RESUMEN
BACKGROUND: Neonatal sepsis is a major cause of morbidity and mortality. It is the third leading cause of neonatal mortality globally constituting 13% of overall neonatal mortality. Despite the high burden of neonatal sepsis, high-quality evidence in diagnosis and treatment is scarce. Due to the diagnostic challenges of sepsis and the relative immunosuppression of the newborn, many neonates receive antibiotics for suspected sepsis. Antibiotics have become the most used therapeutics in neonatal intensive care units, and observational studies in high-income countries suggest that 83% to 94% of newborns treated with antibiotics for suspected sepsis have negative blood cultures. The last Cochrane Review was updated in 2005. There is a need for an updated systematic review assessing the effects of different antibiotic regimens for late-onset neonatal sepsis. OBJECTIVES: To assess the beneficial and harmful effects of different antibiotic regimens for late-onset neonatal sepsis. SEARCH METHODS: We searched the following electronic databases: CENTRAL (2021, Issue 3); Ovid MEDLINE; Embase Ovid; CINAHL; LILACS; Science Citation Index EXPANDED and Conference Proceedings Citation Index - Science on 12 March 2021. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs. SELECTION CRITERIA: We included RCTs comparing different antibiotic regimens for late-onset neonatal sepsis. We included participants older than 72 hours of life at randomisation, suspected or diagnosed with neonatal sepsis, meningitis, osteomyelitis, endocarditis, or necrotising enterocolitis. We excluded trials that assessed treatment of fungal infections. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. We used the GRADE approach to assess the certainty of evidence. Our primary outcome was all-cause mortality, and our secondary outcomes were: serious adverse events, respiratory support, circulatory support, nephrotoxicity, neurological developmental impairment, necrotising enterocolitis, and ototoxicity. Our primary time point of interest was at maximum follow-up. MAIN RESULTS: We included five RCTs (580 participants). All trials were at high risk of bias, and had very low-certainty evidence. The five included trials assessed five different comparisons of antibiotics. We did not conduct a meta-analysis due to lack of relevant data. Of the five included trials one trial compared cefazolin plus amikacin with vancomycin plus amikacin; one trial compared ticarcillin plus clavulanic acid with flucloxacillin plus gentamicin; one trial compared cloxacillin plus amikacin with cefotaxime plus gentamicin; one trial compared meropenem with standard care (ampicillin plus gentamicin or cefotaxime plus gentamicin); and one trial compared vancomycin plus gentamicin with vancomycin plus aztreonam. None of the five comparisons found any evidence of a difference when assessing all-cause mortality, serious adverse events, circulatory support, nephrotoxicity, neurological developmental impairment, or necrotising enterocolitis; however, none of the trials were near an information size that could contribute significantly to the evidence of the comparative benefits and risks of any particular antibiotic regimen. None of the trials assessed respiratory support or ototoxicity. The benefits and harms of different antibiotic regimens remain unclear due to the lack of well-powered trials and the high risk of systematic errors. AUTHORS' CONCLUSIONS: Current evidence is insufficient to support any antibiotic regimen being superior to another. RCTs assessing different antibiotic regimens in late-onset neonatal sepsis with low risks of bias are warranted.
ANTECEDENTES: La sepsis neonatal es una causa importante de morbilidad y mortalidad. Es la tercera causa de mortalidad neonatal a nivel mundial y constituye el 13% de la mortalidad neonatal total. A pesar de la elevada carga de la sepsis neonatal, la evidencia de alta calidad en el diagnóstico y el tratamiento es escasa. Debido a las dificultades de diagnóstico de la sepsis y a la relativa inmunosupresión del neonato, muchos reciben antibióticos por sospecha de sepsis. Los antibióticos se han convertido en el tratamiento más utilizado en las unidades de cuidados intensivos neonatales, y los estudios observacionales realizados en países de ingresos altos indican que entre el 83% y el 94% de los neonatos tratados con antibióticos por sospecha de sepsis tienen hemocultivos negativos. La última revisión Cochrane se actualizó en 2005. Se necesita una revisión sistemática actualizada que evalúe los efectos de los diferentes regímenes de antibióticos para la sepsis neonatal de inicio tardío. OBJETIVOS: Evaluar los efectos beneficiosos y perjudiciales de diferentes regímenes antibióticos para la sepsis neonatal de inicio tardío. MÉTODOS DE BÚSQUEDA: Se hicieron búsquedas en las siguientes bases de datos electrónicas: CENTRAL (2021, número 3); Ovid MEDLINE; Embase Ovid; CINAHL; LILACS; Science Citation Index EXPANDED y Conference Proceedings Citation Index Science el 12 de marzo de 2021. También se buscaron ensayos controlados aleatorizados (ECA) y cuasialeatorizados en las bases de datos de ensayos clínicos y en las listas de referencias de artículos identificados. CRITERIOS DE SELECCIÓN: Se incluyeron ECA que compararon diferentes regímenes de antibióticos para la sepsis neonatal de inicio tardío. Se incluyeron participantes mayores de 72 horas de vida en el momento de la asignación al azar, con sospecha o diagnóstico de sepsis neonatal, meningitis, osteomielitis, endocarditis o enterocolitis necrosante. Se excluyeron los ensayos que evaluaron el tratamiento de las infecciones micóticas. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión, de forma independiente, evaluaron los estudios para inclusión, extrajeron los datos y evaluaron el riesgo de sesgo. Se utilizó el método GRADE para evaluar la certeza de la evidencia. El desenlace principal fue la mortalidad por todas las causas, y los desenlaces secundarios fueron: eventos adversos graves, asistencia respiratoria, apoyo circulatorio, nefrotoxicidad, deterioro del desarrollo neurológico, enterocolitis necrosante y ototoxicidad. El punto temporal principal de interés fue el seguimiento máximo. RESULTADOS PRINCIPALES: Se incluyeron cinco ECA (580 participantes). Todos los ensayos tuvieron alto riesgo de sesgo y evidencia de certeza muy baja. Los cinco ensayos incluidos evaluaron cinco comparaciones diferentes de antibióticos. No se realizó un metanálisis debido a la falta de datos relevantes. De los cinco ensayos incluidos, un ensayo comparó cefazolina más amikacina con vancomicina más amikacina; un ensayo comparó ticarcilina más ácido clavulánico con flucloxacilina más gentamicina; un ensayo comparó cloxacilina más amikacina con cefotaxima más gentamicina; un ensayo comparó meropenem con atención estándar (ampicilina más gentamicina o cefotaxima más gentamicina); y un ensayo comparó vancomicina más gentamicina con vancomicina más aztreonam. Ninguna de las cinco comparaciones encontró evidencia de una diferencia al evaluar la mortalidad por todas las causas, los eventos adversos graves, el apoyo circulatorio, la nefrotoxicidad, el deterioro del desarrollo neurológico o la enterocolitis necrosante; sin embargo, ninguno de los ensayos se acercó a un tamaño de información que pudiera contribuir significativamente a la evidencia de los beneficios y los riesgos comparativos de cualquier régimen antibiótico en particular. Ninguno de los ensayos evaluó la asistencia respiratoria o la ototoxicidad. Los efectos beneficiosos y perjudiciales de los diferentes regímenes de antibióticos aún no están claros debido a la falta de ensayos con un poder estadístico adecuado y al alto riesgo de errores sistemáticos. CONCLUSIONES DE LOS AUTORES: La evidencia actual no es suficiente para apoyar que un régimen de antibióticos sea superior a otro. Se justifica la realización de ECA con bajo riesgo de sesgo que evalúen diferentes regímenes antibióticos en la sepsis neonatal de inicio tardío.
Asunto(s)
Antibacterianos/uso terapéutico , Sepsis Neonatal/tratamiento farmacológico , Amicacina/efectos adversos , Amicacina/uso terapéutico , Ampicilina/efectos adversos , Ampicilina/uso terapéutico , Antibacterianos/efectos adversos , Aztreonam/efectos adversos , Aztreonam/uso terapéutico , Sesgo , Cefazolina/efectos adversos , Cefazolina/uso terapéutico , Ácido Clavulánico/efectos adversos , Ácido Clavulánico/uso terapéutico , Quimioterapia Combinada , Floxacilina/efectos adversos , Floxacilina/uso terapéutico , Gentamicinas/efectos adversos , Gentamicinas/uso terapéutico , Humanos , Recién Nacido , Ensayos Clínicos Controlados Aleatorios como Asunto , Ticarcilina/efectos adversos , Ticarcilina/uso terapéutico , Vancomicina/efectos adversos , Vancomicina/uso terapéuticoRESUMEN
Stenotrophomonas maltophilia (S. maltophilia) is an important nosocomial bacterial pathogen. However, the clinical features of children with S. maltophilia infection, the predisposing factors, and the antibiotic susceptibility of the bacteria have not been fully evaluated.In this study, the data of children with S. maltophilia infection from the West China Second University Hospital of Sichuan University (Chengdu, China) between July 2010 and October 2017 were collected and analyzed. The clinical features of enrolled children, the predisposing factors, and the antibiotic susceptibility were reported.In total, infection of S. maltophilia was identified in 128 patients. Most of these patients were under 1 year old (67.2%) and were mainly diagnosed as pneumonia (69%). A large proportion had underlying diseases (45.3%), received immunosuppressive therapy (53.1%), had undergone invasive operations (41.4%), had a history of carbapenem antibiotics use within 7 days before culture acquisition (54.7%), history of intensive care unit (ICU) hospitalization within previous 30 days (34.4%), and other risk factors. In particular, invasive operation (95% confidence interval [CI]: 1.125-14.324, Pâ=â.032), especially mechanical ventilation (95% CI: 1.277-20.469, Pâ=â.021), and ICU admission (95% CI: 1.743-22.956, Pâ=â.005) were independent risk factors for the children to develop severe S. maltophilia infection. As for antibiotic susceptibility, trimethoprim sulfamethoxazole (TMP-SMX), piperacillin tazobactam, ticarcillin clavulanate, and ceftazidime exhibited strong antibacterial activities against S. maltophilia, the susceptibility rates were 97.5%, 86.7%, 92.9%, and 81.5%, respectively.We report the clinical features of children with S. maltophilia infection, the predisposing factors and the antibiotic susceptibility. TMP-SMX can continue to be the first choice for the treatment of S. maltophilia infection. Piperacillin tazobactam, ticarcillin clavulanate, and the third generation cephalosporins can be used as alternative drugs.
Asunto(s)
Infecciones por Bacterias Gramnegativas/epidemiología , Stenotrophomonas maltophilia , Distribución por Edad , Antibacterianos/uso terapéutico , Carbapenémicos/uso terapéutico , Ceftazidima/uso terapéutico , Preescolar , China/epidemiología , Ácidos Clavulánicos/uso terapéutico , Comorbilidad , Femenino , Infecciones por Bacterias Gramnegativas/diagnóstico , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Hospitalización/estadística & datos numéricos , Humanos , Inmunosupresores/uso terapéutico , Lactante , Unidades de Cuidado Intensivo Pediátrico , Tiempo de Internación/estadística & datos numéricos , Masculino , Combinación Piperacilina y Tazobactam/uso terapéutico , Respiración Artificial/estadística & datos numéricos , Estudios Retrospectivos , Factores de Riesgo , Distribución por Sexo , Procedimientos Quirúrgicos Operativos/estadística & datos numéricos , Ticarcilina/uso terapéutico , Combinación Trimetoprim y Sulfametoxazol/uso terapéuticoRESUMEN
Background: Empirical antibiotherapy (EA) should target all bacteria in post-operative peritonitis (PP). Nevertheless, recent studies failed to prove a link between adequacy of EA and prognosis of PP. We sought to confirm this loss of association between adequate EA and prognosis and to analyze the evolution of patients' characteristics and antimicrobial strategies. Methods: This is was retrospective study. Patients with a positive fungal culture were excluded. The cohort was divided into two time periods. Data of survivors and non-survivors were compared within each time period. Differences between the two periods were assessed. A multivariable analysis searched for parameters associated with a higher hospital mortality rate. Results: Two hundred fifty-one patients were included, with 92 patients in the first period (P1) and 152 patients in the second period (P2). Inadequate EA was associated with a worse outcome only in P1. The multivariable analysis in the whole cohort showed that inadequate EA was associated with a higher mortality rate. When the differences noticed between the two periods were entered in the model (presence of resistant gram-positive cocci and EA comprising glycopeptides), inadequate EA was no longer associated with worse outcome. In P1, the most severe patients had more resistant bacteria, hence, had a higher rate of inadequate EA. This artifact disappeared in P2, during which broader antibiotherapies with triple EA were more often prescribed for the most severe patients. Conclusion: This study showed that the link between inadequate EA and outcome of patients with PP was at least partly artifactual in older studies.
Asunto(s)
Antibacterianos/uso terapéutico , Procedimientos Quirúrgicos del Sistema Digestivo , Mortalidad Hospitalaria , Peritonitis/tratamiento farmacológico , Infección de la Herida Quirúrgica/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Aminoglicósidos/uso terapéutico , Fuga Anastomótica , Líquido Ascítico/microbiología , Ácidos Clavulánicos/uso terapéutico , Estudios de Cohortes , Técnicas de Cultivo , Pruebas Antimicrobianas de Difusión por Disco , Farmacorresistencia Bacteriana Múltiple , Femenino , Fluoroquinolonas/uso terapéutico , Humanos , Imipenem/uso terapéutico , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Análisis Multivariante , Peritonitis/microbiología , Combinación Piperacilina y Tazobactam/uso terapéutico , Complicaciones Posoperatorias , Pronóstico , Estudios Retrospectivos , Infección de la Herida Quirúrgica/microbiología , Ticarcilina/uso terapéutico , Resultado del Tratamiento , Vancomicina/uso terapéuticoRESUMEN
BACKGROUND: While Aspergillus detection rates in adults, adolescents and older children with cystic fibrosis (CF) have increased, the risk of acquiring this fungal pathogen in young children is unknown. AIM: To determine the risk and explanatory factors of acquiring Aspergillus in children with CF by age 5 years. METHODS: Cross-sectional analysis of clinical, bronchoalveolar lavage and treatment data from the Australasian Cystic Fibrosis Bronchoalveolar Lavage study was used to identify predictive factors for detecting Aspergillus at age 5 years. A parametric repeated time-to-event model quantitatively described the risk and factors associated with acquiring Aspergillus and Pseudomonas aeruginosa from birth until age 5 years. RESULTS: Cross-sectional analysis found that the number of P. aeruginosa eradication courses increased the odds of detecting Aspergillus at age 5 years (OR 1.61, 95% CI 1.23 to 2.12). The median (IQR) age for the first P. aeruginosa positive culture was 2.38 (1.32-3.79) years and 3.69 (1.68-4.74) years for the first Aspergillus positive culture. The risk of P. aeruginosa and Aspergillus events changes with time after the first year of study entry. It also decreases for P. aeruginosa after completing P. aeruginosa eradication (HR 0.15, 95% CI 0.00 to 0.79), but increases for Aspergillus events (HR 2.75, 95% CI 1.45 to 5.41). The risk of acquiring both types of events increases after having had a previous event. CONCLUSION: In young children with CF, completing P. aeruginosa eradication therapy and previous Aspergillus events are associated with increased risk of acquiring Aspergillus.
Asunto(s)
Antibacterianos/uso terapéutico , Fibrosis Quística/complicaciones , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/epidemiología , Pseudomonas aeruginosa , Aspergilosis Pulmonar/epidemiología , Antibacterianos/administración & dosificación , Lavado Broncoalveolar , Ceftazidima/uso terapéutico , Preescolar , Ciprofloxacina/uso terapéutico , Ácidos Clavulánicos/uso terapéutico , Estudios Transversales , Femenino , Humanos , Lactante , Estudios Longitudinales , Masculino , Prevalencia , Aspergilosis Pulmonar/diagnóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Recurrencia , Factores de Riesgo , Ticarcilina/uso terapéutico , Tobramicina/uso terapéuticoRESUMEN
OBJECTIVES: The objective of this study was to determine whether intra-aural administration of aqueous solutions of marbofloxacin, gentamicin, tobramycin and ticarcillin (used off-licence) was associated with changes in hearing as measured by brainstem auditory evoked responses. MATERIALS AND METHODS: Dogs diagnosed with otitis media (n=37) underwent brainstem auditory evoked response testing and then were treated for their ear disease. First, the external ear canal and middle ear were flushed with sterile saline followed by EDTA tris with 0·15% chlorhexidine. Then, a combination of aqueous antibiotic mixed with an aqueous solution of EDTA tris was instilled into the middle ear. Follow-up examinations were undertaken for each dog, and treatment was continued until there were no detected infectious organisms or inflammatory infiltrate. Brainstem auditory evoked response testing was repeated after resolution of the infection and discontinuation of therapy. RESULTS: Brainstem auditory evoked responses in dogs treated with aqueous solutions of marbofloxacin or gentamicin remained unchanged or improved after therapy of otitis media but were impaired in dogs treated with ticarcillin or tobramycin. CLINICAL SIGNIFICANCE: If off-licence use of topical antibiotics is deemed necessary in cases of otitis media, aqueous solutions of marbofloxacin and gentamicin appear to be less ototoxic than aqueous solutions of ticarcillin or tobramycin.
Asunto(s)
Antibacterianos/efectos adversos , Pérdida Auditiva/veterinaria , Otitis Media/veterinaria , Administración Tópica , Animales , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Perros , Oído Medio/patología , Potenciales Evocados Auditivos del Tronco Encefálico/efectos de los fármacos , Fluoroquinolonas/administración & dosificación , Fluoroquinolonas/efectos adversos , Fluoroquinolonas/uso terapéutico , Gentamicinas/administración & dosificación , Gentamicinas/efectos adversos , Gentamicinas/uso terapéutico , Pérdida Auditiva/inducido químicamente , Otitis Media/tratamiento farmacológico , Ticarcilina/administración & dosificación , Ticarcilina/efectos adversos , Ticarcilina/uso terapéutico , Tobramicina/administración & dosificación , Tobramicina/efectos adversos , Tobramicina/uso terapéuticoRESUMEN
BACKGROUND: Blood infections with multidrug-resistant Gram-negative carbapenem-resistant bacilli are particularly dangerous and challenging to treat in organ transplant recipients. Resistance to carbapenems may be acquired, for example, in Enterobacteriaceae, Pseudomonas, or Acinetobacter spp. or innate, for example, in Stenotrophomonas maltophilia. The purpose of this study was to analyze blood infections caused by S maltophilia in organ transplant recipients and to compare drug susceptibility of these bacteria and the same species isolated from the blood of other inpatients. METHODS: A total of 26 S maltophilia strains isolated from blood samples of 26 patients (including 14 liver or kidney transplant recipients) hospitalized during 2011 to 2014 were evaluated in this study. Antibiotic susceptibility was determined via E-test and disk diffusion methods. RESULTS: Stenotrophomonas maltophilia strains isolated from blood exhibited sensitivity to trimethoprim/sulfamethoxazole (100%), levofloxacin (96.2%), ciprofloxacin (92.3%), ticarcillin/clavulanic acid (80.8%), and ceftazidime (53.9%). CONCLUSIONS: Because appropriate antibiotic therapy in the case of S maltophilia differs from the standard empirical therapy administered in the case of most other Gram-negative bacilli, early identification of this pathogen is of particular significance. The use of antibiotics to which this pathogen is sensitive eliminates the infection and helps avoid graft loss.
Asunto(s)
Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/microbiología , Pruebas de Sensibilidad Microbiana , Trasplante de Órganos/efectos adversos , Antibacterianos/uso terapéutico , Ceftazidima/uso terapéutico , Ciprofloxacina/uso terapéutico , Ácidos Clavulánicos/uso terapéutico , Farmacorresistencia Bacteriana , Hospitales de Enseñanza , Humanos , Levofloxacino/uso terapéutico , Stenotrophomonas maltophilia , Ticarcilina/uso terapéutico , Receptores de Trasplantes/estadística & datos numéricos , Combinación Trimetoprim y Sulfametoxazol/uso terapéuticoRESUMEN
Achromobacteria are ubiquitous environmental organisms that may also become opportunistic pathogens in certain conditions, such as cystic fibrosis, hematologic and solid organ malignancies, renal failure, and certain immune deficiencies. Some members of this genus, such as xylosoxidans, cause primarily nosocomially acquired infections affecting multiple organ systems, including the respiratory tract, urinary tract, and, less commonly, the cardiovascular and central nervous systems. Despite an increasing number of published case reports and literature reviews suggesting a global increase in achromobacterial disease, most clinicians remain uncertain of the organism's significance when clinically isolated. Moreover, effective treatment can be challenging due to the organism's inherent and acquired multidrug resistance patterns. We reviewed all published cases to date of non-cystic fibrosis achromobacterial lung infections to better understand the organism's pathogenic potential and drug susceptibilities. We found that the majority of these cases were community acquired, typically presenting as pneumonias (88%), and were most frequent in individuals with hematologic and solid organ malignancies. Our findings also suggest that achromobacterial lung infections are difficult to treat, but respond well to extended-spectrum penicillins and cephalosporins, such as ticarcillin, piperacillin, and cefoperazone.
Asunto(s)
Achromobacter/fisiología , Antibacterianos/uso terapéutico , Cefalosporinas/uso terapéutico , Farmacorresistencia Bacteriana/fisiología , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Penicilinas/uso terapéutico , Neumonía Bacteriana/tratamiento farmacológico , Achromobacter/patogenicidad , Factores de Edad , Bronquiectasia/epidemiología , Cefoperazona/uso terapéutico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/epidemiología , Comorbilidad , Femenino , Infecciones por Bacterias Gramnegativas/epidemiología , Humanos , Masculino , Neoplasias/epidemiología , Piperacilina/uso terapéutico , Neumonía Bacteriana/epidemiología , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/epidemiología , Factores de Riesgo , Factores Sexuales , Ticarcilina/uso terapéutico , Factores de VirulenciaRESUMEN
The objective of this study was to evaluate the frequency of Clostridium Difficile Infection (CDI) among kidney transplant recipients and describe the clinical picture in correlation with the presence of certain risk factors. We included kidney transplant recipients with a functioning graft, who were admitted during the period 1/2012-12/2013, and patients with ESRD who were admitted to undergo Kidney Transplantation (KTx) from a deceased or a living donor in the same period. Patients were screened following clinical indication of gastrointestinal infection. CDI diagnosis was based on a positive stool sample for CD toxins and stool culture. Within the period 2012-2013, we recorded 24 cases of CDI in 19 patients, accounting for a frequency of 5.4% of CDI in our population. In addition to diarrhea, 63.15% of the patients presented with fever, 31.25% with anorexia, while abdominal pain was a rare symptom (0.53%). None of the patients had ileus, bowel obstruction or megacolon. Fourteen patients (73.7%) had a history of recent exposure (15 days) to antimicrobial agents prior to the evolution of CDI symptoms. A relapse of the CDI infection was identified in five cases. CDI infection is a significant factor of morbidity in patients with KTx and should be considered in the clinical setting of diarrhea, even in cases with no exposure to antibiotic agents.
Asunto(s)
Clostridioides difficile/aislamiento & purificación , Infecciones por Clostridium/diagnóstico , Infecciones por Clostridium/epidemiología , Enfermedades Renales/cirugía , Trasplante de Riñón , Adulto , Anciano , Antibacterianos/uso terapéutico , Ácido Clavulánico/uso terapéutico , Infecciones por Clostridium/tratamiento farmacológico , Diarrea/tratamiento farmacológico , Diarrea/microbiología , Hospitalización , Humanos , Riñón/microbiología , Riñón/patología , Enfermedades Renales/microbiología , Persona de Mediana Edad , Morbilidad , Estudios Retrospectivos , Factores de Riesgo , Ticarcilina/uso terapéuticoRESUMEN
BACKGROUND: A series of cases of piperacillin-tazobactam (P/T)-associated neutropenia has been observed recently in children in our center. Because neutropenia was seldom observed in children treated with ticarcillin-clavulanic acid (T/C), we conducted a study to determine if there is an increased risk of neutropenia in children exposed to P/T in comparison with T/C. METHODS: Medical records of subjects aged <18 years who received at least 1 dose of P/T or T/C between 1 January 2008 and 30 June 2011 were reviewed. RESULTS: Two hundred ninety-nine episodes of treatment (65 P/T, 234 T/C) met inclusion criteria. Among those episodes, 213 had data allowing complete white blood cell count analysis and were included in the final analysis. Thirteen cases of neutropenia were observed during the study period. The average time to onset was 17.6 days and all patients were aged <13 years. Seven cases (10.8%) occurred in the P/T group and 6 (2.6%) in the T/C group (unadjusted odds ratio, 4.59; 95% confidence interval, 1.48-14.17). Although a statistically significant correlation was observed between age, treatment duration, and total dose and the development of neutropenia (r = -0.121, P = .037; r = 0.267, P < .001; r = 0.260, P < .001, respectively), this was not the case for sex, indications, neutrophil count at initiation, and concomitant drug treatments. CONCLUSIONS: Although our results need to be confirmed, they suggest that children receiving long courses of therapy (>2 weeks) with P/T may be at increased risk of neutropenia, compared with T/C.
Asunto(s)
Antibacterianos/efectos adversos , Neutropenia/inducido químicamente , Neutropenia/epidemiología , Ácido Penicilánico/análogos & derivados , Adolescente , Antibacterianos/uso terapéutico , Niño , Preescolar , Ácidos Clavulánicos/efectos adversos , Ácidos Clavulánicos/uso terapéutico , Estudios de Cohortes , Femenino , Humanos , Lactante , Masculino , Ácido Penicilánico/efectos adversos , Ácido Penicilánico/uso terapéutico , Piperacilina/efectos adversos , Piperacilina/uso terapéutico , Combinación Piperacilina y Tazobactam , Estudios Retrospectivos , Medición de Riesgo , Ticarcilina/efectos adversos , Ticarcilina/uso terapéuticoRESUMEN
OBJECTIVE: Antibiotic administration during acute appendicitis in children continues to be debated. The purpose of this study was to compare efficacy of two prophylactic antibiotic treatment guidelines in acute appendicitis and peritonitis in children. MATERIEL AND METHODS: The infectious complication rate after appendicectomy was compared during two distinct periods (before/after study). During the first period, the guidelines for antibiotic administration were based on ticarcillin-clavulanic acid. During the second period, the guidelines were based on amoxicillin-clavulanic acid for non-perforated appendicitis or appendicitis with localized peritonitis, and clavulanic acid was reserved for general peritonitis. All children younger than 16 years of age who underwent appendicectomy during the periods studied were included. Data were retrospectively collected from surgical and anesthetics charts. RESULTS: Ninety-five children during the first period and 238 during the second were included. In the children with non-perforated appendicitis, no postoperative infectious complication occurred in 74 children during the first period versus two out of 153 (1%) during the second period. In cases of perforated appendicitis, postoperative infectious complications occurred two cases (10%) during the first period versus nine (11%) during the second. There were no significant differences between the two periods. CONCLUSION: In this population, antibiotic administration guidelines based on amoxicillin-clavulanic acid for stages I-III of appendicitis maintained a low rate of postoperative infectious complications and were not associated with a higher postoperative infectious complication rate than guidelines based on ticarcillin-clavulanic acid.
Asunto(s)
Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Profilaxis Antibiótica , Apendicectomía , Apendicitis/tratamiento farmacológico , Peritonitis/tratamiento farmacológico , Infección de la Herida Quirúrgica/prevención & control , Adolescente , Niño , Preescolar , Ácidos Clavulánicos/uso terapéutico , Femenino , Adhesión a Directriz , Humanos , Masculino , Estudios Retrospectivos , Ticarcilina/uso terapéuticoRESUMEN
Acute pulmonary exacerbations (APE) are well-described complications of cystic fibrosis (CF) and are associated with progressive morbidity and mortality. Despite aggressive management with two or more intravenous anti-pseudomonal agents, approximately 25% of exacerbations will result in a loss of lung function. The aim of this review is to provide an evidence-based summary of pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies utilizing anti-pseudomonal cephalosporins (i.e., ceftazidime and cefepime) and penicillins (i.e., piperacillin-tazobactam and ticarcillin-clavulanate) in the treatment of APE and to identify areas where further study is warranted. The ceftazidime and cefepime dosing ranges from the literature are 200-400 mg/kg/day divided every 6-8 hr, maximum 8-12 g/day, and 150-200 mg/kg/day divided every 6-8 hr, up to 6-8 g/day, respectively. The literature supported dosing ranges for piperacillin and ticarcillin are 350-600 mg/kg/day divided every 4 hr, maximum 18-24 g/day of piperacillin component, and 400-750 mg/kg/day divided every 6 hr, up to 24-30 g/day of ticarcillin component, respectively. As a large portion of CF patients will not regain their lung function following an APE, we suggest the need to optimize antibiotic dosing and dosing regimens used to treat an APE in efforts to improve outcomes for CF patients infected with Pseudomonas aeruginosa. Future studies are needed to determine the clinical efficacy of higher than FDA-approved doses of ceftazidime, cefepime, and ticarcillin-clavulanate in APE. The usefulness of high dose piperacillin (>600 mg/kg/day) may be limited due to treatment-related adverse effects. Further understanding of these adverse effects in CF patients is needed.
Asunto(s)
Antibacterianos/uso terapéutico , Cefalosporinas/uso terapéutico , Fibrosis Quística/complicaciones , Penicilinas/uso terapéutico , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa , Cefepima , Ceftazidima/uso terapéutico , Ácidos Clavulánicos/uso terapéutico , Progresión de la Enfermedad , Quimioterapia Combinada/métodos , Humanos , Pruebas de Sensibilidad Microbiana , Ácido Penicilánico/análogos & derivados , Ácido Penicilánico/uso terapéutico , Piperacilina/uso terapéutico , Combinación Piperacilina y Tazobactam , Infecciones por Pseudomonas/complicaciones , Ticarcilina/uso terapéutico , Resistencia betalactámicaRESUMEN
Topical compounded Timentin(®) diluted with an inactive vehicle has been reported to be effective in the treatment of otitis externa caused by Pseudomonas aeruginosa. The aims of this study were to determine the biological efficacy of Timentin(®) (ticarcillin and clavulanic acid) when diluted in the carrier vehicle Methopt(®) against P. aeruginosa and to determine the efficacy and stability of Timentin(®) aqueous stock concentrate solution. Timentin(®) stock concentrate was tested against four P. aeruginosa isolates on days 0, 7, 14, 21 and 28; then after 2, 3, 4, 5, 6, 9 and 12 months of storage at 4 or -20°C. The diluted Timentin(®)-Methopt(®) solutions were tested against all isolates after 0, 2, 4, 6, 8, 10, 12, 14, 17, 21, 24 and 28 days of storage at 24 or 4°C. Minimal inhibitory concentration (MIC) levels for all strains were determined using the broth microdilution method. The MIC of the stock solution remained relatively constant and acceptable throughout the study when stored at -20°C and was also acceptable for shorter time periods (6-9 months) when stored at 4°C. The MIC for the diluted Timentin(®)-Methopt(®) solution remained relatively constant and acceptable throughout the study for all four bacterial strains, with no difference between the solutions stored at 4 or 24°C. The results of this study indicate that storage of the Timentin(®) stock solution at -20°C does not compromise efficacy for at least 12 months and that Timentin(®) diluted in Methopt(®) was stable for 28 days when stored at either 4 or 24°C.
Asunto(s)
Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Pseudomonas aeruginosa/efectos de los fármacos , Administración Tópica , Animales , Química Farmacéutica , Ácidos Clavulánicos/administración & dosificación , Ácidos Clavulánicos/uso terapéutico , Almacenaje de Medicamentos , Pruebas de Sensibilidad Microbiana , Ticarcilina/administración & dosificación , Ticarcilina/uso terapéuticoRESUMEN
BACKGROUND: The Intermountain Cystic Fibrosis Pediatric Center utilizes ticarcillin-clavulanate 400 mg/kg/d divided every 6 hours, (maximum 24 g/d). This dosing strategy is higher than the Food and Drug Administration (FDA)-approved package labeling. We evaluated the microbiologic efficacy of this dosing regimen. OBJECTIVES: The primary study objective was to predict the pharmacokinetic (PK) and pharmacodynamic (PD) MIC breakpoints (the highest MIC with a probability of target attainment [PTA] of at least 90%) for the bacteriostatic and bactericidal targets of ticarcillin activity against Pseudomonas aeruginosa using the study dosing regimen. A secondary objective was to evaluate the tolerability profile of the higher ticarcillin-clavulanate dosing regimen in children with cystic fibrosis (CF). METHODS: This was a population-based PK-PD modeling study of pediatric CF patients admitted from January 1, 2005 to December 31, 2009 who received the dosing regimen for at least 7 days. Population PK and PD models were used to estimate PK and PD parameters for 127 clinically evaluable patients. A 10,000-patient Monte Carlo simulation was performed to estimate the target time in which free drug concentrations exceeded the MIC of the infecting organism. The 2 PK-PD targets of microbiologic efficacy included ≥30% for bacteriostasis and ≥50% for bactericidal effects of ticarcillin-clavulanate at higher than FDA-approved doses. RESULTS: A total of 127 patients (age, 0-19 years) met inclusion criteria. Serum concentration levels were modeled in this patient population using published PK parameters with intermittent ticarcillin peak concentrations reaching 288 (93.4) mg/L. The model predicted the PTA of the MICs for P. aeruginosa with a near-maximal bactericidal PK-PD MIC breakpoint of 16 µg/mL and a bacteriostasis PK-PD MIC breakpoint of 32 µg/mL. CONCLUSIONS: The results of our simulation suggest that in this select pediatric population, higher than FDA-approved doses of ticarcillin-clavulanate were effective in achieving bactericidal effects among pseudomonal isolates with MICs <16 µg/mL. Bacteriostatic and bactericidal effects were not frequently achieved among P. aeruginosa isolates with MICs >32 µg/mL. Additional studies are warranted to determine the clinical effectiveness of this dosing regimen.
Asunto(s)
Antibacterianos/administración & dosificación , Fibrosis Quística/tratamiento farmacológico , Adolescente , Antibacterianos/farmacocinética , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Área Bajo la Curva , Niño , Preescolar , Ácidos Clavulánicos/administración & dosificación , Ácidos Clavulánicos/farmacocinética , Ácidos Clavulánicos/farmacología , Ácidos Clavulánicos/uso terapéutico , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Humanos , Lactante , Recién Nacido , Pruebas de Sensibilidad Microbiana , Ticarcilina/administración & dosificación , Ticarcilina/farmacocinética , Ticarcilina/farmacología , Ticarcilina/uso terapéuticoRESUMEN
OBJECTIVE: To check the effectiveness of ticarcillin clavulanate versus cefepime as monotherapy in febrile neutropenia in lymphoma patients and also to check tolerability profile of both drugs. METHODS: We randomly assigned 107 neutropenic patients to receive either cefepime or ticarcillin/clavulanate. The clinical efficacy and tolerability profile of both drugs were compared using either cefepime or ticarcillin clavulanate (TC) as an empirical treatment for management of febrile neutropenia in lymphoma patients only with same characteristics at time of presentation. RESULTS: A significant difference in efficacy of the two treatment arms was noted. A successful outcome was reported with 28 (51%) out of 55 in cefepime arm compared to 16 (42%) out of 52 patients in ticarcillin/clavulanate group (p = 0.35; 95% Confidence). The distribution of time for defervesence was estimated for each treatment group and a trend to a shorter time for defervesence was found in the CEFEPIME group (48.4 hour for cefepime, 58.28 hour for TC group; p = 0.018). For microbiologically documented infections, the successful eradication rate was 49% (6 of 14 patients) for TC group as compared to 83% (10 of 12 patients) for cefepime group. This difference was statistically significant for microbiologically documented infections. Twenty seven (52%) patients of TC group and 19 (35%) of cefepime group required modifications of antibiotic regimen. The most frequent modifications consisted of the addition of either an amino glycoside (amikacin) or glycopeptides (vancomycin). CONCLUSION: CEFEPIME regimen was more effective than TC regimen, with a consistent trend toward a better outcome associated with cefepime compared to Ticarcillin/clavulanate.
Asunto(s)
Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Cefalosporinas/uso terapéutico , Ácido Clavulánico/uso terapéutico , Fiebre/tratamiento farmacológico , Neutropenia/tratamiento farmacológico , Ticarcilina/uso terapéutico , Adolescente , Adulto , Anciano , Antineoplásicos/efectos adversos , Infecciones Bacterianas/complicaciones , Cefepima , Niño , Preescolar , Quimioterapia Combinada , Femenino , Fiebre/etiología , Humanos , Lactante , Recién Nacido , Linfoma/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Neutropenia/etiología , Estudios Prospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVE: Earlier reports suggested that Pseudomonas aeruginosa frequent epidemic clones circulating in cystic fibrosis (CF) centres had increased virulence. However, recent data show no consistent associations with virulence, and suggest attenuation of virulence in chronic infection. Changes to infection control programmes in relation to frequent epidemic clones should be based on their frequency, virulence across all age groups and mode of acquisition. The Australian epidemic strain-1 (AES-1) (or the Melbourne epidemic strain) and AES-2 are common in CF clinics in mainland eastern Australia, but not in the environment. Both have shown increased virulence, but there are no data specifically in adults. This study examines the frequency and virulence of P. aeruginosa frequent epidemic clones in the adult CF clinic at Royal Prince Alfred Hospital, Sydney, Australia. METHODS: Two hundred and fifty-eight P. aeruginosa isolates from 112 participants were genotyped by pulsed field gel electrophoresis. Ninety-eight patients were followed up for 1 year and associations sought between infection with a frequent epidemic clone, clinical outcome and antibiotic resistance. RESULTS: Four frequent P. aeruginosa epidemic clones (AES-1, AES-2, S-1, S-2) affected almost 50% of participants. AES-1 predominated (38%). AES-1, AES-2 and S-1 were associated with increased exacerbations and hospital-admission days. AES-1 showed increased resistance to aminoglycosides and ticarcillin-clavulanate. CONCLUSIONS: This study supports the potential threat of frequent P. aeruginosa epidemic clones in adult CF populations.
Asunto(s)
Fibrosis Quística/epidemiología , Fibrosis Quística/microbiología , Infecciones por Pseudomonas/epidemiología , Pseudomonas aeruginosa/clasificación , Pseudomonas aeruginosa/patogenicidad , Adolescente , Adulto , Aminoglicósidos/uso terapéutico , Antibacterianos/uso terapéutico , Aspergillus fumigatus/aislamiento & purificación , Australia/epidemiología , Ácidos Clavulánicos/uso terapéutico , Células Clonales , Comorbilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/aislamiento & purificación , Estudios Retrospectivos , Esputo/microbiología , Stenotrophomonas maltophilia/aislamiento & purificación , Ticarcilina/uso terapéutico , Adulto JovenRESUMEN
OBJECTIVE: To present the technique for intra-articular catheter placement and report the clinical outcomes of 38 cases of equine synovial trauma and/or infection treated with broad-spectrum antimicrobials administered via an intrasynovial catheter (ISC). DESIGN: Retrospective study. PROCEDURE: Medical records of 38 horses treated for synovial trauma and sepsis with frequent antimicrobial administration through an ISC from 1995 to 2008 were reviewed. Follow-up information was obtained via clinical re-evaluation or telephone contact with the owners. RESULTS: The majority of horses (84%) received amikacin and Timentin(R) four times daily. In addition, synovial lavage through the ISC was carried out in 27 horses (71%). Only radiological evidence of osteolysis had a significant negative impact on both lameness at the time of hospital discharge and the long-term outcome. In total, 92% of horses treated with frequent antimicrobial administration through an ISC had clinical resolution of infection. Catheter obstruction occurred in three cases, necessitating replacement or removal, and two synovial fistulae developed at sites of open drainage. The majority of horses treated had a favourable outcome, with 86% being at least pasture sound and 43% returned to riding. CONCLUSION: Septic synovial structures treated with frequent antimicrobial administration through an ISC had a good prognosis for survival and 43% returned to riding, which is consistent with the results of other studies. The use of a simple ISC should be considered when broad-spectrum intrasynovial antimicrobial administration and lavage of a septic synovial structure are indicated.
Asunto(s)
Antibacterianos/administración & dosificación , Cateterismo/veterinaria , Enfermedades de los Caballos/tratamiento farmacológico , Sinovitis/veterinaria , Amicacina/administración & dosificación , Amicacina/uso terapéutico , Animales , Antibacterianos/uso terapéutico , Ácidos Clavulánicos/administración & dosificación , Ácidos Clavulánicos/uso terapéutico , Femenino , Caballos , Inyecciones Intraarticulares/veterinaria , Masculino , Pronóstico , Estudios Retrospectivos , Sinovitis/tratamiento farmacológico , Irrigación Terapéutica/veterinaria , Ticarcilina/administración & dosificación , Ticarcilina/uso terapéutico , Resultado del TratamientoRESUMEN
PURPOSE: To determine the characteristics of infectious keratitis related to plano cosmetic lenses. METHODS: Retrospective case study of a series of infectious keratitis among plano cosmetic lenses wearers. The main parameters were demographic data, medical history, risk factors for infectious complications and keratitis severity criteria, microbiological results, clinical course, and final visual acuity. RESULTS: Five patients were included, all females, ranging from 15 to 50 years of age. Four were emmetropic. One patient had undergone refractive photokeratectomy a few months before. All had risk factors for infectious complications. The fundamental causes of infections were diverse: bacterial abscesses, keratomycosis, and amoebic keratitis. All presented severity criteria. In two cases, the keratitis led to severe consequences with legal blindness requiring penetrating keratoplasty in one case. DISCUSSION: Infectious keratitis in plano cosmetic lenses wearers is not rare and may have dramatic consequences. Sales are specifically regulated and the lenses are considered cosmetic products, not medical devices. The sales regulations for plano cosmetic lenses should be updated, as several countries have already done after encountering many serious incidents.
Asunto(s)
Lentes de Contacto/efectos adversos , Queratitis/microbiología , Absceso/microbiología , Queratitis por Acanthamoeba/parasitología , Adolescente , Adulto , Antibacterianos/uso terapéutico , Antiinfecciosos/uso terapéutico , Antiinfecciosos Locales/uso terapéutico , Antifúngicos/uso terapéutico , Benzamidinas/uso terapéutico , Biguanidas/uso terapéutico , Ceguera/etiología , Opacidad de la Córnea/etiología , Cirugía Laser de Córnea , Femenino , Gentamicinas/uso terapéutico , Humanos , Persona de Mediana Edad , Infecciones por Pseudomonas/microbiología , Pirimidinas/uso terapéutico , Estudios Retrospectivos , Factores de Riesgo , Infecciones por Serratia/microbiología , Infecciones Estafilocócicas/microbiología , Ticarcilina/uso terapéutico , Triazoles/uso terapéutico , Vancomicina/uso terapéutico , Voriconazol , Adulto JovenRESUMEN
Septic arthritis in the elderly carries a high mortality. Underlying risk factors, such as diabetes, malignancy, chronic renal failure, rheumatoid arthritis, hepatobiliary disease and AIDS, should be assessed. Rare causative organisms are occasionally encountered. Here, we describe a case of an 80-year-old diabetic patient with liver cirrhosis who developed Klebsiella pneumoniae septic arthritis, which is a rare cause of joint infection. We postulate that this case supports the notion that the patient's knee effusion seeded during a primary K pneumoniae bacteraemia of intestinal origin and related to liver cirrhosis.
Asunto(s)
Artritis Infecciosa/diagnóstico , Infecciones por Klebsiella/diagnóstico , Articulación de la Rodilla/microbiología , Dolor Abdominal/etiología , Anciano de 80 o más Años , Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Antibacterianos/uso terapéutico , Artritis Infecciosa/complicaciones , Artritis Infecciosa/tratamiento farmacológico , Artritis Infecciosa/microbiología , Carcinoma Hepatocelular/complicaciones , Ácidos Clavulánicos/uso terapéutico , Resultado Fatal , Humanos , Infecciones por Klebsiella/complicaciones , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/complicaciones , Masculino , Ticarcilina/uso terapéuticoRESUMEN
The aim of cystic fibrosis (CF) care is to improve both the life expectancy and quality of life of patients. However, rising costs and limited resources of health services must be taken into account. There are many different antibiotic strategies for therapy of Pseudomonas aeruginosa infection in CF patients. In this 5-year retrospective study we found that the cost of treatment of initial infection is considerably lower than the cost of treating chronic P. aeruginosa infections. The percentage distribution of costs of antibiotic treatment in relationship to the administration route was considerably different between outpatients and inpatients. We observed an increase in antibiotic costs with the age of the patient and the decrease in FEV(1)values. The implementation of early eradication treatment, in addition to decreasing the prevalence of patients chronically infected by P. aeruginosa, might also bring about a notable decrease in costs.
Asunto(s)
Antibacterianos/economía , Costo de Enfermedad , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/economía , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/economía , Adulto , Antibacterianos/uso terapéutico , Ceftazidima/economía , Ceftazidima/uso terapéutico , Preescolar , Enfermedad Crónica , Ciprofloxacina/economía , Ciprofloxacina/uso terapéutico , Ácidos Clavulánicos/economía , Ácidos Clavulánicos/uso terapéutico , Colistina/economía , Colistina/uso terapéutico , Fibrosis Quística/complicaciones , Humanos , Meropenem , Infecciones por Pseudomonas/etiología , Pseudomonas aeruginosa , Estudios Retrospectivos , Tienamicinas/economía , Tienamicinas/uso terapéutico , Ticarcilina/economía , Ticarcilina/uso terapéutico , Tobramicina/economía , Tobramicina/uso terapéuticoRESUMEN
Ecthyma gangrenosum (EG) is a cutaneous manifestation of bacteremia and has classically been associated with Pseudomonas aeruginosa sepsis. The major risk factor for EG is neutropenia, and it is important to recognize that infectious lesions in neutropenic patients may lack the classic inflammatory features of infection in normal hosts. Ecthyma gangrenosum can be the herald of severe sepsis in neutropenic children.