Impact of rapid polymerase chain reaction results on management of pediatric patients with enteroviral meningitis

Robinson, Christine C.; Willis, Mary Alissa; Meagher, Ashley D.; Gieseker, Karen E.; Rotbart, Harley A.; Glodé, Mary P.

doi:10.1097/00006454-200204000-00005

Cited by 119 publications

(100 citation statements)

References 13 publications

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“…The analysis comparing clinical data for patients whose positive EV-PCR results were available within 24 hr and those whose results were available >24 hr after CSF collection showed a positive correlation between the TAT and the duration of antibiotic treatment. However, as observed previously [Robinson et al, 2002], there was no statistically significant difference in the length of stay. A comparison of the clinical data of patients admitted over the weekend and of those admitted during the week showed that the length of stay was one day shorter (P ¼ 0.02) and the use of antibiotics lower when EV-PCR was performed daily.…”

Section: Discussionsupporting

confidence: 79%

“…This assay is an effective alternative to viral culture, since it can provide rapid results within 5-24 hr of receipt of the sample [Ramers et al, 2000;Stellrecht et al, 2002;Archimbaud et al, 2004]. Previous studies of children suggested that the use of the enterovirus PCR assay has a clinical benefit by reducing antibiotic or antiviral therapy, and avoiding ancillary tests, and also it reduces hospital related costs allowing earlier discharge [Hamilton et al, 1999;Ramers et al, 2000;Robinson et al, 2002;Stellrecht et al, 2002]. Children are the primary victims of enterovirus meningitis, but the illness is not uncommon in adults [Rotbart et al, 1998;Peigue-Lafeuille et al, 2002].…”

Section: Introductionmentioning

confidence: 99%

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Impact of rapid enterovirus molecular diagnosis on the management of infants, children, and adults with aseptic meningitis

Archimbaud

Chambon

Bailly

et al. 2008

Journal of Medical Virology

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Enteroviruses (EV) are the main etiological agents of aseptic meningitis. Diagnosis is made by detecting the genome using RT-PCR. The aim of the study was to evaluate the impact of a positive diagnosis on the management of infants, children, and adults. During 2005, 442 patients were admitted to hospital with suspected meningitis. Clinical and laboratory data and initial treatment were recorded for all patients with enteroviral meningitis. The turnaround time of tests and the length of hospital stay were analyzed. The results showed that EV-PCR detected EV in 69 patients (16%), 23% (16/69) were adults. About 18% of CSF samples had no pleocytosis. After positive PCR results, 63% of children were discharged immediately (mean 2 hr 30 min) and 95% within 24 hr. Infants and adults were discharged later (after 1.8 and 2 days, respectively). The use of antibiotics was significantly lower in children than in infants and adults. The PCR results allowed discontinuation of antibiotics in 50-60% of all patients treated. Patients received acyclovir in 16% of cases (7% children vs. 50% adults) and 23% (11% vs. 69%) underwent a CT scan. Clinical data were compared between patients whose positive EV-PCR results were available within 24 hr (n ¼ 32) and those whose results were available > 24 hr after collection of CSF (n ¼ 14). Duration of antibiotic treatment (difference: 2.3 days; P ¼ 0.05) was reduced between the two groups. No statistical difference in the length of stay was observed. The EV-PCR assay should be performed daily in hospital laboratory practice and considered as part of the initial management of meningitis.

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Impact of rapid enterovirus molecular diagnosis on the management of infants, children, and adults with aseptic meningitis

Archimbaud

Chambon

Bailly

et al. 2008

Journal of Medical Virology

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“…Enteroviruses are the most common cause of aseptic meningitis in both children and adults and may cause up to 90% of cases of aseptic meningitis for which an etiology is identified (1,14,18,19). The rapid detection and the rapid characterization of enteroviral meningitis are essential for making decisions for patient management and treatment (5,15,17,20). The provision of enterovirus test results on a daily basis can have a substantial impact on health care and has been shown to be highly cost-effective (9,12,17).…”

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confidence: 99%

GeneXpert Enterovirus Assay: One-Year Experience in a Routine Laboratory Setting and Evaluation on Three Proficiency Panels

et al. 2008

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A prospective unblinded comparative evaluation of three assays for the detection of enteroviral RNA performed on 83 positive and 79 negative cerebrospinal fluid samples showed initial and resolved sensitivities of 90.4% and 98.8%, respectively, for the Cepheid GeneXpert enterovirus assay; 94.0% and 97.6%, respectively, for the Argene enterovirus consensus kit; and 100% and 100%, respectively, for an in-house real-time PCR. The initial and resolved specificities were 100% for all three assays.Enteroviruses comprise a large group of immunologically distinct serotypes of viruses belonging to the family Picornaviridae (18). Infection with enteroviruses is associated with protean clinical manifestations, ranging from asymptomatic or mild febrile illness to severe and potentially fatal syndromes, including paralysis, aseptic meningitis, encephalitis, myocarditis, and neonatal systemic infection (1). Enteroviruses are the most common cause of aseptic meningitis in both children and adults and may cause up to 90% of cases of aseptic meningitis for which an etiology is identified (1,14,18,19). The rapid detection and the rapid characterization of enteroviral meningitis are essential for making decisions for patient management and treatment (5,15,17,20). The provision of enterovirus test results on a daily basis can have a substantial impact on health care and has been shown to be highly cost-effective (9,12,17). Since the conventional means of diagnosis of enteroviral meningitis by cell culture from cerebrospinal fluid (CSF) is timeconsuming and expensive and lacks sensitivity, some commercial and several in-house PCR protocols as well as nucleic acid sequence-based amplification assays have been developed during the last 15 years in order to improve the ability to detect enterovirus from CSF (2-4, 6, 7, 11, 13, 16, 20-22, 24-26). The most widely used PCR-based assays for the routine diagnosis of enteroviral meningitis are those that detect PCR products in microtiter wells (6,21,22) and those that use the real-time PCR technology (2,3,13,(24)(25)(26). However, all of these approaches require specially trained laboratory staff, thus limiting the ability of the "real-time" technology to deliver patient results that would be most useful for making patient management decisions STAT.The latest development in the field of the molecular diagnosis of enteroviral meningitis is a fully automated real-time multiplex, reverse transcription-PCR assay, the GeneXpert enterovirus assay (GXEA; Cepheid, Sunnyvale, CA) (10). GXEA is, at present, the only FDA-approved assay for the qualitative detection of enterovirus RNA in CSF. It combines automated nucleic acid sample preparation, amplification, and real-time detection of enteroviral RNA in a disposable, macro/microfluidic cartridge using the GeneXpert Dx system instrument. To date, only one evaluation of GXEA has been published in peer-reviewed journals. A multicenter beta trial with 102 CSF samples obtained from patients with suspected meningitis (34 of whom were enterovirus positive) ...

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“…Several other groups have analyzed the clinical impact of real-time PCR testing for CSF enterovirus. Projected direct variable cost savings were achieved by earlier discharge of patients and decreased use of antibiotics, [11][12][13] although some of the cost reductions depend on the prevalence of enterovirus meningitis exceeding a certain threshold. 13 In conclusion, we developed a real-time PCR for HSV using the Cepheid SmartCycler with sensitivity comparable to that of national reference laboratories using LightCycler.…”

Section: Discussionmentioning

confidence: 99%

Real-Time Polymerase Chain Reaction Detection of Herpes Simplex Virus in Cerebrospinal Fluid and Cost Savings from Earlier Hospital Discharge

Rand

Houck

Lawrence

2005

The Journal of Molecular Diagnostics

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Neonatal herpes simplex virus (HSV) can be a devastating illness and may be difficult to diagnose in those cases without a typical skin rash. As a result, physicians often rely on HSV polymerase chain reaction of cerebrospinal fluid to rule out HSV encephalitis. We developed a real-time polymerase chain reaction assay for HSV using the SmartCycler II (Cepheid, Sunnyvale, CA). End point dilution studies showed sensitivity comparable to that of two national reference laboratories that use LightCycler. In-house turnaround time was Ϸ1.5 days versus Ϸ5.2 days for sending the test to a reference laboratory. We hypothesized that the rapid availability of a negative test result would allow physicians to discharge appropriate patients earlier. Six months after implementation, clinical case analysis identified 12 pediatric patients who were discharged earlier based on more rapid test results, with a projected savings of Ϸ55.2 hospital days throughout the first year. Actual length of stay for patients tested in-house was significantly less than that of historical controls and was projected to save Ϸ70.2 hospital days in the first year. Including projected annual laboratory cost/test savings of Ϸ$11,000, a total savings of $38,000 to $43,000 was estimated for the first year of implementation, more than offsetting startup instrument and development cost. (J Mol Diagn 2005, 7:511-516) Neonatal herpes simplex virus (HSV) infection is a life threatening infection occurring within the first several weeks after birth. Classically, ϳ60 to 70% of patients have a typical herpetic skin rash, with or without disseminated infection involving brain, liver, lung, and other organs.1 Because central nervous system HSV can present with seizures, low-grade fever, and other nonspecific symptoms in the absence of the vesicular skin rash, physicians often rely on a negative cerebrospinal fluid (CSF) HSV polymerase chain reaction (PCR) to rule out HSV encephalitis.2-4 In our hospital HSV CSF PCR was sent to a reference laboratory with an average 5.2-day turnaround time. We attempted to show that performing HSV CSF PCR in the hospital laboratory would shorten this turnaround time and lead to an earlier discharge for a subset of neonates without other complications who were kept in the hospital for observation pending this test result.

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Impact of rapid polymerase chain reaction results on management of pediatric patients with enteroviral meningitis

Abstract: Rapid reporting of PCR results can have a significant impact on several outcome measures for patients with EV meningitis.

Cited by 119 publications

References 13 publications

Impact of rapid enterovirus molecular diagnosis on the management of infants, children, and adults with aseptic meningitis

Impact of rapid enterovirus molecular diagnosis on the management of infants, children, and adults with aseptic meningitis

GeneXpert Enterovirus Assay: One-Year Experience in a Routine Laboratory Setting and Evaluation on Three Proficiency Panels

Real-Time Polymerase Chain Reaction Detection of Herpes Simplex Virus in Cerebrospinal Fluid and Cost Savings from Earlier Hospital Discharge

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