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Daptomycin is one of the few treatment options for infections caused by enterococci that are resistant to ampicillin and vancomycin, such as vancomycin-resistant Enterococcus faecium. The emergence and clinical significance of daptomycin-resistant enterococci and evolving microbiologic, pharmacokinetic-pharmacodynamic, and clinical data indicated that the pre-2019 Clinical and Laboratory Standards Institute (CLSI) susceptible-only breakpoint of ≤4 µg/mL for daptomycin and enterococci was no longer appropriate. After analyzing data that are outlined in this article, the CLSI Subcommittee on Antimicrobial Susceptibility Testing established new breakpoints for daptomycin and enterococci. For E. faecium, a susceptible dose-dependent (SDD) breakpoint of ≤4 µg/mL was established based on an increased dosage of 8-12 mg/kg/day (≥8 µg/mL-resistant). CLSI suggests infectious diseases consultation to guide daptomycin use for the SDD category. For Enterococcus faecalis and other enterococcal species, revised breakpoints of ≤2 µg/mL-susceptible, 4 µg/mL-intermediate, and ≥8 µg/mL-resistant were established based on a standard dosage of 6 mg/kg/day.
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Daptomicina , Enterococcus faecium , Infecções por Bactérias Gram-Positivas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Daptomicina/farmacologia , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Laboratórios , Testes de Sensibilidade Microbiana , Padrões de ReferênciaRESUMO
SETTING: Five health care systems in Texas. OBJECTIVE: To describe the epidemiology of inadequate isolation for pulmonary tuberculosis leading to tuberculosis (TB) exposures from confirmed TB patients and the patient factors that led to the exposures. DESIGN: A retrospective cohort and case-control study of adult patients with TB resulting in exposures (cases) vs those TB patients who did not result in exposures (controls) during January 2005 to December 2012. RESULTS: There were 335 patients with pulmonary TB disease, 199 cases and 136 controls. There was no difference between groups in age (46 ± 14.6 vs 45 ± 17 years; P > .05), race, or substance abuse. Cases were more likely to be transplant recipients (adjusted odds ratio [AOR], 18.90; 95% CI, 1.9-187.76), have typical TB chest radiograph (AOR, 2.23; 95% CI, 1.1-4.51), and have positive acid-fast bacilli stains (AOR, 2.36; 95% CI, 1.31-4.27). Cases were less likely to have extrapulmonary disease (AOR, 0.47; 95% CI, 0.24-0.95). CONCLUSIONS: TB exposure resulting from inadequate isolation is frequent in health care settings. Extrapulmonary involvement resulted in earlier airborne isolation. Being a transplant recipient, having chest radiograph findings typical for TB, and sputum positivity acid-fast bacilli upon staining were associated with increased risk of inadequate isolation.
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Streptococcus anginosus is a member of the normal oral flora that can become a pathogen causing pyogenic infections in humans. The genome of daptomycin-resistant strain J4206, originally isolated from a patient suffering from breakthrough bacteremia and septic shock at the University of Texas Health Science Center at San Antonio, was determined. The circular genome is 2,001,352 bp long with a GC content of 38.62% and contains multiple mobile genetic elements, including the phage-like chromosomal island SanCI that mediates a mutator phenotype, transposons, and integrative conjugative elements. Daptomycin resistance involves multiple alterations in the cell membrane and cell wall, and unique features were identified in J4206 that may contribute to resistance. A cluster of capsular polysaccharide (CPS) genes for choline metabolism and transport are present that may help neutralize cell surface charges, destabilizing daptomycin binding. Further, unique J4206 genes encoding sortases and LPXTG-target proteins that are involved in cell wall modification were present. The J4206 genome is phylogenetically closely related to the recently reported vancomycin-resistant SA1 strain; however, these genomes differ with SNPs in cardiolipin synthetase, histidine kinase yycG, teichoic acid modification genes, and other genes involved in cell surface modification. Transmission electron microscopy showed that the cell walls of both strains J4206 and SA1 were significantly thicker and more electron dense than daptomycin- and vancomycin-sensitive strain J4211. This comparative genomic study has identified unique genes as well as allelic variants in the J4206 genome that are involved in cell surface modification and thus might contribute to the acquisition of daptomycin resistance.
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Antibacterianos/farmacologia , Bacteriemia/microbiologia , Daptomicina/farmacologia , Farmacorresistência Bacteriana/genética , Genoma Bacteriano , Streptococcus anginosus/genética , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Composição de Bases , Parede Celular/metabolismo , Parede Celular/ultraestrutura , Colina/genética , Colina/metabolismo , Elementos de DNA Transponíveis , Daptomicina/uso terapêutico , Endopeptidases/genética , Endopeptidases/metabolismo , Humanos , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Streptococcus anginosus/efeitos dos fármacos , Streptococcus anginosus/isolamento & purificação , Vancomicina/farmacologia , Vancomicina/uso terapêuticoRESUMO
BACKGROUND: In 2010, 13-valent pneumococcal conjugate vaccine (PCV13) was licensed and recommended in the USA for prevention of invasive pneumococcal disease in children. Licensure was based on immunogenicity data comparing PCV13 with the earlier seven-valent formulation. Because clinical endpoints were not assessed for the new antigens, we did a postlicensure matched case-control study to assess vaccine effectiveness. METHODS: Cases in children aged 2-59 months were identified through active surveillance in 13 sites. Controls were identified via birth registries and matched to cases by age and postal (zip) code. The primary objective was the vaccine effectiveness of at least one dose against the 13 serotypes included in PCV13. Secondary objectives included vaccine effectiveness against all-cause invasive pneumococcal disease, against antibiotic non-susceptible invasive pneumococcal disease, and among children with and without underlying conditions. Vaccine effectiveness was calculated as (1â-âmatched odds ratio)â×â100%. FINDINGS: We enrolled 722 children with invasive pneumococcal disease and 2991 controls; PCV13 serotype cases (217 [30%]) included most commonly serotypes 19A (128 [18%]), 7F (32 [4%]), and 3 (43 [6%]). Vaccine effectiveness against PCV13 serotypes was 86·0% (95% CI 75·5 to 92·3), driven by serotypes 19A and 7F, for which vaccine effectiveness was 85·6% (95% CI 70·6 to 93·5) and 96·5% (82·7 to 100), respectively. We also identified statistically significant effectiveness against serotype 3 (79·5%, 95% CI 30·3 to 94·8) and against antibiotic non-susceptible invasive pneumococcal disease (65·6%, 44·9 to 78·7). Vaccine effectiveness against all-cause invasive pneumococcal disease was 60·2% (95% CI 46·8 to 70·3). Vaccine effectiveness was similar among children with (81·4%, 95% CI 45·4 to 93·6) and without (85·8%, 74·9 to 91·9) underlying conditions. INTERPRETATION: PCV13 appears highly effective against invasive pneumococcal disease among children in the USA in the context of routine and catch-up schedules, although some new vaccine antigens could not be assessed. PCV13 immunisation provides a robust strategy for combating pneumococcal antimicrobial resistance. FUNDING: Centers for Disease Control and Prevention.
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Vacinação em Massa/estatística & dados numéricos , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/uso terapêutico , Estudos de Casos e Controles , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Vacinação em Massa/métodos , Sistema de Registros , Resultado do Tratamento , Estados UnidosRESUMO
PURPOSE: To assess the potency and sterility of ophthalmic antibiotic drops commonly used in the treatment of bacterial keratitis. METHODS: This was a basic investigation. Three drugs were tested: fortified vancomycin 25 mg/mL, fortified tobramycin 14 mg/mL, and moxifloxacin 5 mg/mL. A bottle of each was stored separately at 4, 24, and 35°C, with the potency determined by microbiological assay at 0, 7, and 14 days. Differences in potency were assessed by 2-way analysis of variance followed by a 1-way repeated-measures analysis of variance with Bonferroni post hoc testing as warranted. Sterility of drugs when handled by patients for varying periods was confirmed by culturing samples on MacConkey and sheep blood agars. RESULTS: The concentration of fortified tobramycin and moxifloxacin remained constant over 14 days at the 3 tested temperatures. The concentration of fortified vancomycin remained constant at 4°C, but it declined by 38% ± 1% (P = 0.001) at 24°C on day 14 and by 48% ± 1% (P = 0.001) and 78% ± 3% (P = 0.0009) at 35°C on days 7 and 14, respectively. A total of 49 drops (mean, 7.3 days; range, 1-18 days) were tested for sterility, and all were negative for microbial contamination. CONCLUSIONS: All 3 drugs remained potent at 4°C for up to 14 days. Fortified tobramycin and moxifloxacin also maintained potency for 14 days at 24 and 35°C. In contrast, fortified vancomycin lost its potency by day 14 at 24°C and by day 7 at 35°C. All in-use antibiotic drops tested were sterile. The results indicate that patients should be cautioned to store vancomycin under refrigerator or at least under cool conditions.
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Antibacterianos/farmacologia , Fluoroquinolonas/farmacologia , Tobramicina/farmacologia , Vancomicina/farmacologia , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Infecções Oculares Bacterianas/tratamento farmacológico , Seguimentos , Humanos , Infertilidade , Ceratite/tratamento farmacológico , Testes de Sensibilidade Microbiana , Moxifloxacina , Soluções Oftálmicas/farmacologia , Estudos Prospectivos , Temperatura , Fatores de TempoRESUMO
Streptococcus anginosus is an opportunistic human pathogen that causes abscesses of the brain, liver, and other organs. Here, we announce the complete genome sequence of a clinically isolated strain of S. anginosus J4211. The genome sequence contains two prophages and multiple mobile genetic elements.
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BACKGROUND: In 2000, seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in the USA and resulted in dramatic reductions in invasive pneumococcal disease (IPD) and moderate increases in non-PCV7 type IPD. In 2010, PCV13 replaced PCV7 in the US immunisation schedule. We aimed to assess the effect of use of PCV13 in children on IPD in children and adults in the USA. METHODS: We used laboratory-based and population-based data on incidence of IPD from the Active Bacterial Core surveillance (part of the Centers for Disease Control and Prevention's Emerging Infections Program) in a time-series model to compare rates of IPD before and after the introduction of PCV13. Cases of IPD between July 1, 2004, and June 30, 2013, were classified as being caused by the PCV13 serotypes against which PCV7 has no effect (PCV13 minus PCV7). In a time-series model, we used an expected outcomes approach to compare the reported incidence of IPD to that which would have been expected if PCV13 had not replaced PCV7. FINDINGS: Compared with incidence expected among children younger than 5 years if PCV7 alone had been continued, incidence of IPD overall declined by 64% (95% interval estimate [95% IE] 59-68) and IPD caused by PCV13 minus PCV7 serotypes declined by 93% (91-94), by July, 2012, to June, 2013. Among adults, incidence of IPD overall also declined by 12-32% and IPD caused by PCV13 minus PCV7 type IPD declined by 58-72%, depending on age. We estimated that over 30â000 cases of IPD and 3000 deaths were averted in the first 3 years after the introduction of PCV13. INTERPRETATION: PCV13 reduced IPD across all age groups when used routinely in children in the USA. These findings provide reassurance that, similar to PCV7, PCVs with additional serotypes can also prevent transmission to unvaccinated populations. FUNDING: Centers for Disease Control and Prevention.
Assuntos
Bacteriemia/epidemiologia , Bacteriemia/prevenção & controle , Meningites Bacterianas/epidemiologia , Meningites Bacterianas/prevenção & controle , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Vacinas Pneumocócicas/administração & dosagem , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto JovemRESUMO
BACKGROUND: A clinical trial of mass azithromycin distributions for trachoma created a convenient experiment to test the hypothesis that antibiotic use selects for clonal expansion of preexisting resistant bacterial strains. METHODS: Twelve communities in Ethiopia received mass azithromycin distributions every 3 months for 1 year. A random sample of 10 children aged 0-9 years from each community was monitored by means of nasopharyngeal swab sampling before mass azithromycin distribution and after 4 mass treatments. Swab specimens were tested for Streptococcus pneumoniae, and isolates underwent multilocus sequence typing. RESULTS: Of 82 pneumococcal isolates identified before treatment, 4 (5%) exhibited azithromycin resistance, representing 3 different sequence types (STs): 177, 6449, and 6494. The proportion of isolates that were classified as one of these 3 STs and were resistant to azithromycin increased after 4 mass azithromycin treatments (14 of 96 isolates [15%]; P = .04). Using a classification index, we found evidence for a relationship between ST and macrolide resistance after mass treatments (P < .0001). The diversity of STs-as calculated by the unbiased Simpson index-decreased significantly after mass azithromycin treatment (P = .045). CONCLUSIONS: Resistant clones present before mass azithromycin treatments increased in frequency after treatment, consistent with the theory that antibiotic selection pressure results in clonal expansion of existing resistant strains.
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Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Infecções Pneumocócicas/microbiologia , Streptococcus pneumoniae/efeitos dos fármacos , Criança , Pré-Escolar , Farmacorresistência Bacteriana , Feminino , Genes Bacterianos , Humanos , Lactente , Recém-Nascido , Masculino , Tipagem de Sequências Multilocus , Cavidade Nasal/microbiologia , Infecções Pneumocócicas/tratamento farmacológico , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/isolamento & purificaçãoRESUMO
Multidrug-resistant Acinetobacter baumannii is among the most prevalent bacterial pathogens associated with trauma-related wound and bloodstream infections. Although septic shock and disseminated intravascular coagulation have been reported following fulminant A. baumannii sepsis, little is known about the protective host immune response to this pathogen. In this study, we examined the role of PTX3, a soluble pattern recognition receptor with reported antimicrobial properties and stored within neutrophil granules. PTX3 production by murine J774a.1 macrophages was assessed following challenge with A. baumannii strains ATCC 19606 and clinical isolates (CI) 77, 78, 79, 80, and 86. Interestingly, only CI strains 79, 80, and 86 induced PTX3 synthesis in murine J774a.1 macrophages, with greatest production observed following CI 79 and 86 challenge. Subsequently, C57BL/6 mice were challenged intraperitoneally with CI 77 and 79 to assess the role of PTX3 in vivo. A. baumannii strain CI 79 exhibited significantly (P < 0.0005) increased mortality, with an approximate 50% lethal dose (LD50) of 10(5) CFU, while an equivalent dose of CI 77 exhibited no mortality. Plasma leukocyte chemokines (KC, MCP-1, and RANTES) and myeloperoxidase activity were also significantly elevated following challenge with CI 79, indicating neutrophil recruitment/activation associated with significant elevation in serum PTX3 levels. Furthermore, 10-fold-greater PTX3 levels were observed in mouse serum 12 h postchallenge, comparing CI 79 to CI 77 (1,561 ng/ml versus 145 ng/ml), with concomitant severe pathology (liver and spleen) and coagulopathy. Together, these results suggest that elevation of PTX3 is associated with fulminant disease during A. baumannii sepsis.
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Acinetobacter baumannii/imunologia , Proteína C-Reativa/imunologia , Proteínas do Tecido Nervoso/imunologia , Sepse/imunologia , Choque Séptico/imunologia , Infecções por Acinetobacter/sangue , Infecções por Acinetobacter/imunologia , Infecções por Acinetobacter/microbiologia , Animais , Linhagem Celular , Quimiocinas/sangue , Macrófagos/imunologia , Macrófagos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/imunologia , Monócitos/microbiologia , Proteínas do Tecido Nervoso/sangue , Neutrófilos/imunologia , Neutrófilos/microbiologia , Peroxidase/sangue , Sepse/sangue , Sepse/microbiologia , Choque Séptico/sangue , Choque Séptico/mortalidadeRESUMO
Acinetobacter baumannii is among the most prevalent bacterial causes of combat-related infections on the battlefield. Antibiotic resistance and a poor understanding of the protective host immune responses make treatment difficult. Here, we report the genome sequences of four clinical Acinetobacter baumannii-A. calcoaceticus complex isolates exhibiting significant differences in virulence in a mouse sepsis model.
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Inducible clindamycin resistance in beta-hemolytic streptococci remains an underrecognized phenomenon of unknown clinical significance. We performed an evaluation of inducible clindamycin resistance using an animal model as well as retrospectively reviewing the charts of patients treated with clindamycin monotherapy who were infected with beta-hemolytic streptococci inducibly resistant to clindamycin. The neutropenic mouse thigh model of infection was used to evaluate the in vivo activity of clindamycin against beta-hemolytic streptococci, including isolates susceptible, inducibly resistant, or constitutively resistant to clindamycin. The clinical microbiology laboratory information system and pharmacy databases were cross-referenced to identify patients with infections due to inducibly clindamycin-resistant beta-hemolytic streptococci who were treated with clindamycin monotherapy. Medical records of these patients were reviewed to evaluate microbiologic and clinical outcomes. Inducible clindamycin resistance resulted in impaired killing of beta-hemolytic streptococci in the animal model. Though suppressed initially, compared to those with constitutive resistance (P=0.0429), by 48 h, colony counts of inducibly clindamycin-resistant organisms were similar to those of constitutively resistant isolates (P=0.1142). In addition, we identified 8 patients infected with inducibly clindamycin-resistant beta-hemolytic streptococci who experienced clinical and microbiologic failure when treated with clindamycin monotherapy. These patients either improved initially and subsequently failed or never responded to clindamycin therapy. We have demonstrated in a murine model of infection and from human cases that inducible clindamycin resistance in beta-hemolytic streptococci is clinically significant. Routine testing and reporting by clinical laboratories should be encouraged and alternative antimicrobial agents considered when these organisms are encountered in clinical care.
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Antibacterianos/uso terapêutico , Clindamicina/uso terapêutico , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus/efeitos dos fármacos , Adulto , Animais , Modelos Animais de Doenças , Farmacorresistência Bacteriana , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Pessoa de Meia-Idade , Estudos Retrospectivos , Falha de TratamentoRESUMO
Carbapenem-resistant Enterobacteriaceae infections are becoming more common, are associated with high mortality rates, and are difficult to treat due to multiple mechanisms of resistance. We describe the successful treatment of Klebsiella pneumoniae carbapenemase-expressing Enterobacter cloacae empyema in a lung transplant recipient with cefepime and levofloxacin.
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Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Empiema/tratamento farmacológico , Empiema/microbiologia , Enterobacter cloacae/genética , Infecções por Enterobacteriaceae/tratamento farmacológico , Levofloxacino/uso terapêutico , beta-Lactamases/genética , Cefepima , Quimioterapia Combinada , Empiema/diagnóstico , Infecções por Enterobacteriaceae/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: We examined whether observed increases in antibiotic nonsusceptible nonvaccine serotypes after introduction of pneumococcal conjugate vaccine in the United States in 2000 were driven primarily by vaccine or antibiotic use. METHODS: Using active surveillance data, we evaluated geographic and temporal differences in serotype distribution and within-serotype differences during 2000-2009. We compared nonsusceptibility to penicillin and erythromycin by geography after standardizing differences across time, place, and serotype by regressing standardized versus crude proportions. A regression slope (RS) approaching zero indicates greater importance of the standardizing factor. RESULTS: Through 2000-2006, geographic differences in nonsusceptibility were better explained by within-serotype prevalence of nonsusceptibility (RS 0.32, 95% confidence interval [CI], .08-.55 for penicillin) than by geographic differences in serotype distribution (RS 0.71, 95% CI, .44-.97). From 2007-2009, serotype distribution differences became more important for penicillin (within-serotype RS 0.52, 95% CI, .11-.93; serotype distribution RS 0.57, 95% CI, .14-1.0). CONCLUSIONS: Differential nonsusceptibility, within individual serotypes, accounts for most geographic variation in nonsusceptibility, suggesting selective pressure from antibiotic use, rather than differences in serotype distribution, mainly determines nonsusceptibility patterns. Recent trends suggest geographic differences in serotype distribution may be affecting the prevalence of nonsusceptibility, possibly due to decreases in the number of nonsusceptible serotypes.
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Antibacterianos/farmacologia , Infecções Pneumocócicas/microbiologia , Vacinas Pneumocócicas/administração & dosagem , Streptococcus pneumoniae/efeitos dos fármacos , Farmacorresistência Bacteriana , Eritromicina/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Penicilinas/farmacologia , Infecções Pneumocócicas/epidemiologia , Vigilância em Saúde Pública , Análise de Regressão , Estatísticas não Paramétricas , Streptococcus pneumoniae/isolamento & purificação , Estados Unidos/epidemiologiaRESUMO
We report a case of Candida glabrata candidemia that developed resistance to micafungin within 8 days of initiation of therapy in a patient without previous echinocandin exposure or other known risk factors for clinical or microbiological failure. Pre- and postresistant isolates were confirmed to be isogenic, and sequencing of hot spots known to confer echinocandin resistance revealed a phenylalanine deletion at codon 659 within FKS2.
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Antifúngicos/farmacologia , Candida glabrata/efeitos dos fármacos , Candidemia/tratamento farmacológico , Farmacorresistência Fúngica/genética , Equinocandinas/farmacologia , Proteínas Fúngicas/genética , Glucosiltransferases/genética , Candida glabrata/enzimologia , Candida glabrata/genética , Candidemia/microbiologia , Farmacorresistência Fúngica/efeitos dos fármacos , Feminino , Proteínas Fúngicas/metabolismo , Glucosiltransferases/metabolismo , Humanos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mutação , Análise de Sequência de DNA , Fatores de TempoRESUMO
BACKGROUND: Children with sickle cell disease (SCD) are at increased risk of illness and death from invasive pneumococcal disease (IPD). The introduction in 2000 of the 7-valent pneumococcal conjugate vaccine and penicillin prophylaxis for children with SCD has greatly reduced the incidence of IPD in this population. However, a recent report suggested an increase in cases of IPD in children with SCD. METHODS: Using data from Active Bacterial Core surveillance, we analyzed trends in hospitalizations, mortality and serotype among children with SCD compared with other children. We used neonatal screening data to estimate SCD population denominators for each Active Bacterial Core surveillance site. RESULTS: From 1998 to 2009, 3069 cases of IPD occurred among African-American children less than 18 years of age in the Active Bacterial Core surveillance catchment area. Of these, 127 (4.1%) had SCD identified by medical chart review and 185 (6.0%) had 1 or more IPD risk factors, excluding SCD. Rates of IPD among children with SCD declined by 53% (1118 vs. 530 per 100,000) whereas the overall rates among African-American children declined by 74% (54 to 14 per 100,000). For all time periods, children with SCD and IPD were more likely to be hospitalized (84%-92% vs. 31%-56%) and more likely to die (6%-17% vs. 1%-2%) than children with no risk factors. CONCLUSIONS: Although the rate of IPD in children with SCD has dropped dramatically since 7-valent pneumococcal conjugate vaccine introduction, the rate of IPD in children with SCD remains higher than that of the general population of African-American children, pointing to the need for more effective prevention efforts to prevent IPD in children with SCD.
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Anemia Falciforme/epidemiologia , Infecções Pneumocócicas/epidemiologia , Adolescente , Negro ou Afro-Americano , Anemia Falciforme/microbiologia , Criança , Pré-Escolar , Vacina Pneumocócica Conjugada Heptavalente , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Lactente , Recém-Nascido , Infecções Pneumocócicas/sangue , Vacinas Pneumocócicas/administração & dosagem , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
A study was performed to derive susceptibility testing interpretive breakpoints for doxycycline with Streptococcus pneumoniae and to reassess breakpoints for tetracycline using the requirements defined in Clinical and Laboratory Standards Institute (CLSI) document M23-A3. Tetracycline and doxycycline MICs and disk diffusion zone sizes were determined on 189 isolates selected from the 2009-2010 CDC Active Bacterial Core surveillance strain collection according to the testing methods described in CLSI documents M07-A8 and M02-A10. Tetracycline and doxycycline MICs and zones were compared to each other directly, and the reproducibility of MICs and zone diameters for both drugs was determined. Scattergrams of tetracycline MICs versus corresponding zone diameters and doxycycline MICs versus zones were prepared, and analysis indicated that the present CLSI tetracycline MIC and disk breakpoints did not fit the susceptibility data for doxycycline. Doxycycline was 1 to 3 dilutions more potent than tetracycline, especially in strains harboring the tetM resistance determinant. tetM was detected in ≥ 90% of isolates having tetracycline MICs of ≥ 4 µg/ml and in ≥ 90% with doxycycline MICs of ≥ 1. Limited pharmacokinetic/pharmacodynamic (PK/PD) data coupled with application of the error-rate bounded method of analysis suggested doxycycline-susceptible breakpoints of either ≤ 0.25 µg/ml or ≤ 0.5 µg/ml, with intermediate and resistant breakpoints 1 and 2 dilutions higher, respectively. The disk diffusion zone diameter correlates were susceptible at ≥ 28 mm, intermediate at 25 to 27 mm, and resistant at ≤ 24 mm. Revised lower tetracycline MIC breakpoints were suggested as susceptible at ≤ 1 µg/ml, intermediate at 2 µg/ml, and resistant at ≥ 4 µg/ml. Suggested tetracycline disk diffusion zones were identical to those of doxycycline.
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Antibacterianos/farmacologia , Doxiciclina/farmacologia , Streptococcus pneumoniae/efeitos dos fármacos , Tetraciclina/farmacologia , Humanos , Testes de Sensibilidade Microbiana/métodos , Testes de Sensibilidade Microbiana/normas , Reprodutibilidade dos TestesRESUMO
Microsporidia are increasingly recognized as opportunistic pathogens in immunocompromised organ transplant recipients (OTR). Disseminated infection due to Encephalitozoon sp. is reported mainly in human immunodeficiency virus (HIV)-positive patients and rarely in HIV-negative OTR. The clinical spectrum ranges from keratoconjunctivitis, to pneumonitis, to acute kidney injury. The kidney is a common site for disseminated infection; however, specialized techniques are required for definitive diagnosis. We report the first case of disseminated Encephalitozoon cuniculi infection in an HIV-negative lung transplant recipient diagnosed on renal biopsy. Five months after transplant, he presented with fever and a lung infiltrate and developed acute kidney injury. Renal biopsy showed granulomatous interstitial nephritis with gram-positive rod-shaped organisms with a "belt-like stripe" in tubular epithelial cells. Electron microscopy, polymerase chain reaction, and mammalian cell cultures of the urine sediment confirmed E. cuniculi infection. Retrospective review of a previous lung biopsy showed similar organisms. On the basis of electron microscopy findings, the patient was treated with albendazole, and immunosuppressive therapy was reduced. However, the patient expired due to Aspergillus pneumonia and disseminated E. cuniculi infection. Microsporidia should be considered in cases of fever of unknown origin and/or multiorgan infection in HIV-negative OTR when other causes have been excluded, as successful treatment requires early detection.
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Encefalitozoonose/imunologia , Hospedeiro Imunocomprometido , Nefrite Intersticial/diagnóstico , Nefrite Intersticial/microbiologia , Albendazol/uso terapêutico , Antifúngicos/uso terapêutico , Encephalitozoon cuniculi , Encefalitozoonose/tratamento farmacológico , Evolução Fatal , Granuloma/diagnóstico , Granuloma/microbiologia , Humanos , Transplante de Pulmão , Masculino , Pessoa de Meia-IdadeRESUMO
Background. The occurrence of community-associated infections due to extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli has been recognized as a major clinical problem in Europe and other regions. Methods. We conducted a prospective observational study to examine the occurrence of community-associated infections due to ESBL-producing E. coli at centers in the United States. Five academic and community hospitals and their affiliated clinics participated in this study in 2009 and 2010. Sites of acquisition of the organisms (community-associated or healthcare-associated), risk factors, and clinical outcome were investigated. Screening for the global epidemic sequence type (ST) 131 and determination of the ESBL types was conducted by polymerase chain reaction and sequencing. Results. Of the 291 patients infected or colonized with ESBL-producing E. coli as outpatients or within 48 hours of hospitalization, 107 (36.8%) had community-associated infection (81.5% of which represented urinary tract infection), while the remainder had healthcare-associated infection. Independent risk factors for healthcare-associated infection over community-associated infection were the presence of cardiovascular disease, chronic renal failure, dementia, solid organ malignancy, and hospitalization within the previous 12 months. Of the community-associated infections, 54.2% were caused by the globally epidemic ST131 strain, and 91.3% of the isolates produced CTX-M-type ESBL. Conclusions. A substantial portion of community-onset, ESBL-producing E. coli infections now occur among patients without discernible healthcare-associated risk factors in the United States. This epidemiologic shift has implications for the empiric management of community-associated infection when involvement of E. coli is suspected.
Assuntos
Infecções Comunitárias Adquiridas/epidemiologia , Infecções por Escherichia coli/epidemiologia , Escherichia coli/enzimologia , beta-Lactamases/metabolismo , Infecções Comunitárias Adquiridas/microbiologia , Infecções por Escherichia coli/microbiologia , Humanos , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
Carbapenemase detection has become a major problem in hospitals that encounter outbreaks of infections caused by carbapenem-resistant Gram-negative bacteria. Rapid detection systems have been reported using multiplex PCR analyses and DNA microarray assays. Major carbapenemases that are detected by these systems include the KPC and OXA serine carbapenemases, and the IMP, VIM and NDM families of metallo-ß-lactamases. However, increasing numbers of the SME serine carbapenemase are being reported from Serratia marcescens, especially from North and South America. These organisms differ from many of the other carbapenemase-producing pathogens in that they are generally susceptible to the expanded-spectrum cephalosporins ceftazidime and cefepime while retaining resistance to almost all other ß-lactam antibiotics. Thus, multiplex PCR assays or DNA microarray testing of carbapenem-resistant S. marcescens isolates should include analyses for production of the SME carbapenemase. Confirmation of the presence of this enzyme may provide reassurance that oxyimino-cephalosporins can be considered for treatment of infections caused by these carbapenem-resistant pathogens.
Assuntos
Proteínas de Bactérias/genética , Técnicas Bacteriológicas/métodos , Reação em Cadeia da Polimerase Multiplex/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Serratia marcescens/enzimologia , beta-Lactamases/genética , Humanos , América do Norte , Infecções por Serratia/microbiologia , Serratia marcescens/genética , Serratia marcescens/isolamento & purificação , América do SulRESUMO
In this prospective, observational study of 618 consecutive adult patients with skin and soft tissue infections (SSTI) caused by methicillin-resistant Staphylococcus aureus (MRSA), the clinical characteristics, molecular epidemiology, and outcome of patients with clindamycin-resistant MRSA (n = 64) and clindamycin-susceptible MRSA (n = 554) were compared (including factors predictive of clindamycin-resistant MRSA SSTI). Patients with clindamycin-resistant MRSA were more likely to have had antibiotic exposure within 3 months (37.5% versus 17%, P < 0.01), surgery (25% versus 8%, P < 0.01), MRSA infection/colonization within 12 months (23% versus 7%, P < 0.01), or intravascular catheters (5% versus 0.5%, P = 0.02). On multivariate analysis, previous surgery (adjusted odds ratio [AOR] 2.97; 95% confidence interval [CI] 1.5-6.0), history of MRSA (AOR 3.4; 95% CI 1.7-7.1), and exposure to clindamycin (AOR 8.5; 95% CI 2.3-32) and to macrolides (AOR 7.2, 95% CI 1.6-31.8) were independently associated with presence of clindamycin-resistant MRSA. Clinical resolution was similar between groups (77% versus 68%; P = 0.26). Clindamycin-resistant MRSA was less often USA-300 (82% versus 98%, P = 0.004). Clindamycin resistance did not affect MRSA-SSTI clinical outcomes.