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BACKGROUND: Cerebral malaria (CM) pathogenesis remains incompletely understood. Having shown low systemic levels of tetrahydrobiopterin (BH4), an enzymatic cofactor for neurotransmitter synthesis, we hypothesized that BH4 and BH4-dependent neurotransmitters would likewise be low in cerebrospinal fluid (CSF) in CM. METHODS: We prospectively enrolled Tanzanian children with CM and children with nonmalaria central nervous system conditions (NMCs). We measured CSF levels of BH4, neopterin, and BH4-dependent neurotransmitter metabolites, 3-O-methyldopa, homovanillic acid, and 5-hydroxyindoleacetate, and we derived age-adjusted z-scores using published reference ranges. RESULTS: Cerebrospinal fluid BH4 was elevated in CM (nâ =â 49) compared with NMC (nâ =â 51) (z-score 0.75 vs -0.08; Pâ <â .001). Neopterin was increased in CM (z-score 4.05 vs 0.09; Pâ <â .001), and a cutoff at the upper limit of normal (60 nmol/L) was 100% sensitive for CM. Neurotransmitter metabolite levels were overall preserved. A higher CSF BH4/BH2 ratio was associated with increased odds of survival (odds ratio, 2.94; 95% confidence interval, 1.03-8.33; Pâ =â .043). CONCLUSION: Despite low systemic BH4, CSF BH4 was elevated and associated with increased odds of survival in CM. Coma in malaria is not explained by deficiency of BH4-dependent neurotransmitters. Elevated CSF neopterin was 100% sensitive for CM diagnosis and warrants further assessment of its clinical utility for ruling out CM in malaria-endemic areas.
Assuntos
Biopterinas/líquido cefalorraquidiano , Malária Cerebral/mortalidade , Neopterina/líquido cefalorraquidiano , Neurotransmissores/líquido cefalorraquidiano , Pterinas/líquido cefalorraquidiano , Biopterinas/análogos & derivados , Doenças do Sistema Nervoso Central/líquido cefalorraquidiano , Criança , Pré-Escolar , Feminino , Ácido Homovanílico/líquido cefalorraquidiano , Humanos , Ácido Hidroxi-Indolacético/líquido cefalorraquidiano , Lactente , Malária Cerebral/líquido cefalorraquidiano , Masculino , Estudos Prospectivos , Valores de Referência , Tanzânia/epidemiologia , Tirosina/análogos & derivadosRESUMO
Background: Rapid diagnostic tests (RDTs) for bacteremia allow for early antimicrobial therapy modification based on organism and resistance gene identification. Studies suggest patient outcomes are optimized when infectious disease (ID)-trained antimicrobial stewardship personnel intervene on RDT results. However, data are limited regarding RDT implementation at small community hospitals, which often lack access to on-site ID clinicians. Methods: This study evaluated the impact of RDTs with and without real-time pharmacist intervention (RTPI) at a small community hospital with local pharmacist training and asynchronous support from a remote ID Telehealth pharmacist. Time to targeted therapy (TTT) in patients with bacteremia was compared retrospectively across 3 different time periods: a control without RDT, RDT-only, and RDT with RTPI. Results: Median TTT was significantly faster in both the RDT with RTPI and RDT-only groups compared with the control group (2 vs 25 vs 51 hours respectively; P < .001). TTT was numerically faster for RDT with RTPI compared with RDT-only but did not reach statistical significance (P = .078). Median time to any de-escalation was significantly shorter for RDT with RTPI compared with both RDT-only (14 vs 33 hours; P = .012) and the control group (14 vs 45 hours; P < .001). Median length of stay was also significantly shorter in both RDT groups compared with the control group (4.0 vs 4.1 vs 5.5 hours; P = .013). Conclusion: This study supports RDT use for bacteremia in a small community hospital with ID Telehealth support, suggesting additional benefit with RTPI.
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BACKGROUND: Antibiotic stewardship is challenging in hematological malignancy patients. METHODS: We performed a quasiexperimental implementation study of 2 antimicrobial stewardship interventions in a hematological malignancy unit: monthly antibiotic cycling for febrile neutropenia that included cefepime (± metronidazole) and piperacillin-tazobactam and a clinical prediction rule to guide anti-vancomycin-resistant Enterococcus faecium (VRE) therapy. We used interrupted time-series analysis to compare antibiotic use and logistic regression in order to adjust observed unit-level changes in resistant infections by background community rates. RESULTS: A total of 2434 admissions spanning 3 years pre- and 2 years postimplementation were included. Unadjusted carbapenem and daptomycin use decreased significantly. In interrupted time-series analysis, carbapenem use decreased by -230 days of therapy (DOT)/1000 patient-days (95% confidence interval [CI], -290 to -180; P < .001). Both VRE colonization (odds ratio [OR], 0.64; 95% CI, 0.51 to 0.81; P < .001) and infection (OR, 0.41; 95% CI, 0.2 to 0.9; P = .02) decreased after implementation. This shift may have had a greater effect on daptomycin prescribing (-160 DOT/1000 patient-days; 95% CI, -200 to -120; P < .001) than did the VRE clinical prediction score (-30 DOT/1000 patient-days; 95% CI, -50 to 0; P = .08). Also, 46.2% of Pseudomonas aeruginosa isolates were carbapenem-resistant preimplementation compared with 25.0% postimplementation (P = .32). Unit-level changes in methicillin-resistant Staphylococcus aureus and extended-spectrum beta lactamase (ESBL) incidence were explained by background community-level trends, while changes in AmpC ESBL and VRE appeared to be independent. The program was not associated with increased mortality. CONCLUSIONS: An antibiotic cycling-based strategy for febrile neutropenia effectively reduced carbapenem use, which may have resulted in decreased VRE colonization and infection and perhaps, in turn, decreased daptomycin prescribing.
Assuntos
Gestão de Antimicrobianos , Infecções por Bactérias Gram-Positivas , Neoplasias Hematológicas , Staphylococcus aureus Resistente à Meticilina , Antibacterianos/uso terapêutico , Carbapenêmicos/uso terapêutico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico , Humanos , Vancomicina/uso terapêuticoRESUMO
BACKGROUND: Because both diarrhea due to other causes and gastrointestinal colonization with toxigenic Clostridioides difficile are common in HSCT, there is a possibility of false-positive diagnoses of C difficile infections (CDI). METHODS: We estimated the probability of a patient being colonized by toxigenic C difficile by testing non-diarrheal surveillance stools from 223 HSCT recipients and the probability that a specimen submitted for C difficile testing was not CDI by determining the number of clinical tests that returned negative from this cohort. The number of expected false-positive CDI was estimated using these probabilities and compared with observed clinical test results. RESULTS: The expected false-positive and the observed numbers of positive clinical results were similar. The 20 patients diagnosed with CDI were also similar to 142 patients with diarrhea and C difficile-negative stools in number of stools on day of testing, associated symptoms, and the recorded number of days to formed stools. C difficile colonization was most commonly detected during the first week and CDI during the second. Retrospective analysis of 837 patients showed that 18 stools were submitted for each diagnosis of CDI. Ribotyping of the surveillance samples showed 17 ribotypes. CONCLUSIONS: Although several assumptions could impact the accuracy of our false-positive CDI estimates, it appears that many HSCT recipients diagnosed with CDI may actually represent colonized status and an alternative cause of diarrhea. Diagnostic stewardship, including limiting CDI diagnoses to patients with positive toxin and restricting stool submissions to patients with more severe symptoms, may decrease the number of false-positive diagnoses.
Assuntos
Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/epidemiologia , Erros de Diagnóstico/estatística & dados numéricos , Fezes/microbiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adulto , Idoso , Clostridioides difficile/classificação , Diarreia/etiologia , Diarreia/microbiologia , Reações Falso-Positivas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ribotipagem , Adulto JovemRESUMO
The low bioavailability of nitric oxide (NO) and its precursor, arginine, contributes to the microvascular pathophysiology of severe falciparum malaria. To better characterize the mechanisms underlying hypoargininemia in severe malaria, we measured the plasma concentrations of amino acids involved in de novo arginine synthesis in children with uncomplicated falciparum malaria (UM; n = 61), children with cerebral falciparum malaria (CM; n = 45), and healthy children (HC; n = 109). We also administered primed infusions of l-arginine uniformly labeled with 13C6 and 15N4 to 8 children with severe falciparum malaria (SM; age range, 4 to 9 years) and 7 healthy children (HC; age range, 4 to 8 years) to measure the metabolic flux of arginine, hypothesizing that arginine flux is increased in SM. Using two different tandem mass spectrometric methods, we measured the isotopic enrichment of arginine in plasma obtained at 0, 60, 90, 120, 150, and 180 min during the infusion. The plasma concentrations of glutamine, glutamate, proline, ornithine, citrulline, and arginine were significantly lower in UM and CM than in HC (P ≤ 0.04 for all pairwise comparisons). Of these, glutamine concentrations were the most markedly decreased: median, 457 µM (interquartile range [IQR], 400 to 508 µM) in HC, 300 µM (IQR, 256 to 365 µM) in UM, and 257 µM (IQR, 195 to 320 µM) in CM. Arginine flux during steady state was not significantly different in SM than in HC by the respective mass spectrometric methods: 93.2 µmol/h/kg of body weight (IQR, 84.4 to 129.3 µmol/h/kg) versus 88.0 µmol/h/kg (IQR, 73.0 to 102.2 µmol/h/kg) (P = 0.247) by the two mass spectrometric methods in SM and 93.7 µmol/h/kg (IQR, 79.1 to 117.8 µmol/h/kg) versus 81.0 µmol/h/kg (IQR, 75.9 to 88.6 µmol/h/kg) (P = 0.165) by the two mass spectrometric methods in HC. A limited supply of amino acid precursors for arginine synthesis likely contributes to the hypoargininemia and NO insufficiency in falciparum malaria in children.
Assuntos
Arginina/sangue , Malária Falciparum/sangue , Plasmodium falciparum/fisiologia , Arginina/química , Criança , Pré-Escolar , Estudos Transversais , Feminino , Glutamina/sangue , Glutamina/química , Humanos , Lactente , Malária Falciparum/parasitologia , MasculinoRESUMO
Recurrent Clostridioides difficile infection (rCDI) may be mediated in part by secondary bile acids. Here we report salvage therapy with ursodeoxycholic acid (UDCA) to prevent rCDI in 16 high-risk patients. Patients on UDCA had a low observed recurrence rate (12.5%). Controlled trials are needed to confirm these observations.
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Antibacterianos/administração & dosagem , Colagogos e Coleréticos/administração & dosagem , Infecções por Clostridium/prevenção & controle , Reposicionamento de Medicamentos , Prevenção Secundária , Ácido Ursodesoxicólico/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Resultado do Tratamento , Adulto JovemRESUMO
We developed a rapid high-throughput PCR test and evaluated highly antibiotic-resistant clinical isolates of Escherichia coli (n = 2,919), Klebsiella pneumoniae (n = 1,974), Proteus mirabilis (n = 1,150), and Pseudomonas aeruginosa (n = 1,484) for several antibiotic resistance genes for comparison with phenotypic resistance across penicillins, cephalosporins, carbapenems, aminoglycosides, trimethoprim-sulfamethoxazole, fluoroquinolones, and macrolides. The isolates originated from hospitals in North America (34%), Europe (23%), Asia (13%), South America (12%), Africa (7%), or Oceania (1%) or were of unknown origin (9%). We developed statistical methods to predict phenotypic resistance from resistance genes for 49 antibiotic-organism combinations, including gentamicin, tobramycin, ciprofloxacin, levofloxacin, trimethoprim-sulfamethoxazole, ertapenem, imipenem, cefazolin, cefepime, cefotaxime, ceftazidime, ceftriaxone, ampicillin, and aztreonam. Average positive predictive values for genotypic prediction of phenotypic resistance were 91% for E. coli, 93% for K. pneumoniae, 87% for P. mirabilis, and 92% for P. aeruginosa across the various antibiotics for this highly resistant cohort of bacterial isolates.
Assuntos
Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos/genética , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/genética , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , África , Ásia , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Europa (Continente) , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , América do Norte , Reação em Cadeia da Polimerase/métodos , América do SulRESUMO
BACKGROUND: More data are needed regarding the incidence, risk factors, and outcomes for Clostridioides difficile infection (CDI) and colonization in patients undergoing an autologous hematopoietic stem cell transplantation (AHSCT). METHODS: We studied 472 consecutive patients admitted for a first AHSCT and conducted a prospective C difficile stool surveillance and ribotyping analysis in a subset of 94 patients. RESULTS: Clostridioides difficile infection was diagnosed in 7% of patients for an incidence of 3.4 CDI/1000 inpatient days, recurrent/reinfection CDI was rare. CDI was increased in patients who were colonized on admission, had required a recent pre-admission inpatient stay for fever and/or serious infection, or received empiric therapy with a carbapenem or extended-spectrum penicillin. CDI was associated with a longer length of stay and higher hospital costs. Twelve of 94 patients (13%) were found to have colonization on admission; CDI was diagnosed in 27% of these vs 1% in those with initial negative stools. Colonization in the hospital for those negative on admission was infrequent. C difficile ribotyping showed a predominance of 014/020. CONCLUSIONS: Clostridioides difficile infection is a significant infection in patients receiving a first AHSCT. The risk factors identified may be useful in designing preventive interventions.
Assuntos
Antibacterianos/uso terapêutico , Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Clostridium/microbiologia , Infecções por Clostridium/patologia , Feminino , Seguimentos , Hospitalização , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Transplante Autólogo , Estados Unidos/epidemiologia , Adulto JovemRESUMO
RATIONALE: A molecular test to distinguish between sepsis and systemic inflammation of noninfectious etiology could potentially have clinical utility. OBJECTIVES: This study evaluated the diagnostic performance of a molecular host response assay (SeptiCyte LAB) designed to distinguish between sepsis and noninfectious systemic inflammation in critically ill adults. METHODS: The study employed a prospective, observational, noninterventional design and recruited a heterogeneous cohort of adult critical care patients from seven sites in the United States (n = 249). An additional group of 198 patients, recruited in the large MARS (Molecular Diagnosis and Risk Stratification of Sepsis) consortium trial in the Netherlands ( www.clinicaltrials.gov identifier NCT01905033), was also tested and analyzed, making a grand total of 447 patients in our study. The performance of SeptiCyte LAB was compared with retrospective physician diagnosis by a panel of three experts. MEASUREMENTS AND MAIN RESULTS: In receiver operating characteristic curve analysis, SeptiCyte LAB had an estimated area under the curve of 0.82-0.89 for discriminating sepsis from noninfectious systemic inflammation. The relative likelihood of sepsis versus noninfectious systemic inflammation was found to increase with increasing test score (range, 0-10). In a forward logistic regression analysis, the diagnostic performance of the assay was improved only marginally when used in combination with other clinical and laboratory variables, including procalcitonin. The performance of the assay was not significantly affected by demographic variables, including age, sex, or race/ethnicity. CONCLUSIONS: SeptiCyte LAB appears to be a promising diagnostic tool to complement physician assessment of infection likelihood in critically ill adult patients with systemic inflammation. Clinical trial registered with www.clinicaltrials.gov (NCT01905033 and NCT02127502).
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Cuidados Críticos/métodos , Unidades de Terapia Intensiva , Sepse/diagnóstico , Teste Bactericida do Soro/métodos , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Adulto , Idoso , Estudos de Coortes , Estado Terminal , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Estudos Prospectivos , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Sepse/sangue , Síndrome de Resposta Inflamatória Sistêmica/sangue , Estados UnidosRESUMO
Background: Studies on the implementation of antibiotic stewardship programs (ASPs) in small hospitals are limited. Accreditation organizations now require all hospitals to have ASPs. Methods: The objective of this cluster-randomized intervention was to assess the effectiveness of implementing ASPs in Intermountain Healthcare's 15 small hospitals. Each hospital was randomized to 1 of 3 ASPs of escalating intensity. Program 1 hospitals were provided basic antibiotic stewardship education and tools, access to an infectious disease hotline, and antibiotic utilization data. Program 2 hospitals received those interventions plus advanced education, audit and feedback for select antibiotics, and locally controlled antibiotic restrictions. Program 3 hospitals received program 2 interventions plus audit and feedback on the majority of antibiotics, and an infectious diseases-trained clinician approved restricted antibiotics and reviewed microbiology results. Changes in total and broad-spectrum antibiotic use within programs (intervention versus baseline) and the difference between programs in the magnitude of change in antibiotic use (eg, program 3 vs 1) were evaluated with mixed models. Results: Program 3 hospitals showed reductions in total (rate ratio, 0.89; confidence interval, .80-.99) and broad-spectrum (0.76; .63-.91) antibiotic use when the intervention period was compared with the baseline period. Program 1 and 2 hospitals did not experience a reduction in antibiotic use. Comparison of the magnitude of effects between programs showed a similar trend favoring program 3, but this was not statistically significant. Conclusions: Only the most intensive ASP intervention was associated with reduction in total and broad-spectrum antibiotic use when compared with baseline. Clinical Trials Registration: NCT03245879.
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Antibacterianos/uso terapêutico , Gestão de Antimicrobianos/organização & administração , Implementação de Plano de Saúde , Hospitais Comunitários , Instituições de Assistência Ambulatorial , Análise por Conglomerados , Idaho , UtahRESUMO
During August 2017, two separate clusters of platelet transfusion-associated bacterial sepsis were reported in Utah and California. In Utah, two patients died after platelet transfusions from the same donation. Clostridium perfringens isolates from one patient's blood, the other patient's platelet bag, and donor skin swabs were highly related by whole genome sequencing (WGS). In California, one patient died after platelet transfusion; Klebsiella pneumoniae isolates from the patient's blood and platelet bag residuals and a nontransfused platelet unit were matched using WGS. Investigation revealed no deviations in blood supplier or hospital procedures. Findings in this report highlight that even when following current procedures, the risk for transfusion-related infection and fatality persists, making additional interventions necessary. Clinicians need to be vigilant in monitoring for platelet-transmitted bacterial infections and report adverse reactions to blood suppliers and hemovigilance systems. Blood suppliers and hospitals could consider additional evidence-based bacterial contamination risk mitigation strategies, including pathogen inactivation, rapid detection devices, and modified screening of bacterial culture protocols.
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Plaquetas/microbiologia , Transfusão de Plaquetas/efeitos adversos , Sepse/etiologia , California , Análise por Conglomerados , Evolução Fatal , Feminino , Humanos , Masculino , UtahRESUMO
The association between pre-hematopoietic stem cell transplantation (HSCT) vancomycin-resistant Enterococcus (VRE) colonization, HSCT-associated VRE bacteremia, and HSCT mortality is disputed. We studied 161 consecutive patients with acute leukemia who underwent HSCT at our hospital between 2006 and 2014, of whom 109 also received leukemia induction/consolidation on our unit. All inpatients had weekly VRE stool surveillance. Pre-HSCT colonization was not associated with increases in HSCT mortality but did identify a subgroup of HSCT recipients with a higher risk for VRE bacteremia and possibly bacteremia from other organisms. The major risk factor for pre-HSCT colonization was the number of hospital inpatient days between initial admission for leukemia and HSCT. One-third of evaluable patients colonized before HSCT were VRE-culture negative on admission for HSCT; these patients had an increased risk for subsequent VRE stool surveillance positivity but not VRE bacteremia. Molecular typing of VRE isolates obtained before and after HSCT showed that VRE strains frequently change. Postengraftment VRE bacteremia was associated with a much higher mortality than pre-engraftment VRE bacteremia. Pre-engraftment bacteremia from any organism was associated with an alternative donor and resulted in an increase in hospital length of stay and cost. Mortality was similar for pre-engraftment VRE bacteremia and pre-engraftment bacteremia due to other organisms, but mortality associated with post-engraftment VRE bacteremia was higher and largely explained by associated severe graft-versus-host disease and relapsed leukemia. These data emphasize the importance of distinguishing between VRE colonization before HSCT and at HSCT, between pre-engraftment and postengraftment VRE bacteremia, and between VRE bacteremia and bacteremia from other organisms.
Assuntos
Bacteriemia/microbiologia , Enterococcus/isolamento & purificação , Infecções por Bactérias Gram-Positivas/microbiologia , Transplante de Células-Tronco Hematopoéticas , Resistência a Vancomicina , Adolescente , Adulto , Idoso , Antibioticoprofilaxia , Bacteriemia/tratamento farmacológico , Bacteriemia/etiologia , Comorbidade , Custos e Análise de Custo , Enterococcus/efeitos dos fármacos , Fezes/microbiologia , Feminino , Seguimentos , Microbioma Gastrointestinal , Doença Enxerto-Hospedeiro/etiologia , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/economia , Infecções por Bactérias Gram-Positivas/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/economia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Hospedeiro Imunocomprometido , Leucemia/terapia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
Decreased bioavailability of nitric oxide (NO) is a major contributor to the pathophysiology of severe falciparum malaria. Tetrahydrobiopterin (BH4) is an enzyme cofactor required for NO synthesis from L-arginine. We hypothesized that systemic levels of BH4 would be decreased in children with cerebral malaria, contributing to low NO bioavailability. In an observational study in Tanzania, we measured urine levels of biopterin in its various redox states (fully reduced [BH4] and the oxidized metabolites, dihydrobiopterin [BH2] and biopterin [B0]) in children with uncomplicated malaria (UM, n = 55), cerebral malaria (CM, n = 45), non-malaria central nervous system conditions (NMC, n = 48), and in 111 healthy controls (HC). Median urine BH4 concentration in CM (1.10 [IQR:0.55-2.18] µmol/mmol creatinine) was significantly lower compared to each of the other three groups - UM (2.10 [IQR:1.32-3.14];p<0.001), NMC (1.52 [IQR:1.01-2.71];p = 0.002), and HC (1.60 [IQR:1.15-2.23];p = 0.005). Oxidized biopterins were increased, and the BH4:BH2 ratio markedly decreased in CM. In a multivariate logistic regression model, each Log10-unit decrease in urine BH4 was independently associated with a 3.85-fold (95% CI:1.89-7.61) increase in odds of CM (p<0.001). Low systemic BH4 levels and increased oxidized biopterins contribute to the low NO bioavailability observed in CM. Adjunctive therapy to regenerate BH4 may have a role in improving NO bioavailability and microvascular perfusion in severe falciparum malaria.
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Biopterinas/análogos & derivados , Malária Cerebral/urina , Malária Falciparum/urina , Biopterinas/urina , Pré-Escolar , Feminino , Humanos , Masculino , Óxido Nítrico/metabolismo , Oxirredução , Estudos RetrospectivosRESUMO
Antibiotics have been shown to influence the risk of infection with specific Clostridium difficile strains as well as the risk of C. difficile infection (CDI). We performed a retrospective case-control study of patients infected with the epidemic BI/NAP1/027 strain in a U.S. hospital following recognition of increased CDI severity and culture of stools positive by C. difficile toxin immunoassay. Between 2005 and 2007, 72% (103/143) of patients with first-episode CDIs were infected with the BI strain by restriction endonuclease analysis (REA) typing. Most patients received multiple antibiotics within 6 weeks of CDI onset (median of 3 antibiotic classes). By multivariate analysis, fluoroquinolone and macrolide exposure was more frequent among BI cases than among non-BI-infected controls (odds ratio [OR] for fluoroquinolones, 3.2; 95% confidence interval [CI], 1.3 to 7.5; (P < 0.001; OR for macrolides, 5.2; 95% CI, 1.1 to 24.0; P = 0.04)). In contrast, clindamycin use was less frequent among the BI cases than among the controls (OR, 0.1; 95% CI, 0.03 to 0.4; P = 0.001). High-level resistance to moxifloxacin and azithromycin was more frequent among BI strains (moxifloxacin, 49/102 [48%] BI versus 0/40 non-BI, P = 0.0001; azithromycin, 100/102 [98%] BI versus 22/40 [55%] non-BI, P = 0.0001). High-level resistance to clindamycin was more frequent among non-BI strains (22/40 [55%] non-BI versus 7/102 [7%] BI, P = 0.0001). Fluoroquinolone use, macrolide use, and C. difficile resistance to these antibiotic classes were associated with infection by the epidemic BI strain of C. difficile in a U.S. hospital during a time when CDI rates were increasing nationally due to the highly fluoroquinolone-resistant BI/NAP1/027 strain.
Assuntos
Antibacterianos/efeitos adversos , DNA Bacteriano/genética , Enterocolite Pseudomembranosa/etiologia , Fluoroquinolonas/efeitos adversos , Macrolídeos/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Toxinas Bacterianas/imunologia , Toxinas Bacterianas/isolamento & purificação , Estudos de Casos e Controles , Clostridioides difficile/efeitos dos fármacos , Clostridioides difficile/genética , Clostridioides difficile/patogenicidade , Farmacorresistência Bacteriana Múltipla , Enterocolite Pseudomembranosa/tratamento farmacológico , Enterocolite Pseudomembranosa/microbiologia , Enterocolite Pseudomembranosa/mortalidade , Enterotoxinas/imunologia , Enterotoxinas/isolamento & purificação , Fezes/microbiologia , Feminino , Fluoroquinolonas/administração & dosagem , Humanos , Macrolídeos/administração & dosagem , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Proibitinas , Estudos Retrospectivos , Análise de Sobrevida , Estados UnidosRESUMO
Recent outbreaks of carbapenem-resistant Enterobacteriaceae infections associated with duodenoscopes used for endoscopic retrograde cholangiopancreatography have highlighted the challenge of cleaning and high-level disinfection of these instruments. The Food and Drug Administration has suggested that duodenoscope surveillance by microbiological culturing, along with strict adherence to reprocessing protocols, may help reduce the risk of duodenoscope-associated infection transmission. We developed and validated an effective, user-friendly duodenoscope sampling and culture protocol and compared its performance to the interim Centers for Disease Control and Prevention-recommended guidelines. Our protocol resulted in a 65% recovery rate for Gram-negative organisms, demonstrating a 2-fold increased recovery rate compared to the CDC method. The implementation of this protocol may increase the feasibility of duodenoscope surveillance for microbiology laboratories and endoscopy departments.
Assuntos
Técnicas Bacteriológicas/métodos , Duodenoscópios/microbiologia , Colangiopancreatografia Retrógrada Endoscópica/métodos , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/transmissão , HumanosRESUMO
Bloodstream infection is a serious condition associated with significant morbidity and mortality. The outcome of these infections can be positively affected by the early implementation of effective antibiotic therapy based on the identification of the infecting organism and genetic markers associated with antibiotic resistance. In this study, we evaluated the microarray-based Verigene Gram-negative blood culture (BC-GN) assay in the identification of 8 genus or species targets and 6 genetic resistance determinants in positive blood culture broths. A total of 1,847 blood cultures containing Gram-negative organisms were tested using the BC-GN assay. This comprised 729 prospective fresh, 781 prospective or retrospective frozen, and 337 simulated cultures representing 7 types of aerobic culture media. The results were compared to those with standard bacterial culture and biochemical identification with nucleic acid sequence confirmation of the resistance determinants. Among monomicrobial cultures, the positive percent agreement (PPA) of the BC-GN assay with the reference method was as follows; Escherichia coli, 100%; Klebsiella pneumoniae, 92.9%; Klebsiella oxytoca, 95.5%; Enterobacter spp., 99.3%; Pseudomonas aeruginosa, 98.9%; Proteus spp., 100%; Acinetobacter spp., 98.4%; and Citrobacter spp., 100%. All organism identification targets demonstrated >99.5% negative percent agreement (NPA) with the reference method. Of note, 25/26 cultures containing K. pneumoniae that were reported as not detected by the BC-GN assay were subsequently identified as Klebsiella variicola. The PPA for identification of resistance determinants was as follows; blaCTX-M, 98.9%; blaKPC, 100%; blaNDM, 96.2%; blaOXA, 94.3%; blaVIM, 100%; and blaIMP, 100%. All resistance determinant targets demonstrated >99.9% NPA. Among polymicrobial specimens, the BC-GN assay correctly identified at least one organism in 95.4% of the broths and correctly identified all organisms present in 54.5% of the broths. The sample-to-result processing and automated reading of the detection microarray results enables results within 2 h of culture positivity.
Assuntos
Bacteriemia/diagnóstico , Farmacorresistência Bacteriana , Bactérias Gram-Negativas/genética , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Bacteriemia/microbiologia , Técnicas Bacteriológicas/métodos , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Análise em Microsséries/métodos , Estudos Prospectivos , Estudos Retrospectivos , Fatores de TempoRESUMO
Multiplexed gastrointestinal PCR panels (MGPPs) are frequently used to aid the diagnosis and management of diarrhea in hematopoietic stem cell transplantation (HCT) recipients. Many issues related to the optimal use of MGPPs in HCT patients remain to be clarified. We aimed to better define MGPP diagnostic and therapeutic stewardship in HCT recipients, including indications for and benefits of testing, optimal timing of tests, and interpretation of results. We retrieved 463 consecutive MGPPs ordered on 651 consecutive first HCT (312 allogeneic, 339 autologous) performed at our institution between June 2015 and June 2023. One hundred and sixteen of the 463 MGPPs (25%) identified at least 1 diarrheagenic pathogen, and 12 (3%) identified more than 1 diarrheagenic pathogen. A positive result was more likely if the test was ordered within 48 hours of a hospital admission (41%; 32 of 78) or as an outpatient (41%; 46 of 111) compared with evaluation of hospital-onset diarrhea (14%; 38 of 274). Among the positive results, the most frequent pathogens identified included Clostridioides difficile (64%), diarrheagenic Escherichia coli (20%), norovirus (9%), and adenovirus 40/41 (5%). Thirty-eight percent of the positive C. difficile MGPP determinations were associated with a positive test for toxin. In our allogeneic HCT cohort, 3% of MGPPs for hospital-onset diarrhea yielded an organism other than C. difficile. Fifty-six percent of positive and 14% of all submitted tests resulted in a change in treatment. For organisms other than C. difficile, only 1% of all tests and 5% of positive tests resulted in initiation of therapy. For patients at risk for acute graft-versus-host disease (aGVHD), a positive or negative MGPP result was not predictive of a new diagnosis of aGVHD in proximity to diarrhea onset. These results suggest that MGPP testing is most useful when performed at hospital admission or on an outpatient basis. Because MGPPs are sensitive and do not distinguish between colonization and causes of diarrhea, caution is needed when interpreting results, especially for toxin-negative C. difficile and diarrheagenic gram-negative organisms.
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Diarreia , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Diarreia/diagnóstico , Diarreia/microbiologia , Diarreia/etiologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Clostridioides difficile/isolamento & purificação , Reação em Cadeia da Polimerase Multiplex/métodos , Idoso , Adolescente , Adulto Jovem , Estudos RetrospectivosRESUMO
Background: Disordered amino acid metabolism is observed in cerebral malaria (CM). We sought to determine whether abnormal amino acid concentrations were associated with level of consciousness in children recovering from coma. We quantified 21 amino acids and coma scores longitudinally and analyzed data for associations. Methods: In a prospective observational study, we enrolled 42 children with CM. We measured amino acid levels at entry and at frequent intervals thereafter and assessed consciousness by Blantyre Coma Scores (BCS). Thirty-six healthy children served as controls for in-country normal amino acid ranges. We employed logistic regression using a generalized linear mixed-effects model to assess associations between out-of-range amino acid levels and BCS. Results: At entry 16/21 amino acid levels were out-of-range. Longitudinal analysis revealed 10/21 out-of-range amino acids were significantly associated with BCS. Elevated phenylalanine levels showed the highest association with low BCS. This finding held when out-of-normal-range data were analyzed at each sampling time. Discussion: We provide longitudinal data for associations between abnormal amino acid levels and recovery from CM. Of 10 amino acids significantly associated with BCS, we propose that elevated phenylalanine may be a surrogate for impaired clearance of ether lipid mediators of inflammation contributing to CM pathogenesis.
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(1) Background: SeptiCyte RAPID is a molecular test for discriminating sepsis from non-infectious systemic inflammation, and for estimating sepsis probabilities. The objective of this study was the clinical validation of SeptiCyte RAPID, based on testing retrospectively banked and prospectively collected patient samples. (2) Methods: The cartridge-based SeptiCyte RAPID test accepts a PAXgene blood RNA sample and provides sample-to-answer processing in ~1 h. The test output (SeptiScore, range 0-15) falls into four interpretation bands, with higher scores indicating higher probabilities of sepsis. Retrospective (N = 356) and prospective (N = 63) samples were tested from adult patients in ICU who either had the systemic inflammatory response syndrome (SIRS), or were suspected of having/diagnosed with sepsis. Patients were clinically evaluated by a panel of three expert physicians blinded to the SeptiCyte test results. Results were interpreted under either the Sepsis-2 or Sepsis-3 framework. (3) Results: Under the Sepsis-2 framework, SeptiCyte RAPID performance for the combined retrospective and prospective cohorts had Areas Under the ROC Curve (AUCs) ranging from 0.82 to 0.85, a negative predictive value of 0.91 (sensitivity 0.94) for SeptiScore Band 1 (score range 0.1-5.0; lowest risk of sepsis), and a positive predictive value of 0.81 (specificity 0.90) for SeptiScore Band 4 (score range 7.4-15; highest risk of sepsis). Performance estimates for the prospective cohort ranged from AUC 0.86-0.95. For physician-adjudicated sepsis cases that were blood culture (+) or blood, urine culture (+)(+), 43/48 (90%) of SeptiCyte scores fell in Bands 3 or 4. In multivariable analysis with up to 14 additional clinical variables, SeptiScore was the most important variable for sepsis diagnosis. A comparable performance was obtained for the majority of patients reanalyzed under the Sepsis-3 definition, although a subgroup of 16 patients was identified that was called septic under Sepsis-2 but not under Sepsis-3. (4) Conclusions: This study validates SeptiCyte RAPID for estimating sepsis probability, under both the Sepsis-2 and Sepsis-3 frameworks, for hospitalized patients on their first day of ICU admission.
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BACKGROUND: Current information is limited on the incidence, risk factors, and consequences of extended-spectrum cephalosporin resistant Enterobacteriaceae (ESCRE) carriage in patients undergoing therapy for newly-diagnosed acute leukemia. METHODS: We monitored 300 consecutive patients who submitted a first stool within the first week of initial hospitalization for initial and hospital acquired ESCRE carriage. Selected available isolates underwent DNA sequencing for determination of strain typing and resistance genes. RESULTS: 19 (6%) patients had ESCRE in their initial stool, and there was continued risk for new acquisition throughout their multiple hospitalizations. Patients with AML had more acquired carriage during their initial hospitalization. Increased hospitalizations and male sex were risk factors for detected acquired ESCRE carriage. ESCRE stool carriage was predictive for ESCRE BSI but not for overall survival. Sequencing revealed that E. coli ESCRE isolates contained primarily ESBL, while Enterobacter spp. and Citrobacter spp. showed primarily AmpC genes. The antibiotic sensitivity patterns for ESCRE BSI isolates reflected these genome findings. DISCUSSION/CONCLUSIONS: ESCRE carriage is common in patients with acute leukemia undergoing repeated hospitalizations and increases the risk for ESCRE BSI. ESCRE genera express differing resistance genes which may be predictive for empiric antibiotic efficacy.