Clinical Impact of the Cefazolin Inoculum Effect
头孢唑啉接种效果的临床影响
基本信息
- 批准号:10735541
- 负责人:
- 金额:$ 68.77万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-06-05 至 2028-05-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAdverse reactionsAffectAntibioticsAttentionAustraliaBacteremiaBiologicalBlood CirculationCanadaCefazolinCephalosporinsChildChileClinicalClinical DataClinical MicrobiologyColombiaDataDetectionEarly DiagnosisEffectivenessEnrollmentFailureFloxacillinGenerationsGenomicsGenus staphylococcusGeographic LocationsGoalsHepatotoxicityInfectionInterstitial NephritisIsraelLaboratoriesLatin AmericaLifeMediatorMethicillinMethodist ChurchMinimum Inhibitory Concentration measurementNafcillinNatureNeutropeniaNew ZealandOsteomyelitisOutcomeOxacillinPatient-Focused OutcomesPatientsPenicillinsPerformancePharmaceutical PreparationsPhenotypePredispositionPrevalenceProductionPublishingRandomizedReactionRestRetrospective StudiesRiskRisk FactorsSafetySample SizeSensitivity and SpecificitySepsisSingaporeSpecific qualifier valueStaphylococcus aureusStaphylococcus aureus infectionTest ResultTestingTherapeuticUnited KingdomUnited Statesarmbeta-Lactamasebeta-Lactamsclinically relevantcostdiagnostic tooleffectiveness evaluationhigh riskhuman pathogeninsightmethicillin resistant Staphylococcus aureusminimal inhibitory concentrationmortalitynitrocefinnovelnovel diagnosticsopen labelparticipant enrollmentpathogenprimary outcomepublic health relevancerapid detectionrapid testrecruitsecondary outcomesuccesstreatment optimization
项目摘要
ABSTRACT
Staphylococcus aureus is a major human pathogen responsible for a wide range of life-threatening infections.
Many of these infections are caused by methicillin-susceptible S. aureus (MSSA). MSSA represent a major
burden among S. aureus infections and are important contributors to mortality. For decades, the first line of
therapy for severe MSSA infections have been the isoxazolyl-penicillins (ISP, e.g., nafcillin). However, recent
data suggest that clinical outcomes in MSSA bacteremia are similar in patients treated with cefazolin (vs
nafcillin), a cephalosporin with activity against MSSA that appears to be less toxic. Indeed, treatment with nafcillin
seems to be associated with increased costs, more drug reactions (including hepatotoxicity, interstitial nephritis
and neutropenia) and, possibly, higher mortality. Due to these concerns, an important shift in the treatment of
MSSA is occurring whereby clinicians are now using cefazolin as first line of therapy for severe MSSA
infections. An important concern of using cefazolin and other cephalosporins as primary therapy for these serious
infections is the cefazolin inoculum effect (CzIE), defined as a cefazolin minimal inhibitory concentration of >
16 µg/ml when a high inoculum (107 CFU/ml) is used. The CzIE has been associated with failures in the treatment
of deep-seated MSSA infections and with the production of certain isotypes of the staphylococcal β-lactamase.
However, the characterization of the clinical impact of this phenomenon in deep-seated MSSA infections
is limited. In addition, it is currently not possible to detect the CzIE in a standard clinical microbiology laboratory
given the cumbersome and expensive nature of the gold standard test for its detection. Our published and
preliminary clinical data suggest that the CzIE is an important contributor to worse clinical outcomes of severe
MSSA infections. Furthermore, we have developed and published a novel colorimetric nitrocefin-based rapid test
(~3 h) that detects the CzIE with high sensitivity and specificity that can be incorporated in the routine clinical
microbiology laboratory. We postulate that, i) the CzIE negatively impacts clinical outcomes in MSSA bacteremia
treated with cefazolin and, ii) a rapid test can be readily implemented for the identification of the CzIE in S.
aureus bacteremia and can detect patients at higher risk of poor outcomes. In order to address these hypotheses,
we will take advantage of the Staphylococcus aureus Network Adaptive Platform (SNAP) trial, a multicenter,
pragmatic, multi-arm, open-label adaptive platform trial addressing multiple therapeutic questions in patients with
S. aureus bacteremia. We will focus in the MSSA “domain” that evaluates the effectiveness and safety of
cefazolin vs ISP in a randomized fashion, currently enrolling in Australia, Singapore, Canada, Israel, New
Zealand, United Kingdom, United States, Colombia and Chile. The specific aims of our proposal are: i) to define
the clinical impact of the CzIE in MSSA bacteremia and, ii) to determine the clinical value and feasibility of a
rapid test to detect the CzIE. Our findings are likely to transform the treatment approach for MSSA infections and
will provide the basis to develop novel diagnostic tools to the management of MSSA infections.
摘要
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Cesar Augusto Arias其他文献
Cesar Augusto Arias的其他文献
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{{ truncateString('Cesar Augusto Arias', 18)}}的其他基金
The LiaFSR system and antimicrobial peptide resistance in enterococci
LiaFSR 系统和肠球菌抗菌肽耐药性
- 批准号:
10553808 - 财政年份:2022
- 资助金额:
$ 68.77万 - 项目类别:
Dynamics of Colonization and Infection by Multidrug-resistant Pathogens in Immunocompromised and Critically Ill Patients (DYNAMITE)
免疫功能低下和危重患者中多重耐药病原体定植和感染的动态 (DYNAMITE)
- 批准号:
10226283 - 财政年份:2020
- 资助金额:
$ 68.77万 - 项目类别:
Dynamics of Colonization and Infection by Multidrug-resistant Pathogens in Immunocompromised and Critically Ill Patients (DYNAMITE)
免疫功能低下和危重患者中多重耐药病原体定植和感染的动态 (DYNAMITE)
- 批准号:
10614690 - 财政年份:2020
- 资助金额:
$ 68.77万 - 项目类别:
VENOUS: A translational study of enterococcal bacteremia
静脉:肠球菌菌血症的转化研究
- 批准号:
10624439 - 财政年份:2020
- 资助金额:
$ 68.77万 - 项目类别:
Project 1: Genomics of Pathobionts and Transition From Colonization to Infection
项目 1:病原体基因组学和从定植到感染的转变
- 批准号:
10226287 - 财政年份:2020
- 资助金额:
$ 68.77万 - 项目类别:
Dynamics of Colonization and Infection by Multidrug-resistant Pathogens in Immunocompromised and Critically Ill Patients (DYNAMITE)
免疫功能低下和危重患者中多重耐药病原体定植和感染的动态 (DYNAMITE)
- 批准号:
10024956 - 财政年份:2020
- 资助金额:
$ 68.77万 - 项目类别:
VENOUS: A translational study of enterococcal bacteremia
静脉:肠球菌菌血症的转化研究
- 批准号:
10593508 - 财政年份:2020
- 资助金额:
$ 68.77万 - 项目类别:
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