The impact of an enteroviral RT-PCR assay on the diagnosis of aseptic meningitis and patient management

Stellrecht, Kathleen A.; Harding, Ian; Woron, Amy M.; Lepow, Martha L.; Venezia, Richard A.

doi:10.1016/s1386-6532(02)00030-6

Cited by 80 publications

(80 citation statements)

References 16 publications

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“…This molecular assay was used daily in the virology laboratory for infants, children and adults. Previous studies [Hamilton et al, 1999;Ramers et al, 2000;Stellrecht et al, 2002] demonstrated a significantly shorter length of stay and duration of antibiotic use for patients with positive EV-PCR results than those with negative results. However, the use of negative EV-PCR results as controls is not necessarily a wise choice.…”

Section: Discussionmentioning

confidence: 96%

“…For diagnosis, the ''gold standard'' for enterovirus meningitis is the detection of enterovirus genome by reverse transcriptase-polymerase chain reaction (RT-PCR) from cerebrospinal fluid (CSF) specimens. 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].…”

Section: Introductionmentioning

confidence: 99%

“…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: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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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“…Prompt diagnosis of herpes simplex virus encephalitis is especially important because treatment with intravenous acyclovir decreases morbidity and mortality (17). Furthermore, a rapid diagnosis of enteroviral meningitis can facilitate early discharge from the hospital and prevent unnecessary antibiotic treatment and further laboratory testing (10,14). The majority of viral PCR tests performed on CSF, however, yield negative results, and the etiology of aseptic meningoencephalitis remains unknown Ͼ50% of the time (3,8).…”

Section: Discussionmentioning

confidence: 99%

Validation of Laboratory Screening Criteria for Herpes Simplex Virus Testing of Cerebrospinal Fluid

et al. 2007

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Most patients with herpes simplex virus (HSV) central nervous system (CNS) infection have abnormalcerebrospinal fluid (CSF) indices. Therefore, we implemented screening criteria based on CSF values and host immune status to guide testing. All CSF samples submitted for HSV PCR analysis from January 1999 through December 2004 were included in the study. Specimens from patients with human immunodeficiency virus, a history of transplants, an age of <2 years, a CSF white blood cell count of >5 cells/mm 3 , or a protein level of >50 mg/dl were tested upon request. All other samples were rejected and frozen. To validate our screening criteria, rejected specimens were pooled and tested retrospectively. Electronic medical records were also reviewed. A total of 1,659 HSV PCR requests from 1,458 patients were screened. Of the 1,296 specimens (78.1%) accepted for testing, 1,213 were negative, 7 were positive for HSV type 1 (HSV-1), 26 were positive for HSV-2, and 50 had unavailable results. Sixteen requests were rejected because an alternative microbiologic diagnosis had been established. Of the 347 samples rejected based on criteria, 222 (64.0%) remained available for pooled testing. No HSV-1-positive samples were identified in the rejected specimens. Two rejected specimens tested positive for HSV-2 DNA, but both met acceptance criteria which had not been communicated to the laboratory. Few patients (7.8%) with rejected specimens were treated with acyclovir, which suggests a low clinical concern for HSV encephalitis. Acceptance criteria based on CSF parameters and host immune status saved time and cost and did not miss patients with HSV CNS infection. Communication between the clinician and the laboratory is imperative for a successful screening program.Early recognition of herpes simplex virus (HSV) encephalitis is crucial because prompt initiation of antiviral therapy improves clinical outcomes (17, 18). The detection of HSV DNA directly in cerebrospinal fluid (CSF) by PCR has been well validated for the diagnosis of herpes central nervous system (CNS) infections, and given its high sensitivity and specificity, HSV PCR is now recognized as the reference standard (1,4,9,12). HSV PCR has become one of the most commonly requested tests of CSF in our clinical microbiology laboratory, and there has been a costly trend toward overusing molecular diagnostics to evaluate patients with nonspecific complaints.Most patients with CNS infections have an elevated CSF leukocyte count and/or protein level (5,7,16). Screening the CSF cell count and protein values prior to performing HSV PCR has been suggested as a way to save healthcare costs without reducing sensitivity (13, 16). In addition, laboratory acceptance criteria for HSV testing of CSF have been shown to increase the proportion of positive results (from 1.9% to 4.0% at one institution) (13). Based on these findings, we implemented criteria for HSV PCR testing that are founded on CSF profiles in addition to host characteristics but had not previously been validated with our pro...

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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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The impact of an enteroviral RT-PCR assay on the diagnosis of aseptic meningitis and patient management

Cited by 80 publications

References 16 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

Validation of Laboratory Screening Criteria for Herpes Simplex Virus Testing of Cerebrospinal Fluid

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

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