RESUMO
BACKGROUND: Diagnosis of invasive candidiasis (IC) relies on insensitive cultures; the relative utility of fungal biomarkers in children is unclear. METHODS: This multinational observational cohort study enrolled patients aged >120 days and <18 years with concern for IC from 1 January 2015 to 26 September 2019 at 25 centers. Blood collected at onset of symptoms was tested using T2Candida, Fungitell (1â3)-ß-D-glucan, Platelia Candida Antigen (Ag) Plus, and Platelia Candida Antibody (Ab) Plus assays. Operating characteristics were determined for each biomarker, and assays meeting a defined threshold considered in combination. Sterile site cultures were the reference standard. RESULTS: Five hundred participants were enrolled at 22 centers in 3 countries, and IC was diagnosed in 13 (2.6%). Thirteen additional blood specimens were collected and successfully spiked with Candida species, to achieve a 5.0% event rate. Valid T2Candida, Fungitell, Platelia Candida Ag Plus, and Platelia Candida Ab Plus assay results were available for 438, 467, 473, and 473 specimens, respectively. Operating characteristics for T2Candida were most optimal for detecting IC due to any Candida species, with results as follows: sensitivity, 80.0% (95% confidence interval, 59.3%-93.2%), specificity 97.1% (95.0%-98.5%), positive predictive value, 62.5% (43.7%-78.9%), and negative predictive value, 98.8% (97.2%-99.6%). Only T2Candida and Platelia Candida Ag Plus assays met the threshold for combination testing. Positive result for either yielded the following results: sensitivity, 86.4% (95% confidence interval, 65.1%- 97.1%); specificity, 94.7% (92.0%-96.7%); positive predictive value, 47.5% (31.5%-63.9%); and negative predictive value, 99.2% (97.7%-99.8%). CONCLUSIONS: T2Candida alone or in combination with Platelia Candida Ag Plus may be beneficial for rapid detection of Candida species in children with concern for IC. CLINICAL TRIALS REGISTRATION: NCT02220790.
Assuntos
Candidíase Invasiva , Adolescente , Antígenos de Fungos , Biomarcadores , Candida , Candidíase , Candidíase Invasiva/diagnóstico , Criança , Humanos , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
Hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients are at increased risk for Clostridioides difficile infection (CDI). We conducted a multicenter retrospective study to describe the incidence of CDI in children transplanted between January 2010 and June 2013. Nested case-control substudies, matched 1:1 by transplant type, institution, patient age, and time of year (quartile) of transplant, identified CDI risk factors. Cohorts included 1496 HCT and 1090 SOT recipients. Among HCT recipients, 355 CDI episodes were diagnosed in 265 recipients (18.2%). Nested case-control study identified prior history of CDI (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.5-4.7), proton pump inhibitors (PPIs; OR 2.1, 95% CI 1.3-3.4), and exposure to third- (OR 2.4, 95% CI 1.4-4.2) or fourth-generation (OR 2.1, 95% CI 1.2-3.7) cephalosporins as risk factors. Notably, fluoroquinolone exposure appeared protective (OR 0.6, 95% CI 0.3-0.9). Ninety-two episodes of CDI were diagnosed among 79 SOT recipients (7.3%), and exposure to PPIs (OR 2.4, 95% CI 1.1-5.4) and third-generation cephalosporin therapy (OR 3.9, 95% CI 1.4-10.5) were identified as risk factors. Strategies to decrease PPI use and changes in the class of prophylactic antibiotics may impact CDI incidence and warrant further study.
Assuntos
Clostridioides difficile , Infecções por Clostridium , Transplante de Células-Tronco Hematopoéticas , Transplante de Órgãos , Antibacterianos/uso terapêutico , Estudos de Casos e Controles , Criança , Clostridioides , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Transplante de Órgãos/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , TransplantadosRESUMO
We describe the first reported pediatric patient to our knowledge with a spindle cell pseudotumor caused by Mycobacterium genavense in a hematopoietic stem cell transplant recipient, and review the literature of such an entity in the transplant population.
Assuntos
Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Histiócitos/microbiologia , Imunossupressores/efeitos adversos , Linfonodos/microbiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas/patogenicidade , Condicionamento Pré-Transplante/efeitos adversos , Abdome , Adolescente , Alemtuzumab , Antibioticoprofilaxia , Antibióticos Antituberculose/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Transplante de Medula Óssea/efeitos adversos , Líquido da Lavagem Broncoalveolar/microbiologia , Ciclosporina/efeitos adversos , Ciclosporina/uso terapêutico , Diabetes Mellitus Tipo 1/congênito , Diabetes Mellitus Tipo 1/cirurgia , Diarreia/cirurgia , Doenças Genéticas Ligadas ao Cromossomo X/cirurgia , Rejeição de Enxerto/cirurgia , Humanos , Doenças do Sistema Imunitário/congênito , Doenças do Sistema Imunitário/cirurgia , Imunossupressores/uso terapêutico , Linfonodos/patologia , Masculino , Melfalan/efeitos adversos , Melfalan/uso terapêutico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/patologia , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/uso terapêutico , Micobactérias não Tuberculosas/isolamento & purificação , Fotoferese , Reação em Cadeia da Polimerase , Condicionamento Pré-Transplante/métodos , Vidarabina/efeitos adversos , Vidarabina/análogos & derivados , Vidarabina/uso terapêuticoRESUMO
BACKGROUND: Adjunctive diagnostic studies (aDS) are recommended to identify occult dissemination in patients with candidemia. Patterns of evaluation with aDS across pediatric settings are unknown. METHODS: Candidemia episodes were included in a secondary analysis of a multicenter comparative effectiveness study that prospectively enrolled participants age 120 days to 17 years with invasive candidiasis (predominantly candidemia) from 2014 to 2017. Ophthalmologic examination (OE), abdominal imaging (AbdImg), echocardiogram, neuroimaging, and lumbar puncture (LP) were performed per clinician discretion. Adjunctive diagnostic studies performance and positive results were determined per episode, within 30 days from candidemia onset. Associations of aDS performance with episode characteristics were evaluated via mixed-effects logistic regression. RESULTS: In 662 pediatric candidemia episodes, 490 (74%) underwent AbdImg, 450 (68%) OE, 426 (64%) echocardiogram, 160 (24%) neuroimaging, and 76 (11%) LP; performance of each aDS per episode varied across sites up to 16-fold. Longer durations of candidemia were associated with undergoing OE, AbdImg, and echocardiogram. Immunocompromised status (58% of episodes) was associated with undergoing AbdImg (adjusted odds ratio [aOR] 2.38; 95% confidence intervals [95% CI] 1.51-3.74). Intensive care at candidemia onset (30% of episodes) was associated with undergoing echocardiogram (aOR 2.42; 95% CI 1.51-3.88). Among evaluated episodes, positive OE was reported in 15 (3%), AbdImg in 30 (6%), echocardiogram in 14 (3%), neuroimaging in 9 (6%), and LP in 3 (4%). CONCLUSIONS: Our findings show heterogeneity in practice, with some clinicians performing aDS selectively, potentially influenced by clinical factors. The low frequency of positive results suggests that targeted application of aDS is warranted.
Assuntos
Candidemia , Candidíase Invasiva , Humanos , Criança , Idoso de 80 Anos ou mais , Candidemia/diagnóstico , Candidemia/microbiologia , Candidíase Invasiva/tratamento farmacológico , Modelos Logísticos , Estudos de Coortes , Fatores de Risco , Antifúngicos/uso terapêuticoRESUMO
This study intends to describe for the first time a cohort of Mexican patients with Costello syndrome. The five exons of the HRAS gene were amplified in DNA samples from 13 patients with a clinical suspicion of Costello syndrome. PCR products were sequenced using the Ready Reaction Big Dye Terminator v.3.0 Kit and an ABI PRISM 310 sequencer. Only five patients (38%) showed causal variant in codon 12 of the HRAS gene (four with the p.Gly12Ser and one with the p.Gly12Ala variant). Three patients showed silent polymorphic variants (p.His27His and p.Leu159Leu). Clinical features in patients carrying the causal variant were variable. The alternative diagnosis of cardio-facio-cutaneous syndrome was considered in patients who did not have a causative variant in HRAS.
Assuntos
Síndrome de Costello , Displasia Ectodérmica , Proteínas Proto-Oncogênicas p21(ras) , Síndrome de Costello/diagnóstico , Síndrome de Costello/genética , Fácies , Insuficiência de Crescimento , Humanos , México , Fenótipo , Proteínas Proto-Oncogênicas p21(ras)/genéticaRESUMO
E-consults replace "curbside" interactions, facilitate provider-specialist communication, document within the medical record, and track relative value units (RVUs). Pediatric infectious diseases (PID) E-consults commonly relate to vaccines, exposures, diagnoses, and treatments. The documented RVU effort of 197 consecutive PID E-consults was equivalent to 70 level 4 new outpatient consults.
Assuntos
Doenças Transmissíveis , Médicos , Consulta Remota , Criança , Doenças Transmissíveis/diagnóstico , Humanos , Infectologia , EspecializaçãoRESUMO
BACKGROUND: Invasive candidiasis is the most common invasive fungal disease in children and adolescents, but there are limited pediatric-specific antifungal effectiveness data. We compared the effectiveness of echinocandins to triazoles or amphotericin B formulations (triazole/amphotericin B) as initial directed therapy for invasive candidiasis. METHODS: This multinational observational cohort study enrolled patients aged >120 days and <18 years with proven invasive candidiasis from January 1, 2014, to November 28, 2017, at 43 International Pediatric Fungal Network sites. Primary exposure was initial directed therapy administered at the time qualifying culture became positive for yeast. Exposure groups were categorized by receipt of an echinocandin vs receipt of triazole/amphotericin B. Primary outcome was global response at 14 days following invasive candidiasis onset, adjudicated by a centralized data review committee. Stratified Mantel-Haenszel analyses estimated risk difference between exposure groups. RESULTS: Seven-hundred and fifty invasive candidiasis episodes were identified. After exclusions, 541 participants (235 in the echinocandin group and 306 in the triazole/amphotericin B group) remained. Crude failure rates at 14 days for echinocandin and triazole/amphotericin B groups were 9.8% (95% confidence intervals [CI]: 6.0% to 13.6%) and 13.1% (95% CI: 9.3% to 16.8%), respectively. The adjusted 14-day risk difference between echinocandin and triazole/amphotericin B groups was -7.1% points (95% CI: -13.1% to -2.4%), favoring echinocandins. The risk difference was -0.4% (95% CI: -7.5% to 6.7%) at 30 days. CONCLUSIONS: In children with invasive candidiasis, initial directed therapy with an echinocandin was associated with reduced failure rate at 14 days but not 30 days. These results may support echinocandins as initial directed therapy for invasive candidiasis in children and adolescents. CLINICAL TRIALS REGISTRATION: NCT01869829.
RESUMO
Two infants treated for syphilis born to at risk mothers who screened negative at their first prenatal visit but were not rescreened at delivery are described. The first presented with classic, but unrecognized, features of congenital syphilis. In the second case, possible early maternal syphilis was diagnosed soon after delivery using the treponemal first reverse-screening algorithm. Although the child's physical exam was normal and the maternal rapid plasma reagin (RPR) negative, the child was treated for syphilis because maternal confirmatory treponemal tests suggested recent seroconversion. Given the re-emergence of congenital syphilis, our report aims to demonstrate the importance of rescreening women at increased risk and improve awareness of common manifestations of the syphilis disease in the newborn. For women at increased risk, repeat syphilis testing early in the third trimester and again at delivery in communities and populations with a high prevalence of syphilis is recommended.
RESUMO
We report a significantly higher occurrence of adverse events associated with prolonged courses of piperacillin-tazobactam compared with other antibacterial agents used for pediatric outpatient parenteral antimicrobial therapy. These adverse events were characterized by a constellation of clinical findings including fever, hematologic abnormalities and transaminitis. Adverse events related to piperacillin-tazobactam should be considered in patients who develop a febrile illness associated with a prolonged course of therapy.
Assuntos
Antibacterianos/efeitos adversos , Infusões Parenterais/estatística & dados numéricos , Ácido Penicilânico/análogos & derivados , Adolescente , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Pacientes Ambulatoriais/estatística & dados numéricos , Ácido Penicilânico/administração & dosagem , Ácido Penicilânico/efeitos adversos , Ácido Penicilânico/uso terapêutico , Piperacilina/administração & dosagem , Piperacilina/efeitos adversos , Piperacilina/uso terapêutico , Combinação Piperacilina e TazobactamRESUMO
BACKGROUND: During the Fall of 2014, numerous children were hospitalized with asthma or respiratory distress related to Enterovirus D68 (EV-D68). A large proportion initially tested positive for rhinovirus. During this period our laboratory noted a cross-reactivity between EV-D68 and the rhinovirus component of the GenMark multiplex respiratory viral panel. Many other laboratories used assays not designed to distinguish these Picornoviridae. METHODS: To compare the presentation and outcomes of patients with rhinovirus and EV-D68, 103 GenMark rhinovirus positive nasopharyngeal swabs from hospitalized children were retested for EV-D68. RESULTS: EV-D68 positive patients versus EV-D68 negative patients were more likely to have a history of asthma (33.3% vs. 11.0%, P = 0.02) and to present with acute respiratory illness (66.7% vs. 40.2%, P = 0.048), especially status asthmaticus (47.6% vs. 2.4%, P < 0.001). On admission they had more wheezing, respiratory distress, and lower respiratory tract involvement, and were more likely to be treated with steroids and discharged home on asthma medications. Respiratory viral coinfection was less common in EV-D68 positive vs EV-D68 negative patients. In patients without a respiratory viral coinfection the overall findings were similar. CONCLUSION: Patients with EV-D68 versus rhinovirus were more likely to have a history of asthma, to present with status asthmaticus, to wheeze on admission, and to receive treatment with asthma medications in hospital and at discharge. The inability of common assays to distinguish EV-D68 from rhinoviruses raises the possibility that the role of EV-D68 as a viral trigger of asthma has been under appreciated. Pediatr Pulmonol. 2017;52:827-832. © 2017 Wiley Periodicals, Inc.
Assuntos
Criança Hospitalizada/estatística & dados numéricos , Enterovirus Humano D , Infecções por Enterovirus/epidemiologia , Infecções por Picornaviridae/epidemiologia , Rhinovirus , Adolescente , Asma/epidemiologia , Criança , Pré-Escolar , Dispneia/epidemiologia , Feminino , Humanos , Lactente , Masculino , Sons Respiratórios , Estações do AnoRESUMO
BACKGROUND: Cases of pyomyositis and myositis have been increasing in frequency at Texas Children's Hospital (Houston) since 2000. The increase appears to correlate with the emergence of community-acquired methicillin-resistant Staphylococcus aureus (MRSA). METHODS: The medical records of patients with pyomyositis and myositis hospitalized at Texas Children's Hospital during the period from January 2000 through December 2005 were reviewed. Available S. aureus isolates were obtained for susceptibility testing, to determine the presence of pvl (lukS-PV and lukF-PV), and for pulsed-field gel electrophoresis analysis. RESULTS: Forty-five previously healthy children with bacterial pyomyositis or myositis were analyzed. The causes were S. aureus (in 57.8% of children) and Streptococcus pyogenes (in 2.2%); 40.0% of children had negative culture results. The number of cases increased between 2000 and 2005, primarily as a result of an increase in the prevalence of community-acquired MRSA. The mean patient age was 5.5 years (range, 0.06-15 years). The thigh (40.0% of children) and pelvis (28.9%) were the most commonly affected sites. The mean abscess diameter was 3.5 cm. Eighteen children required at least 1 muscle drainage procedure. Of the 24 available S. aureus isolates (15 community-acquired MRSA isolates and 9 community-acquired, methicillin-susceptible S. aureus [MSSA] isolates), 16 were found to be USA300 by pulsed-field gel electrophoresis, and 17 carried pvl. Patients with community-acquired MRSA, USA300, and/or pvl-positive strains required more drainage procedures than did those with community-acquired MSSA, non-USA300, and/or pvl-negative strains (81% vs. 40% [P=.05], 82% vs. 29% [P=.02], and 81% vs. 38% [P=.07], respectively). CONCLUSIONS: Community-acquired MRSA is an increasing cause of pyomyositis and myositis in children. Community-acquired MRSA, USA300, pvl-positive S. aureus isolates caused more severe disease than did community-acquired MSSA, non-USA300, and pvl-negative isolates, respectively.
Assuntos
Resistência a Meticilina , Miosite/microbiologia , Infecções Estafilocócicas , Staphylococcus aureus , Adolescente , Toxinas Bacterianas/farmacologia , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Exotoxinas/farmacologia , Feminino , Humanos , Incidência , Lactente , Leucocidinas/farmacologia , Masculino , Miosite/epidemiologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Estatísticas não Paramétricas , Texas/epidemiologiaRESUMO
BACKGROUND: After the widespread use of the 7-valent pneumococcal conjugate vaccine, replacement serotypes have emerged. Serogroups 15 and 33 have emerged as nonvaccine serotypes causing invasive disease. We describe the clinical characteristics of children with infections caused by these serogroups and determined the genetic relationship of the strains. MATERIALS AND METHODS: The United States Pediatric Multicenter Pneumococcal Surveillance Group has prospectively identified children with pneumococcal infections since 1993. Charts were reviewed retrospectively, isolates were serogrouped and serotyped and randomly selected strains were fingerprinted with the use of pulsed field gel electrophoresis. Selected strains were further characterized by multilocus sequence typing. RESULTS: Between January 1994 and December 2004, 103 children had pneumococcal disease caused by serogroup 15, and 40 children had infections caused by serogroup 33. There was an increase from a mean of 7 cases per year for serogroup 15 in the prevaccine period to 14 cases per year in the postvaccine period and from 2 cases per year for serogroup 33 to 7 cases per year in the same periods. Isolates were susceptible to penicillin and ceftriaxone in both periods. A predominant clone was found in each serogroup representing 60% (30 of 50) of serogroup 15 strains and 83% (24 of 29) of the serotype 33F strains. The serogroup 15 clone comprised strains of serotypes 15B and 15C, whereas the 33 clone contained only serotype 33F strains. One isolate from each of the 15 and 33 clones was characterized by multilocus sequence typing and were found to be ST199 and 100, respectively. CONCLUSIONS: Pneumococcal disease in children caused by penicillin-susceptible clones of serogroups 15 and 33 is increasing in the United States. Clinicians should consider replacement serotypes when encountered with invasive pneumococcal disease in vaccinated children.
Assuntos
Vacinas Meningocócicas/administração & dosagem , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/microbiologia , Vacinas Pneumocócicas/administração & dosagem , Streptococcus pneumoniae/classificação , Adolescente , Criança , Pré-Escolar , Análise por Conglomerados , Impressões Digitais de DNA/métodos , Eletroforese em Gel de Campo Pulsado , Vacina Pneumocócica Conjugada Heptavalente , Humanos , Lactente , Sorotipagem , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/patogenicidade , Estados Unidos/epidemiologia , VacinaçãoRESUMO
BACKGROUND: Staphylococcus aureus causes skin and soft tissue or invasive infections in children in the community, in the hospital or in other ways associated with the health care system (HCA). METHODS: Prospective community-acquired S. aureus infection surveillance at Texas Children's Hospital was initiated on August 1, 2001. Community onset HCA (CO HCA) infections were identified. Demographic and clinical data were collected. Antibiotic susceptibilities were determined. Data were analyzed by chi or Student's t test. CO HCO-isolates were characterized by pulsed field gel electrophoresis and staphylococcal chromosomal cassette carrying the mecA methicillin-resistant gene (SCCmec) typing. RESULTS: From August 1, 2001 to July 31, 2004, 61.5% of 322 in year 1, 62.9% of 259 in year 2 and 56.9% of 318 in year 3 of CO HCA isolates were methicillin-resistant S. aureus (MRSA). Among the CO HCA-MRSA isolates, 8.9% of 542 were from children with invasive infections compared with 24.1% of 357 CO HCA-methicillin-susceptible S. aureus (MSSA; P < 0.001). Sixty-six percent of children with CO HCA-S. aureus isolates were admitted to the hospital. Clindamycin resistance increased over the 3 years (CO HCA-MRSA, from 3.5% to 18.8%, P < 0.001; CO HCA-MSSA, from 3.2% to 10.2%, P = 0.053). Thirty-three of 35 (94.3%) CO HCA-MRSA carried SCCmecIV; 30 were USA300. Only 3 of 35 MSSA were related to USA300 by pulsed field gel electrophoresis. CONCLUSIONS: CO HCA-S. aureus infections remained steady over the 3-year study at Texas Children's Hospital. Clindamycin resistance increased >4-fold for CO HCA-S. aureus isolates over the 3 years and is no longer appropriate for empiric treatment of invasive infections suspected to be caused by CO HCA-MRSA at our hospital. In our setting, CO HCA-MRSA infections are steady in number despite substantial increases in community-acquired MRSA infections and both being related to the same clone.
Assuntos
Infecções Comunitárias Adquiridas/epidemiologia , Infecção Hospitalar/epidemiologia , Vigilância da População , Infecções Estafilocócicas/epidemiologia , Antibacterianos/farmacologia , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/microbiologia , Infecção Hospitalar/microbiologia , Humanos , Lactente , Meticilina/farmacologia , Resistência a Meticilina , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/classificação , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genéticaRESUMO
OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) isolates from patients with community-associated infection have been described as strains genetically distinct from the strains isolated from patients with healthcare-associated infection. This study examines the hypothesis that community-associated MRSA (CA-MRSA) strains now cause serious infections in hospitalized patients. METHODS: Thirty-seven clinical MRSA isolates were randomly selected from blood isolates obtained from July 2003 through June 2004. Strains were tested for staphylococcal chromosomal cassette mec (SCCmec) type, pulsed-field gel electrophoresis (PFGE) type, and presence of Panton-Valentine leukocidin (PVL) genes. Medical records review and epidemiologic classification was performed by an investigator blinded to the results of the bacterial strain analysis. Episodes of bloodstream infection were independently classified as either community-associated or healthcare-associated infections, and bacterial isolates were independently classified as either CA-MRSA strains or healthcare-associated MRSA (HA-MRSA) strains, according to established definitions. SETTING: A tertiary care Veterans Affairs Medical Center. RESULTS: Twenty-four (65%) of 37 MRSA isolates were SCCmec type IV, a genetic type characteristic of CA-MRSA strains; 22 of these 24 isolates belonged to the CA-MRSA clone USA300 and carried PVL genes. Thirteen (35%) of the 37 strains were SCCmec type II, of which 12 were USA100-ST5 and 12 lacked PVL genes. Thirty patients (81%) had healthcare-associated infections; 18 (60%) of these 30 were infected with isolates carrying markers of CA-MRSA strains. Of 7 patients with CA-MRSA infections, 6 were infected with isolates belonging to the USA300 clone. Patients with healthcare-associated bloodstream infections were as likely to be infected with a CA-MRSA strain as patients with a community-associated infection (P = .38). CONCLUSIONS: MRSA strains with molecular characteristics of CA-MRSA strains have emerged as an important cause of serious healthcare-associated infection in our hospital.
Assuntos
Infecções Comunitárias Adquiridas/microbiologia , Infecção Hospitalar/microbiologia , Resistência a Meticilina , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Toxinas Bacterianas/análise , Eletroforese em Gel de Campo Pulsado , Exotoxinas/análise , Feminino , Humanos , Leucocidinas/análise , Masculino , Pessoa de Meia-Idade , Sepse/microbiologia , Staphylococcus aureus/química , Staphylococcus aureus/genéticaRESUMO
Individuals who carry the CYP2C19*17 gain-of-function allele have lower voriconazole exposure and are therefore at risk of failing therapy. Utilizing CYP2C19 genotype to optimize voriconazole dosage may be a cost-effective method of improving treatment outcomes. However, there are limited data describing what initial voriconazole dosage should be used in those with increased CYP2C19 metabolic capacity. Herein, we present a case report of a pediatric CYP2C19 rapid metabolizer (i.e., CYP2C19*1/*17) requiring a voriconazole dosage of 14 mg/kg twice daily (usual pediatric dosage ranges from 7 to 9 mg/kg twice daily). This case report supports the clinical utility of using CYP2C19 genotype to guide voriconazole dosing, and provides data for establishing an initial voriconazole dose in pediatric CYP2C19 rapid metabolizers.
Assuntos
Antifúngicos/administração & dosagem , Antifúngicos/farmacocinética , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C19/metabolismo , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Aspergilose Pulmonar Invasiva/metabolismo , Voriconazol/administração & dosagem , Voriconazol/farmacocinética , Criança , Monitoramento de Medicamentos , Feminino , Humanos , Hospedeiro Imunocomprometido , Aspergilose Pulmonar Invasiva/cirurgia , Variantes Farmacogenômicos , Medicina de Precisão , Leucemia-Linfoma Linfoblástico de Células Precursoras B/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapiaRESUMO
BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) isolates are increasingly frequent causes of skin and soft-tissue infections or invasive infections in many communities. METHODS: Prospective surveillance for community-acquired S. aureus infections at Texas Children's Hospital was initiated on 1 August 2001. Infections meeting the definition of community-acquired were identified. Demographic and clinical data were collected. Antibiotic susceptibilities, including inducible resistance to macrolide, lincosamide, and streptogramin B (MLSB), were determined in the clinical microbiology laboratory with the methodology of the NCCLS. All data were entered into a computer database. Data were analyzed by chi2 tests. RESULTS: From 1 August 2001 to 31 July 2004, the percentage of community-acquired S. aureus isolates that were methicillin resistant increased from 71.5% (551 of 771 isolates) in year 1 to 76.4% (1193 of 1562 isolates) in year 3 (P = .008). The number of both community-acquired MRSA (CA-MSRA) isolates and community-acquired methicillin-susceptible S. aureus (CA-MSSA) isolates increased yearly, but the rate of increase was greater for the CA-MRSA isolates. Among the CA-MRSA isolates, 2542 (95.6%) were obtained from children with skin and soft-tissue infections, and 117 (4.4%) were obtained from children with invasive infections. Overall, 62% of children with CA-MRSA isolates and 53% of children with CA-MSSA isolates were admitted to the hospital (P = .0001). The rate of clindamycin resistance increased significantly for both CA-MRSA isolates (P = .003) and CA-MSSA isolates (P = .00003) over the 3 years. MLSB inducible resistance was found in 27 (44%) of 62 clindamycin-resistant CA-MSSA isolates, compared with 6 (4.5%) of 132 clindamycin-resistant CA-MRSA isolates (P < .000001). CONCLUSIONS: CA-MRSA isolates account for an increasing percentage and number of infections at Texas Children's Hospital. Clindamycin resistance increased among community-acquired S. aureus isolates. Community surveillance of community-acquired S. aureus infections is critical to determine the appropriate empiric antibiotic treatment for either local or invasive infections.
Assuntos
Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Vigilância da População , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Distribuição por Idade , Criança , Pré-Escolar , Humanos , Lactente , Resistência a Meticilina , Staphylococcus aureus/efeitos dos fármacos , Fatores de TempoRESUMO
BACKGROUND: Primary pneumonia and metastatic pulmonary infection have become more common in patients with invasive community-acquired Staphylococcus aureus disease at Texas Children's Hospital (TCH; Houston). METHODS: In this study, we sought to describe pulmonary involvement in children with community-acquired S. aureus invasive infection and to determine whether the presence of genes encoding Panton-Valentine leukocidin (PVL) (luk-S-PV and luk-F-PV) and collagen adhesin (cna) is correlated with pulmonary manifestations. Patients with invasive staphylococcal infections admitted to TCH between 1 August 2001 and 30 June 2004 were studied. Chest imaging and postmortem examination reports were reviewed. Isolates were tested for the presence of genes encoding PVL and collagen adhesin by PCR. RESULTS: A total of 47 of 70 patients with community-acquired methicillin-resistant S. aureus (MRSA) infection had abnormal pulmonary imaging findings, compared with 12 of 43 patients with community-acquired methicillin-susceptible S. aureus (MSSA) infection (P < .001). Pneumonia and/or empyema, in addition to septic emboli, were the most common findings. Metastatic pulmonary disease occurred more frequently among patients with osteomyelitis. Severe necrotizing pneumonia was present in 3 children coinfected with influenza and parainfluenza virus. The presence of genes encoding PVL was investigated in 67 MRSA and 36 MSSA isolates. Abnormal chest imaging findings were observed for 51 of 80 patients with PVL-positive isolates, compared with 2 of 23 patients with PVL-negative isolates (P < .001). Only 2 isolates (both of which were MSSA) from patients with abnormal chest radiograph findings carried cna. PVL remained independently associated with abnormal chest imaging findings in patients with secondary pneumonia in a multivariate analysis (P = .03). CONCLUSIONS: Pulmonary involvement is commonly observed in patients with invasive community-acquired S. aureus infections. Community-acquired MRSA may cause primary community-acquired pneumonia, as well as metastatic pulmonary disease. The presence of genes encoding PVL is highly associated with pulmonary involvement by S. aureus.