year 1 assessment was to obtain a baseline measurement of pneumococcal carriage prevalence, carriage density, serotype distribution and antibiotic resistance. MATERIALS/METHODS: Two infant populations aged 6-30 months and without use of antibiotics in the seven days prior to sampling were approached: (1) attending one of 85 randomly selected day-care centres (DCC); (2) presenting with AOM at study-trained general practitioners and paediatricians. Demographic and clinical characteristics were documented and a single nasopharyngeal swab was taken. S. pneumoniae were cultured, screened for antibiotic resistance and serotyped, and quantitative Taqman real-time PCR (qRT-PCR) targeting LytA was performed. RESULTS: Culture-based (DCC: 462/760; 60.8% - AOM: 27/39; 69.2%) and LytA-based (DCC: 603/753; 80.1% - AOM: 32/39; 82.1%) carriage prevalence was high. Average pneumococcal DNA load in LytA-positive day-care samples was 6.5 × 106 copies/µl (95%CI = 3.9-9.2 × 106, median = 3.5 × 105); DNA load was positively associated with signs of common cold and negatively with previous antibiotic use. Culture-based frequency of 13 pneumococcal vaccine (PCV) serotypes was 5.4% in DCC and 7.7% in AOM, with 19F and 14 being most frequent, and frequencies below 0.5% for serotypes 3, 6A, 19A in both populations. Predominant non-PCV serotypes were 23B and 23A in day-care and 11A in infants with AOM. In day-care, resistance to penicillin was rare (<0.5%) and absent against levofloxacin; 32.7% and 16.9% isolates were cotrimoxazole- and erythromycin-resistant respectively. CONCLUSION: Four years after PCV13 introduction in the vaccination programme, PCV13 serotype carriage was rare in infants throughout Belgium and penicillin resistance was rare. Continued surveillance in the context of a PCV programme switch is necessary.


Asunto(s)
Portador Sano/epidemiología , Programas de Inmunización/estadística & datos numéricos , Nasofaringe/microbiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Streptococcus pneumoniae/aislamiento & purificación , Antibacterianos/efectos adversos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Portador Sano/microbiología , Jardines Infantiles/estadística & datos numéricos , Preescolar , Farmacorresistencia Bacteriana Múltiple , Femenino , Vacuna Neumocócica Conjugada Heptavalente/administración & dosificación , Vacuna Neumocócica Conjugada Heptavalente/inmunología , Humanos , Lactante , Masculino , Pruebas de Sensibilidad Microbiana , Otitis Media/microbiología , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/inmunología , Vacunas Neumococicas/inmunología , Reacción en Cadena de la Polimerasa , Prevalencia , Serogrupo , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/inmunología , Factores de Tiempo
15.
Int J Antimicrob Agents ; 51(4): 562-570, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29180278

RESUMEN

Recent studies suggest that intensive care unit patients treated with amikacin frequently do not attain the desired pharmacokinetic/pharmacodynamic (PK/PD) target, i.e. peak amikacin concentration (Cpeak) to minimum inhibitory concentration (MIC) ratio of ≥8, when a single dose of 15 mg/kg is used. No data are available for patients admitted to the emergency department (ED). The aim of this prospective randomised controlled study was to determine PK/PD target attainment in ED patients presenting with severe sepsis or septic shock treated with 15 mg/kg versus 25 mg/kg amikacin. Patients were randomly assigned to receive amikacin 25 mg/kg or 15 mg/kg. Amikacin Cpeak values were determined. The primary outcome was target attainment defined as Cpeak/MIC ≥ 8 both using EUCAST susceptibility breakpoints and actually documented MICs as denominator. A total of 104 patients were included. The EUCAST-based target was attained in 76% vs. 40% of patients assigned to the 25 mg/kg vs. 15 mg/kg dose groups (P <0.0001). Target attainment using actual MICs (median of 2 mg/L, documented in 48 isolated Gram-negative pathogens) was achieved in 95% vs. 94% of patients in the 25 mg/kg vs. 15 mg/kg dose groups (P = 0.969). Risk factors associated with PK/PD target failure were identified in the multivariable analysis. At least 25 mg/kg amikacin as a single dose should be used in ED patients with severe sepsis and septic shock to attain the EUCAST-based PK/PD target. However, when using local epidemiology as denominator, 15 mg/kg appears to be sufficient. [ClinicalTrials.gov ID: NCT02365272.


Asunto(s)
Amicacina/farmacocinética , Amicacina/uso terapéutico , Antibacterianos/farmacocinética , Antibacterianos/uso terapéutico , Choque Séptico/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Amicacina/administración & dosificación , Antibacterianos/administración & dosificación , Cuidados Críticos , Relación Dosis-Respuesta a Droga , Servicio de Urgencia en Hospital , Enterobacteriaceae/efectos de los fármacos , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Estudios Prospectivos , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa/efectos de los fármacos , Choque Séptico/microbiología
16.
Gut ; 66(1): 79-88, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-26423113

RESUMEN

OBJECTIVE: Pouchitis is the most common complication after colectomy with ileal pouch-anal anastomosis (IPAA) for UC and the risk is the highest within the 1st year after surgery. The pathogenesis is not completely understood but clinical response to antibiotics suggests a role for gut microbiota. We hypothesised that the risk for pouchitis can be predicted based on the faecal microbial composition before colectomy. DESIGN: Faecal samples from 21 patients with UC undergoing IPAA were prospectively collected before colectomy and at predefined clinical visits at 1 month, 3 months, 6 months and 12 months after IPAA. The predominant microbiota was analysed using community profiling with denaturing gradient gel electrophoresis followed by quantitative real-time PCR validation. RESULTS: Cluster analysis before colectomy distinguished patients with pouchitis from those with normal pouch during the 1st year of follow-up. In patients developing pouchitis, an increase of Ruminococcus gnavus (p<0.001), Bacteroides vulgatus (p=0.043), Clostridium perfringens (p=0.011) and a reduction of two Lachnospiraceae genera (Blautia (p=0.04), Roseburia (p=0.008)) was observed. A score combining these five bacterial risk factors was calculated and presence of at least two risk factors showed a sensitivity and specificity of 100% and 63.6%, respectively. CONCLUSIONS: Presence of R. gnavus, B. vulgatus and C. perfringens and absence of Blautia and Roseburia in faecal samples of patients with UC before surgery is associated with a higher risk of pouchitis after IPAA. Our findings suggest new predictive and therapeutic strategies in patients undergoing colectomy with IPAA.


Asunto(s)
Colitis Ulcerosa/microbiología , Colitis Ulcerosa/cirugía , ADN Bacteriano/análisis , Heces/microbiología , Reservoritis/microbiología , Adulto , Bacteroidetes/genética , Bacteroidetes/aislamiento & purificación , Clostridium perfringens/genética , Clostridium perfringens/aislamiento & purificación , Análisis por Conglomerados , Reservorios Cólicos/efectos adversos , Ácidos Grasos Volátiles/análisis , Heces/química , Femenino , Microbioma Gastrointestinal/genética , Humanos , Complejo de Antígeno L1 de Leucocito/análisis , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Periodo Preoperatorio , Proctocolectomía Restauradora/efectos adversos , Estudios Prospectivos , Ruminococcus/genética , Ruminococcus/aislamiento & purificación , Factores de Tiempo
17.
Acta Clin Belg ; 72(5): 331-335, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27765000

RESUMEN

We report a case of a 77-year old male who developed a fulminant erysipelas and sepsis, caused by Myroides odoratimimus. Selecting the optimal antibiotic therapy for the treatment of infections with M. odoratimimus is challenging due to limited clinical experience with this micro-organism and its reported multidrug-resistance. Review of previous studies concerning in vitro antibacterial susceptibility and clinical experience with M. odoratimimus resulted in six case reports describing bacteremia, soft tissue and bone infections, pneumonia and urinary tract infections. In vitro susceptibility to aminoglycosides, fluoroquinolones and trimethoprim/sulfamethoxazole is variable. Treatment of M. odoratimimus infections should be based on antimicrobial susceptibility testing results. In a majority of the case reports, including the present one, treatment with fluoroquinolones proved to be a good therapeutic option.


Asunto(s)
Antibacterianos/uso terapéutico , Erisipela/tratamiento farmacológico , Infecciones por Flavobacteriaceae/tratamiento farmacológico , Fluoroquinolonas/uso terapéutico , Sepsis/tratamiento farmacológico , Anciano , Erisipela/microbiología , Humanos , Masculino , Sepsis/microbiología
18.
19.
PLoS One ; 11(5): e0154816, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27227336

RESUMEN

We present the results of a longitudinal surveillance study (1995-2014) on fluoroquinolone resistance (FQ-R) among Belgian non-invasive Streptococcus pneumoniae isolates (n = 5,602). For many years, the switch to respiratory fluoroquinolones for the treatment of (a)typical pneumonia had no impact on FQ-R levels. However, since 2011 we observed a significant decrease in susceptibility towards ciprofloxacin, ofloxacin and levofloxacin with peaks of 9.0%, 6.6% and 3.1% resistant isolates, respectively. Resistance to moxifloxacin arised sporadically, and remained <1% throughout the entire study period. We observed classical topoisomerase mutations in gyrA (n = 25), parC (n = 46) and parE (n = 3) in varying combinations, arguing against clonal expansion of FQ-R. The impact of recombination with co-habiting commensal streptococci on FQ-R remains marginal (10.4%). Notably, we observed that a rare combination of DNA Gyrase mutations (GyrA_S81L/GyrB_P454S) suffices for high-level moxifloxacin resistance, contrasting current model. Interestingly, 85/422 pneumococcal strains display MICCIP values which were lowered by at least four dilutions by reserpine, pointing at involvement of efflux pumps in FQ-R. In contrast to susceptible strains, isolates resistant to ciprofloxacin significantly overexpressed the ABC pump PatAB in comparison to reference strain S. pneumoniae ATCC 49619, but this could only be linked to disruptive terminator mutations in a fraction of these. Conversely, no difference in expression of the Major Facilitator PmrA, unaffected by reserpine, was noted between susceptible and resistant S. pneumoniae strains. Finally, we observed that four isolates displayed intermediate to high-level ciprofloxacin resistance without any known molecular resistance mechanism. Focusing future molecular studies on these isolates, which are also commonly found in other studies, might greatly assist in the battle against rising pneumococcal drug resistance.


Asunto(s)
Transportadoras de Casetes de Unión a ATP/genética , Proteínas Bacterianas/genética , Girasa de ADN/genética , Farmacorresistencia Bacteriana/genética , Fluoroquinolonas/farmacología , Mutación Missense , Streptococcus pneumoniae , Sustitución de Aminoácidos , Bélgica/epidemiología , Farmacorresistencia Bacteriana/efectos de los fármacos , Femenino , Humanos , Estudios Longitudinales , Masculino , Infecciones Neumocócicas/tratamiento farmacológico , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/genética , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/aislamiento & purificación
20.
Vaccine ; 34(18): 2106-12, 2016 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-26988257

RESUMEN

BACKGROUND: A recent trial demonstrated the 13 valent conjugate pneumococcal vaccine (PCV13) to be effective against invasive and non-invasive pneumococcal disease in healthy adults. PCV13 might therefore be considered as an alternative to the 23 valent polysaccharide vaccine (PPV23). AIM: To explore the cost-effectiveness of vaccinating healthy adults over 50, with either PCV13 or PPV23 alone, or with a combined strategy using both PCV13 and PPV23. METHODS: A static multi-cohort model was developed simulating the consequences of pneumococcal vaccination in adults over 50 from a health care payer's perspective, for different scenarios of duration of vaccine protection and serotype evolution. RESULTS: At currently expected prices, PCV13 vaccination of healthy adults over 50 is unlikely to be cost-effective either compared with no vaccination or in combination with PPV23 versus PPV23 only. CONCLUSION: Further research is needed on vaccine efficacy of the combination strategy and of risk groups, as well as the duration of vaccine protection. Serotype evolutions under the influence of the childhood PCV program should be closely monitored.


Asunto(s)
Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/uso terapéutico , Vacunación/economía , Anciano , Anciano de 80 o más Años , Bélgica , Análisis Costo-Beneficio , Humanos , Persona de Mediana Edad , Modelos Teóricos , Vacunas Neumococicas/economía
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