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1.
Sci Rep ; 11(1): 21142, 2021 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-34707164

RESUMO

Limited data are available on antimicrobials exposure and microbiology evolution in pediatric acute myeloid leukemia (AML) patients underwent antimicrobials prophylaxis. To assess the effectiveness of antimicrobials prophylaxis, antibiotic susceptibilities of bacteria, and exposure of antimicrobials during intensive chemotherapy for AML patients, 90 consecutive de novo AML patients aged 0-18 years between January 1, 1997 and March 31, 2018 were enrolled. Vancomycin, ciprofloxacin and voriconazole prophylaxis was administered from January 1, 2010. During the preprophylaxis period, January 1997 to December 2009, 62 patients experienced a total of 87 episodes of bloodstream infection (BSI) and 17 episodes of invasive fungal infection (IFI) among 502 courses of chemotherapy. In contrast, 16 episodes of BSI occurred and no IFIs were reported to occur in 28 patients who received 247 courses of chemotherapy in the prophylaxis period. Patients who received antimicrobial prophylaxis had a significant reduction of BSI, IFI, and febrile neutropenia in comparison with patients without prophylaxis. Exposure to amikacin, carbapenem, amphotericin B was reduced in the prophylaxis period. Imipenem susceptibility of Enterobacter cloacae as well as vancomycin susceptibility of Enterococcus species were reduced in the prophylaxis period. At the time of the last follow up, patients with prophylaxis had a better subsequent 5-year overall survival rate than those without prophylaxis. Prophylactic antimicrobials administration in children with AML who undergo chemotherapy can significantly reduce the rates of life-threatening infection, exposure to antimicrobials, and might result in a better outcome.


Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Antifúngicos/uso terapêutico , Bacteriemia/prevenção & controle , Neutropenia Febril/prevenção & controle , Leucemia Mieloide Aguda/microbiologia , Micoses/prevenção & controle , Antibacterianos/administração & dosagem , Antifúngicos/administração & dosagem , Bacteriemia/tratamento farmacológico , Criança , Ciprofloxacina/administração & dosagem , Ciprofloxacina/uso terapêutico , Neutropenia Febril/tratamento farmacológico , Feminino , Humanos , Imipenem/administração & dosagem , Imipenem/uso terapêutico , Leucemia Mieloide Aguda/complicações , Masculino , Micoses/tratamento farmacológico , Vancomicina/administração & dosagem , Vancomicina/uso terapêutico , Voriconazol/administração & dosagem , Voriconazol/uso terapêutico
2.
Front Immunol ; 12: 684823, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122448

RESUMO

HI, a fusion protein that consists of the alpha-toxin (Hla) and the N2 domain of iron surface determinant B (IsdB), is one of the antigens in the previously reported S. aureus vaccine rFSAV and has already entered phase II clinical trials. Previous studies revealed that HI is highly immunogenic in both mice and healthy volunteers, and the humoral immune response plays key roles in HI-mediated protection. In this study, we further investigated the protective efficacy of immunization with HI plus four different adjuvants in a mouse bacteremia model. Results showed that HI-mediated protection was altered in response to different adjuvants. Using antisera from immunized mice, we identified seven B-cell immunodominant epitopes on Hla and IsdB, including 6 novel epitopes (Hla1-18, Hla84-101, Hla186-203, IsdB342-359, IsdB366-383, and IsdB384-401). The immunodominance of B-cell epitopes, total IgG titers and the levels of IFN-γ and IL-17A from mice immunized with HI plus different adjuvants were different from each other, which may explain the difference in protective immunity observed in each immunized group. Thus, our results indicate that adjuvants largely affected the immunodominance of epitopes and the protective efficacy of HI, which may guide further adjuvant screening for vaccine development and optimization.


Assuntos
Bacteriemia/imunologia , Toxinas Bacterianas/imunologia , Proteínas de Transporte de Cátions/imunologia , Epitopos de Linfócito B/imunologia , Proteínas Hemolisinas/imunologia , Epitopos Imunodominantes/imunologia , Infecções Estafilocócicas/prevenção & controle , Animais , Bacteriemia/prevenção & controle , Modelos Animais de Doenças , Feminino , Imunização Passiva , Imunoterapia Adotiva , Interferon gama/metabolismo , Interleucina-17/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Infecções Estafilocócicas/imunologia , Vacinas Antiestafilocócicas/administração & dosagem , Vacinas Antiestafilocócicas/imunologia
3.
JPEN J Parenter Enteral Nutr ; 44(1): 80-91, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31502272

RESUMO

BACKGROUND: To determine whether parenteral plus enteral glutamine supplementation influences microbial invasion in surgical infants who require parenteral nutrition (PN). METHODS: An prospective double-blind randomized controlled trial studying surgical infants receiving PN for at least 5 days for congenital or acquired intestinal anomalies (2009-2012) was used. Infants were randomized to receive either glutamine supplementation (parenteral plus enteral; total 400 mg/kg/d) or isonitrogenous control. The primary end point was microbial invasion evaluated after 5 days of supplementation and defined as: (i) positive conventional blood culture, (ii) evidence of microbial DNA in blood (polymerase chain reaction), (iii) plasma endotoxin level ≥50 pg/mL, or (iv) plasma level of lipopolysaccharide binding protein ≥50 ng/mL. Data are given as median (range) and compared by logistic regression. RESULTS: Sixty infants were randomized and reached the primary end point. Twenty-five patients had intestinal obstruction, 19 had abdominal wall defects, and 13 had necrotizing enterocolitis. Thirty-six infants showed evidence of microbial invasion during the study, and 17 of these were not detected by conventional blood culture. There was no significant difference between the 2 groups in the primary outcome; evidence of microbial invasion after 5 days was found in 9/31 (control group) and 8/29 (glutamine group) (odds ratio 0.83 [0.24-2.86; P = 0.77]). CONCLUSION: More than half of surgical infants requiring PN showed evidence of microbial invasion. Approximately half of this was not detectable by conventional blood cultures. Parenteral plus enteral glutamine supplementation had no effect on incidence of microbial invasion.


Assuntos
Bacteriemia/prevenção & controle , Procedimentos Cirúrgicos do Sistema Digestório , Glutamina/administração & dosagem , Nutrição Parenteral , Suplementos Nutricionais , Método Duplo-Cego , Nutrição Enteral , Humanos , Lactente , Recém-Nascido , Estudos Prospectivos
4.
JPEN J Parenter Enteral Nutr ; 44(4): 661-667, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31456260

RESUMO

BACKGROUND: The use of central venous catheter (CVC) access for home parenteral nutrition (HPN) is associated with catheter-related bloodstream infections (CRBSIs). There are limited data on the use of ethanol lock therapy (ELT) to prevent CRBSI in adult HPN patients. Our aim was to determine whether the routine institution of ELT decreased the incidence of CRBSI compared with historic controls at Emory University Hospital (EUH) in Atlanta, Georgia, USA. METHODS: EUH medical records of adult HPN patients discharged with a tunneled, silicone CVC on ELT were retrospectively studied during a pre-hoc determined 14-month observation period (n = 87; 13,386 catheter days) and compared with clinically similar HPN patients from the same institution before institution of the ELT protocol for all appropriate patients. The ELT protocol involved instilling 2 mL of 70% ethanol into each catheter lumen daily after the HPN cycle, following initial flushing with normal saline. RESULTS: Only 5 of 87 patients (5.7%) who received ELT were diagnosed with a CRBSI (0.45/1000 catheter days) during observation. We compared these data with our previously published clinically matched patient population from EUH (n = 22) receiving HPN via a silicone CVC without ELT. Of these historical controls, 45.5% were diagnosed with 1 or more CRBSIs (8.7/1000 catheter days) during observation (P < .001 vs the current ELT cohort). CONCLUSIONS: In this retrospective study with historical controls from the same academic center, institution of ELT in adults requiring HPN via a silicone CVC was associated with a marked (19-fold) reduction in CRBSI.


Assuntos
Bacteriemia , Infecções Relacionadas a Cateter , Etanol , Nutrição Parenteral no Domicílio , Adulto , Bacteriemia/epidemiologia , Bacteriemia/etiologia , Bacteriemia/prevenção & controle , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/prevenção & controle , Cateterismo Venoso Central , Cateteres Venosos Centrais/efeitos adversos , Feminino , Humanos , Masculino , Nutrição Parenteral no Domicílio/efeitos adversos , Estudos Retrospectivos , Centros de Atenção Terciária
5.
Infect Control Hosp Epidemiol ; 40(9): 1036-1045, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31230604

RESUMO

The proper functioning of central lines is imperative for the management of patients with cancer or on hemodialysis. However, these lifelines can become infected and can malfunction.Chelators such as citrate and EDTA have been widely studied alone or in combination with other antimicrobial agents in catheter lock solutions to prevent catheter-related bloodstream infections and to maintain catheter patency. Given their anticoagulation, antiplatelet aggregation, antibiofilm, antimicrobial activity, safety profile, as well as their low cost, chelators have long been considered alternatives to heparin and a vital component of catheter lock solutions. In this review, we present a detailed summary of the properties of chelators and in vitro and in vivo studies of chelator-containing lock solutions.


Assuntos
Anti-Infecciosos/uso terapêutico , Bacteriemia/prevenção & controle , Infecções Relacionadas a Cateter/prevenção & controle , Cateteres de Demora/microbiologia , Cateteres Venosos Centrais/microbiologia , Quelantes/uso terapêutico , Cateterismo Venoso Central , Humanos
6.
J Oncol Pharm Pract ; 25(4): 884-890, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30041584

RESUMO

BACKGROUND: Infection is the most common cause of morbidity and mortality in patients undergoing myleosuppressive therapy with the risk of infection being heightened during the neutropenic phase. Fluoroquinolones are most often utilized as prophylaxis, specifically levofloxacin or ciprofloxacin; however, there is increasing resistance among these agents. The objective of this study is to compare the efficacy of ciprofloxacin and levofloxacin when used prophylactically in hematopoietic stem cell transplantation patients. STUDY DESIGN: A retrospective cohort study conducted at a 443-bed tertiary teaching county hospital from 1 January 2005 to 31 September 2016. METHODS: Patients aged 18-89 who were admitted and received levofloxacin or ciprofloxacin post hematopoietic stem cell transplantation were evaluated. RESULTS: The patient population (N = 151) was predominantly male (93 vs. 58) and the median (IQR) age was 57 (20.1) years. There were 108 patients undergoing autologous hematopoietic stem cell transplantation compared to 43 undergoing allogenic hematopoietic stem cell transplantation. Significantly fewer patients who received levofloxacin (11/43, 25.6%) developed neutropenic fever compared to patients who received ciprofloxacin (61/108, 56.5%, p = 0.0006). Also there were significantly more positive blood cultures in the ciprofloxacin group (36/108, 33.3%) compared to the levofloxacin group (4/43, 9.3%); the majority of which were Gram-positive organisms (p = 0.0025). CONCLUSION: Prophylaxis with levofloxacin was associated with a lower incidence of febrile neutropenia and bacteremia when compared to ciprofloxacin in hematopoietic stem cell transplantation patients.


Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Ciprofloxacina/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Levofloxacino/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
7.
Clin Infect Dis ; 67(11): 1720-1728, 2018 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-29701766

RESUMO

Background: Bacteremia caused by extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is associated with inadequate empirical therapy and substantial mortality in neutropenic patients. Strategies are needed to identify neutropenic patients at high risk of these infections. Methods: From April 2014 to September 2016, we collected perianal swabs, both at admission and weekly thereafter, from patients undergoing hematopoietic stem cell transplantation (HSCT). Patients received prophylactic levofloxacin while neutropenic. Swabs were plated onto selective agar, colonies were identified and underwent antimicrobial susceptibility testing, and phenotypic ESBL testing and polymerase chain reaction for ß-lactamase genes were performed on ceftriaxone-resistant Enterobacteriaceae. We then determined the prevalence of pre-transplant ESBL-E colonization and risk of ESBL-E bacteremia. Colonizing and bloodstream isolates from patients with ESBL-E bacteremia underwent multilocus sequence typing and pulsed-field gel electrophoresis. Results: We analyzed 312 patients, including 212 allogeneic and 100 autologous HSCT recipients. Ten percent (31/312) of patients had pre-transplant ESBL-E colonization. Susceptibility rates of colonizing ESBL-E were: levofloxacin, 25%; cefepime, 9%; piperacillin-tazobactam, 84%; and meropenem, 97%. Of 31 patients colonized with ESBL-E pre-transplant, 10 (32%) developed ESBL-E bacteremia during their transplant admission, compared to 1 (0.4%) of 281 patients not colonized with ESBL-E (P < .001). All bloodstream ESBL-E were levofloxacin-resistant and colonizing and bloodstream isolates from individual patients had identical genotypic profiles. Conclusions: HSCT recipients who are colonized with levofloxacin-resistant ESBL-E pre-transplant and receive levofloxacin prophylaxis have high rates of bacteremia from their colonizing strain during neutropenia. Assessing for ESBL-E colonization in neutropenic patients could lead to optimization of empirical antibacterial therapy.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Enterobacteriaceae/complicações , Enterobacteriaceae/isolamento & purificação , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Levofloxacino/uso terapêutico , Neutropenia/complicações , Adulto , Idoso , Bacteriemia/complicações , Bacteriemia/prevenção & controle , Técnicas de Tipagem Bacteriana , Farmacorresistência Bacteriana , Eletroforese em Gel de Campo Pulsado , Enterobacteriaceae/enzimologia , Infecções por Enterobacteriaceae/prevenção & controle , Feminino , Trato Gastrointestinal/microbiologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Neutropenia/microbiologia , Estudos Prospectivos , Fatores de Risco , beta-Lactamases
8.
Clin Microbiol Infect ; 24(7): 749-754, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29208561

RESUMO

OBJECTIVES: We aimed to study whether ciprofloxacin prophylaxis reduces infectious complications in patients undergoing autologous haematopoietic cell transplantation (AHCT). METHODS: This is a quasi-experimental, retrospective, before-after study. We compared the incidence of bacterial-related complications among 356 patients with multiple myeloma (MM) (n = 202) and lymphoma (n = 154) who underwent AHCT with (n = 177) or without (n = 179) ciprofloxacin prophylaxis between 03/2007 and 10/2012 and between 10/2012 and 07/2016, respectively, at a single centre. RESULTS: Febrile neutropaenia, bacteraemia, and pneumonia were significantly more common among patients who underwent AHCT during the second study period and did not receive antibacterial prophylaxis compared with patients who underwent AHCT during the first study period and received antibacterial prophylaxis (89.9% (161/179) vs. 83.1% (147/177), difference 6.9%, 95% CI 0-14.1%, P = 0.002; 15.1% (27/179) vs. 4.5% (8/177), difference 10.6%, 95% CI 4.4-16.9%, p < 0.0001; 12.3% (22/179) vs. 6.2% (11/177), difference 6.1%, 95% CI 0-12.3%, p = 0.04, respectively). The number-needed-to-treat to prevent one episode of bacteraemia, pneumonia, and febrile neutropaenia was 8.6, 8.5, and 13.7, respectively. Patients with ciprofloxacin prophylaxis had higher rates of ciprofloxacin-resistant bacteraemia (62.5% (5/8) vs. 18.5% (5/27), difference 44%, 95% CI 7-70%, p = 0.01). In multivariate analysis, ciprofloxacin prophylaxis significantly decreased the odds of bacteraemia (OR 0.19, 95% CI 0.07-0.52; p < 0.0001) and pneumonia (OR 0.37, 95% CI 0.16-0.85, p = 0.02). CONCLUSION: According to our single-centre experience, patients with MM and lymphoma undergoing AHCT may benefit from antibacterial prophylaxis with ciprofloxacin.


Assuntos
Antibioticoprofilaxia , Ciprofloxacina/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Linfoma/cirurgia , Mieloma Múltiplo/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Transplante Autólogo/efeitos adversos , Adulto , Idoso , Antibacterianos/uso terapêutico , Bacteriemia/etiologia , Bacteriemia/microbiologia , Bacteriemia/prevenção & controle , Estudos Controlados Antes e Depois , Neutropenia Febril/etiologia , Neutropenia Febril/prevenção & controle , Feminino , Humanos , Israel , Masculino , Pessoa de Meia-Idade , Pneumonia/etiologia , Pneumonia/microbiologia , Pneumonia/prevenção & controle , Complicações Pós-Operatórias/microbiologia , Estudos Retrospectivos , Adulto Jovem
9.
J Antimicrob Chemother ; 73(1): 204-211, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29040595

RESUMO

BACKGROUND: There is demonstrated benefit with fluoroquinolones as infection prophylaxis in neutropenic patients; however, side effects, drug interactions and increasing resistance necessitate investigation of alternative therapies. OBJECTIVES: To compare the incidence of febrile neutropenia in high-risk patients with haematological malignancy receiving a fluoroquinolone with those receiving an oral third-generation cephalosporin (OTGC) as antibacterial prophylaxis during chemotherapy-induced neutropenia. METHODS: A retrospective, matched, single-centre study comparing clinical and microbiological outcomes in acute leukaemia patients receiving fluoroquinolones versus OTGCs as antibacterial prophylaxis after chemotherapy. RESULTS: A total of 120 patients (levofloxacin n = 80, OTGC n = 40) were included and matched. The 30 day incidence of febrile neutropenia was 89.7% (95% CI = 82.4-93.9). The rates of febrile neutropenia were similar between antimicrobials (OTGC versus levofloxacin HR = 0.90, 95% CI = 0.54-1.52, P = 0.70). The most frequent site of infection was the bloodstream (line related) (n = 24, 62%) and the majority (n = 28, 72%) of infections were caused by Gram-positive organisms. Groups were similar in terms of site of infection (P = 0.91) and morphology of recovered microorganisms (P = 0.74). There were significantly more cultures positive for Enterobacter spp. in the OTGC group (P = 0.043). Three patients died during follow-up (from first dose up to 30 days after the last dose) (30 day survival = 99.2%, 95% CI = 97.5-100), with only two of the reported deaths attributable to infection. CONCLUSIONS: These findings demonstrate comparable rates of febrile neutropenia and culture positivity with an increase in cultures positive for Enterobacter spp. when OTGCs are compared with levofloxacin for antibacterial prophylaxis during chemotherapy-induced neutropenia. Further prospective, randomized investigation is warranted.


Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Antineoplásicos/efeitos adversos , Cefalosporinas/uso terapêutico , Neutropenia Febril/induzido quimicamente , Neoplasias Hematológicas/tratamento farmacológico , Leucemia/tratamento farmacológico , Levofloxacino/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Bacteriemia/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
10.
World J Urol ; 36(3): 323-330, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29288398

RESUMO

PURPOSE: To systematically review and meta-analyse available evidence comparing fosfomycin trometamol (FT) to fluoroquinolone (FQ) prophylaxis to prevent transrectal ultrasound-guided prostate biopsy (TRUSPB) related infectious complications. METHODS: Electronic databases were queried for studies comparing FT to FQ-based TRUSPB prophylaxis. Studies were assessed for comparable outcomes and methodological quality (ROBINS-I modification). The primary outcome measure was the relative odds of overall infectious complications following TRUSPB according to FT/FQ treatment, which was evaluated with meta-analysis. Safety and tolerability were also assessed. The relative odds of infections of different severity [Grade 1, bacteriuria and afebrile urinary tract infection (UTI); Grade 2, bacteraemia, febrile UTI, and urosepsis] according to FT/FQ treatment were also estimated. RESULTS: Five studies, being three prospective randomised trials and two retrospective cohort studies, representing 3112 patients, were included. The relative odds of an infectious complication (OR 0.22, 95% CI 0.09-0.54) or of a more severe (Grade 2) infection (OR 0.13, 95% CI 0.07-0.26) were significantly lower in those receiving FT compared to FQ prophylaxis. A low incidence of medication-related side effects was observed. There were less observed infections due to FQ-resistant pathogens in those receiving FT prophylaxis. CONCLUSIONS: Patients who received FT prophylaxis were less likely than those who received FQ prophylaxis to develop infections overall, as well as severe and resistant infections after TRUSPB. Assessing the performance of FT in other geographic locations or in comparison to targeted prophylaxis based on risk assessment or rectal cultures is desired.


Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Bacteriemia/prevenção & controle , Ciprofloxacina/uso terapêutico , Fosfomicina/uso terapêutico , Levofloxacino/uso terapêutico , Próstata/patologia , Infecções Urinárias/prevenção & controle , Idoso , Biópsia com Agulha de Grande Calibre , Fluoroquinolonas/uso terapêutico , Humanos , Biópsia Guiada por Imagem , Masculino , Pessoa de Meia-Idade , Sepse/prevenção & controle , Ultrassonografia
11.
Ann Nutr Metab ; 71 Suppl 1: 31-36, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28950282

RESUMO

Major surgical procedures can alter intestinal microbiota and disrupt the intestinal barrier function, leaving the patient at risk for infection. Probiotics are defined as live microorganisms that confer a health benefit on the host when administered in adequate amounts. Although the efficacy of administering probiotics perioperatively to adults has been reported, the clinical significance of probiotics in children undergoing surgery is still unclear. This study provides a brief overview of our randomized controlled trial of preoperative probiotic administration to children, and discusses the relationship between probiotics and their effects in the perioperative period, particularly focusing on bacteremia.


Assuntos
Bacteriemia/prevenção & controle , Bifidobacterium , Complicações Pós-Operatórias/prevenção & controle , Probióticos/uso terapêutico , Bacteriemia/epidemiologia , Criança , Suplementos Nutricionais , Humanos , Incidência , Cuidados Pré-Operatórios , Probióticos/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Infect Immun ; 85(11)2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28808157

RESUMO

Pulmonary infection by Streptococcus pneumoniae is characterized by a robust alveolar infiltration of neutrophils (polymorphonuclear cells [PMNs]) that can promote systemic spread of the infection if not resolved. We previously showed that 12-lipoxygenase (12-LOX), which is required to generate the PMN chemoattractant hepoxilin A3 (HXA3) from arachidonic acid (AA), promotes acute pulmonary inflammation and systemic infection after lung challenge with S. pneumoniae As phospholipase A2 (PLA2) promotes the release of AA, we investigated the role of PLA2 in local and systemic disease during S. pneumoniae infection. The group IVA cytosolic isoform of PLA2 (cPLA2α) was activated upon S. pneumoniae infection of cultured lung epithelial cells and was critical for AA release from membrane phospholipids. Pharmacological inhibition of this enzyme blocked S. pneumoniae-induced PMN transepithelial migration in vitro Genetic ablation of the cPLA2 isoform cPLA2α dramatically reduced lung inflammation in mice upon high-dose pulmonary challenge with S. pneumoniae The cPLA2α-deficient mice also suffered no bacteremia and survived a pulmonary challenge that was lethal to wild-type mice. Our data suggest that cPLA2α plays a crucial role in eliciting pulmonary inflammation during pneumococcal infection and is required for lethal systemic infection following S. pneumoniae lung challenge.


Assuntos
Células Epiteliais/imunologia , Fosfolipases A2 do Grupo IV/imunologia , Interações Hospedeiro-Patógeno , Pulmão/imunologia , Infecções Pneumocócicas/imunologia , Pneumonia Bacteriana/imunologia , Animais , Ácido Araquidônico/imunologia , Ácido Araquidônico/metabolismo , Bacteriemia/genética , Bacteriemia/imunologia , Bacteriemia/prevenção & controle , Linhagem Celular Tumoral , Fatores Quimiotáticos/imunologia , Fatores Quimiotáticos/metabolismo , Clorobenzoatos/farmacologia , Cinamatos/farmacologia , Cicloexanonas/farmacologia , Inibidores Enzimáticos/farmacologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/enzimologia , Células Epiteliais/microbiologia , Fosfolipases A2 do Grupo IV/antagonistas & inibidores , Fosfolipases A2 do Grupo IV/deficiência , Fosfolipases A2 do Grupo IV/genética , Humanos , Pulmão/efeitos dos fármacos , Pulmão/enzimologia , Pulmão/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Infiltração de Neutrófilos/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Neutrófilos/microbiologia , Infecções Pneumocócicas/genética , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/mortalidade , Pneumonia Bacteriana/genética , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/mortalidade , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/patogenicidade , Análise de Sobrevida , Migração Transendotelial e Transepitelial/efeitos dos fármacos , Migração Transendotelial e Transepitelial/imunologia , ortoaminobenzoatos/farmacologia
13.
J Vasc Access ; 18(Suppl. 1): 34-38, 2017 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-28297055

RESUMO

The prevention of catheter-related blood stream infections (CRBSI) in hemodialysis (HD) patients remains a challenge because of high morbidity and mortality associated to CRBSI. Alternative locking solutions (ALS) containing an antithrombotic substance with additional antimicrobial or antibiofilm properties (citrate, ethylenediaminetetraacetic acid [EDTA], 70% ethanol, thrombolytics) with or without the addition of molecules with specific antimicrobial activity (antibiotics, taurolidine, paraben-methylene-blue) has been proposed with the aim to prevent or eradicate intraluminal biofilm colonization and subsequent CRBSI. In this review, we examine the available evidence concerning their efficacy and potential side effects, in order to determine whether ALS should be implemented widely or only in selected cases.


Assuntos
Anti-Infecciosos/uso terapêutico , Bacteriemia/prevenção & controle , Infecções Relacionadas a Cateter/prevenção & controle , Cateterismo Venoso Central/instrumentação , Cateteres de Demora , Cateteres Venosos Centrais , Diálise Renal , Anti-Infecciosos/efeitos adversos , Anticoagulantes/uso terapêutico , Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Biofilmes , Infecções Relacionadas a Cateter/diagnóstico , Infecções Relacionadas a Cateter/microbiologia , Cateterismo Venoso Central/efeitos adversos , Cateteres de Demora/efeitos adversos , Cateteres de Demora/microbiologia , Cateteres Venosos Centrais/efeitos adversos , Cateteres Venosos Centrais/microbiologia , Desenho de Equipamento , Humanos , Fatores de Risco , Resultado do Tratamento
14.
J Pediatr Hematol Oncol ; 39(3): e131-e135, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28234737

RESUMO

BACKGROUND: The aim of the study was to describe the incidence and type of bacterial infections associated with the use of ciprofloxacin prophylaxis as single agent in pediatric patients with acute myeloid leukemia (AML). PROCEDURE: This was a retrospective review of all patients with AML, who were treated according to the AML02 protocol between 2011 and 2015. The medical records were reviewed for any positive cultures from the initiation of the protocol until death or protocol discontinuation. Patient demographics, type of infections, type of isolated bacteria, and intensive care unit admissions were recorded. RESULTS: A total of 50 patients were evaluated, who were of a mean age of 8 years±5.1 (SD). We identified 77 episodes of bacterial infections in 42 (84%) patients. Among those bacterial infections, 73 episodes were with bacteremia and included 45 (62%) gram-positive bacterial infections, 24 (33%) gram-negative bacterial infections, and 4 (6%) mixed gram-negative and gram-positive bacterial infections. Coagulase-negative Staphylococcus and Viridans streptococci were the most commonly isolated bacteria in 33% and 30% of the episodes, respectively. Seventeen (45%) patients with bacteremia required intensive care unit admission. CONCLUSIONS: A high rate of bacterial infection was detected in patients who received the AML02 protocol, mainly gram-positive bacterial infections. The prophylactic regimen should be reconsidered for its efficacy, and other antibacterial prophylaxis may be used.


Assuntos
Antibioticoprofilaxia/métodos , Infecções Bacterianas/prevenção & controle , Ciprofloxacina/uso terapêutico , Leucemia Mieloide Aguda/complicações , Adolescente , Antibacterianos/uso terapêutico , Bacteriemia/prevenção & controle , Criança , Pré-Escolar , Feminino , Infecções por Bactérias Gram-Negativas/prevenção & controle , Infecções por Bactérias Gram-Positivas/prevenção & controle , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Estudos Retrospectivos , Falha de Tratamento
15.
JPEN J Parenter Enteral Nutr ; 41(6): 1072-1074, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-26297019

RESUMO

We report the use of ethanol lock therapy to dramatically reduce the incidence of catheter-related bloodstream infections (CRBSIs) in a long-term adult home parenteral nutrition (HPN) patient. This case study demonstrates the efficacy of ethanol lock therapy in eliminating CRBSIs when other treatments have been unsuccessful. We suggest that ethanol lock therapy has an important role in decreasing CRBSI in HPN patients with recurrent CRBSIs.


Assuntos
Bacteriemia/prevenção & controle , Infecções Relacionadas a Cateter/prevenção & controle , Nutrição Parenteral no Domicílio/efeitos adversos , Antibacterianos/uso terapêutico , Cateteres de Demora/efeitos adversos , Cateteres de Demora/microbiologia , Etanol/uso terapêutico , Feminino , Humanos , Incidência , Pessoa de Meia-Idade
16.
Pediatr Infect Dis J ; 36(2): 233-235, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27846059

RESUMO

To reduce the incidence of catheter-related bloodstream infections in home parenteral nutrition patients, the use of taurolidine was introduced in the Sophia Children's Hospital in 2011. This introduction led to a reduction in catheter-related bloodstream infections: 12.7/1000 catheter days before the use of taurolidine, compared with 4.3/1000 catheter days afterwards (n = 7) [relative risk = 0.36, 95% confidence interval: 0.20-0.65 (P = 0.018)].


Assuntos
Anti-Infecciosos/uso terapêutico , Bacteriemia , Infecções Relacionadas a Cateter , Nutrição Parenteral no Domicílio/estatística & dados numéricos , Taurina/análogos & derivados , Tiadiazinas/uso terapêutico , Anti-Infecciosos/administração & dosagem , Bacteriemia/tratamento farmacológico , Bacteriemia/epidemiologia , Bacteriemia/prevenção & controle , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/prevenção & controle , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Nutrição Parenteral no Domicílio/efeitos adversos , Nutrição Parenteral no Domicílio/métodos , Estudos Retrospectivos , Taurina/administração & dosagem , Taurina/uso terapêutico , Tiadiazinas/administração & dosagem
17.
Microb Pathog ; 102: 143-147, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27914960

RESUMO

The aim of present work was to investigate preventive role of orally administered Aloe vera supplemented probiotic lassi (APL) on Shigella dysenteriae infection in mice. At the end of experimental period (2, 5 and 7 days of challenging), different organs such as spleen, liver, small intestine, large intestine, and peritoneal fluid were collected and assessed for Shigella colonization. Secretary IgA was estimated in intestinal fluid. Blood was collected in heparinized tubes for various haematological studies. Oral administration of APL showed a significant (p < 0.05) reduction in the Shigella counts (log cfu/mL) in all organs as compared to other treatment groups at different intervals after post feeding. Similarly, secretary IgA antibody levels (µg/mL) in intestinal fluid were significantly (p < 0.05) increased in case of APL fed mice. Further, feeding of APL also demonstrated a positive effect on different haematological parameters viz. Hb (gm %), RBC and WBC count. The results indicated the immunoprotective effects of APL against Shigella dysenteriae induced infection in mice.


Assuntos
Aloe , Antibiose , Bacteriemia/microbiologia , Suplementos Nutricionais , Disenteria Bacilar/microbiologia , Mucosa Intestinal/microbiologia , Probióticos , Shigella/patogenicidade , Aloe/química , Animais , Bacteriemia/tratamento farmacológico , Bacteriemia/imunologia , Bacteriemia/prevenção & controle , Carga Bacteriana , Modelos Animais de Doenças , Disenteria Bacilar/dietoterapia , Disenteria Bacilar/imunologia , Imunoglobulina A Secretora/imunologia , Mucosa Intestinal/imunologia , Camundongos , Extratos Vegetais/imunologia
18.
Pediatr Surg Int ; 32(9): 863-7, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27461433

RESUMO

PURPOSE: Children with intestinal failure (IF) requiring central venous catheters (CVCs) often experience frequent catheter-related bloodstream infections (CRBSIs), which is a serious and life-threatening complication. To reduce the incidence of CRBSI, prophylactic ethanol lock therapy (ELT) was initiated. METHODS: Patients with IF received home parenteral nutrition via a silicone tunneled CVC. All of them had received therapeutic ELT from January 2009 (first period) and prophylactic ELT from December 2012 (second period). Prophylactic ELT refers to ethanol lock for 2 h during the monthly hospital visit. We compared the CRBSI rate and number of CVC replacements between both periods. RESULTS: Four patients received 19 CVCs for a total of 5623 catheter days. In the first period, there were 12 CRBSIs in 1823 catheter days (rate 6.77 per 1000 catheter days). In the second period, there were 9 CRBSIs in 3800 catheter days (rate 3.13 per 1000 catheter days). Overall, the rate of CVC replacement decreased from 4.92 to 1.72 per 1000 catheter days (p = 0.04). No adverse reactions were experienced during ethanol instillation. CONCLUSION: Monthly prophylactic ELT for IF patients is considered to be a safe and effective modality for reducing the replacement of CVCs due to CRBSIs.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Bacteriemia/prevenção & controle , Infecções Relacionadas a Cateter/prevenção & controle , Etanol/administração & dosagem , Nutrição Parenteral no Domicílio , Cateterismo/estatística & dados numéricos , Cateteres de Demora , Cateteres Venosos Centrais , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino
19.
Infect Dis (Lond) ; 48(6): 443-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27030917

RESUMO

BACKGROUND: Due to an outbreak of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae, the routine use of fluoroquinolone prophylaxis was questioned. As a result, this study was conducted with the aim to evaluate the impact of ciprofloxacin-prophylaxis on the use of broad-spectrum antibioctics and anti-mycotics. METHODS: A cohort of 139 consecutive patients with acute leukaemia treated with remission-inducing induction chemotherapy between 2004-2012 at the Department of Haematology in Uppsala University Hospital was analysed. RESULTS: Fifty-three patients (38%) received broad-spectrum antibiotics at the initiation of chemotherapy and were not eligible for prophylaxis. Of the remaining patients, the initiation of broad-spectrum antibiotics was delayed by 3 days in those receiving ciprofloxacin prophylaxis (n = 47) compared with those receiving no prophylaxis (n = 39). The median duration of systemic antibiotic treatment was 6 days shorter in patients receiving ciprofloxacin prophylaxis (12 vs 18 days; p = 0.0005) and the cumulative (total) median days on systemic antibiotic treatment was shortened by 8 days (15 vs 23 days, p = 0.0008). Piperacillin/tazobactam (p = 0.02), carbapenems (p = 0.05) and empiric broad-spectrum antifungals (p < 0.01) were used significantly less often when ciprofloxacin prophylaxis was given. CONCLUSIONS: Ciprofloxacin prophylaxis delayed empiric therapy by 3 days and reduced overall antibiotic use in this study. These benefits must be evaluated vs the risks of development of resistant bacterial strains, making fluoroquinolone prophylaxis an open question for debate.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/prevenção & controle , Ciprofloxacina/uso terapêutico , Leucemia/tratamento farmacológico , Leucemia/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/sangue , Bacteriemia/microbiologia , Bacteriemia/prevenção & controle , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Carbapenêmicos/uso terapêutico , Estudos de Coortes , Neutropenia Febril/microbiologia , Neutropenia Febril/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Micoses/tratamento farmacológico , Micoses/microbiologia , Micoses/prevenção & controle
20.
Antimicrob Agents Chemother ; 60(6): 3426-32, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27001822

RESUMO

In cancer patients with long-term central venous catheters (CVC), removal and reinsertion of a new CVC at a different site might be difficult because of the unavailability of accessible vascular sites. In vitro and animal studies showed that a minocycline-EDTA-ethanol (M-EDTA-EtOH) lock solution may eradicate microbial organisms in biofilms, hence enabling the treatment of central line-associated bloodstream infections (CLABSI) while retaining the catheter in situ Between April 2013 and July 2014, we enrolled 30 patients with CLABSI in a prospective study and compared them to a historical group of 60 patients with CLABSI who had their CVC removed and a new CVC inserted. Each catheter lumen was locked with an M-EDTA-EtOH solution for 2 h administered once daily, for a total of 7 doses. Patients who received locks had clinical characteristics that were comparable to those of the control group. The times to fever resolution and microbiological eradication were similar in the two groups. Patients with the lock intervention received a shorter duration of systemic antibiotic therapy than that of the control patients (median, 11 days versus 16 days, respectively; P < 0.0001), and they were able to retain their CVCs for a median of 74 days after the onset of bacteremia. The M-EDTA-EtOH lock was associated with a significantly decreased rate of mechanical and infectious complications compared to that of the CVC removal/reinsertion group, who received a longer duration of systemic antimicrobial therapy. (This study has been registered at ClinicalTrials.gov under registration no. NCT01539343.).


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Infecções Relacionadas a Cateter/tratamento farmacológico , Cateterismo Venoso Central/efeitos adversos , Cateteres Venosos Centrais/microbiologia , Ácido Edético/uso terapêutico , Etanol/uso terapêutico , Minociclina/uso terapêutico , Adulto , Idoso , Bacteriemia/prevenção & controle , Biofilmes/efeitos dos fármacos , Infecções Relacionadas a Cateter/prevenção & controle , Cateteres Venosos Centrais/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Projetos Piloto , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
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