Test Characteristics and Interpretation of Cerebrospinal Fluid Gram Stain in Children
Abstract
BACKGROUND: Few data exist regarding the test characteristics of cerebrospinal fluid (CSF) Gram stain among children at risk for bacterial meningitis, especially the rate of false positive Gram stain. METHODS: We conducted a retrospective cohort study of children seen in the emergency department of Children's Hospital Boston who had CSF obtained between December 1992 and September 2005. Patients who had ventricular shunts, as well as those who received antibiotics before CSF was obtained were excluded. Test characteristics of CSF Gram stain were assessed using CSF culture as the criterion standard. Patients were considered to have bacterial meningitis if there was either: (1) growth of a pathogen, or (2) growth of a possible pathogen noted on the final CSF culture report and the patient was treated with a course of parenteral antibiotics for 7 days or more without other indication. RESULTS: A total of 17,569 eligible CSF specimens were collected among 16,036 patients during the 13-year study period. The median age of study subjects was 74 days. Seventy CSF specimens (0.4%) had organisms detected on Gram stain. The overall sensitivity of Gram stain to detect bacterial meningitis was 67% [42 of 63; 95% confidence interval (CI): 54-78] with a positive predictive value of 60% (42 of 70; 95% CI: 48-71). Most patients without bacterial meningitis have negative Gram stain [specificity 99.9% (17,478 of 17,506; 95% CI: 99.8-99.9)] with a negative predictive value of 99.9 (17,478 of 17,499; 95% CI: 99.8-99.9). CONCLUSIONS: CSF Gram stain is appropriately used by physicians in risk stratification for the diagnosis and empiric treatment of bacterial meningitis in children. Although a positive Gram stain result greatly increases the likelihood of bacterial meningitis; the result may be because of contamination or misinterpretation in 40% of cases and should not, by itself, result in a full treatment course for bacterial meningitis.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Gram staining for bacteria in CSF has high specificity up to 100%, but sensitivity varies between 30% and 90% depending on the bacterial species.
“While specificity for the detection of bacteria is high—up to 100%— sensitivity varies between 30%–90% depending on the bacterial species (1–5).”
From Molecular diagnostics in cerebrospinal fluid for the diagnosis of central nervous system infections (2024) · cites this paper as [4]
Cites
Tunkel, A. R. (2001) · Cited by 308 · see citing works
Nigrovic, L. E. (2007) · JAMA · doi:10.1001/jama.297.1.52 · Cited by 306 · see citing works
Nigrovic, L. E., Kuppermann, N., & Malley, R. (2002) · PEDIATRICS · doi:10.1542/peds.110.4.712 · Cited by 172 · see citing works
Microscopic Examination and Broth Culture of Cerebrospinal Fluid in Diagnosis of Meningitis
Dunbar, S. A., Eason, R. A., Musher, D. M., & Clarridge, J. E. (1998) · Journal of Clinical Microbiology · doi:10.1128/jcm.36.6.1617-1620.1998 · Cited by 120 · see citing works
Bonsu, B. K., & Harper, M. B. (2004) · The Pediatric Infectious Disease Journal · doi:10.1097/01.inf.0000129689.58211.9e · Cited by 98 · see citing works
Self-citationSeverity of childhood bacterial meningitis and duration of illness before diagnosis
Kilpi, T. M., Anttila, M., Kallio, M., & Peltola, H. (1991) · The Lancet · doi:10.1016/0140-6736(91)91032-p · Cited by 88 · see citing works
Bacterial meningitis in infants: the epidemiology, clinical features, and prognostic factors
Chang, C.-J., Chang, W., Huang, L., Huang, S., Chang, Y., Hung, P., Lu, C., Chang, C.-S., Cheng, B., Lee, P.-Y., et al. (2003) · Brain and Development · doi:10.1016/s0387-7604(03)00122-0 · Cited by 76 · see citing works
Clinical decision rules to distinguish between bacterial and aseptic meningitis
Dubos, F. (2006) · Archives of Disease in Childhood · doi:10.1136/adc.2005.085704 · Cited by 76 · see citing works
Predictors of Bacterial Meningitis in the Era After Haemophilus influenzae
Freedman, S. B., Marrocco, A., Pirie, J., & Dick, P. T. (2001) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/archpedi.155.12.1301 · Cited by 70 · see citing works
Bacteral Meningitis in Childhood at the Children's Hospital of Pittsburgh: 1988-1998
Neuman, H. B., & Wald, E. R. (2001) · Clinical Pediatrics · doi:10.1177/000992280104001102 · Cited by 66 · see citing works
Meningococcal meningitis with ‘normal’ cerebrospinal fluid
Coll, M.-T., Uriz, M.-S., Pineda, V., Fontanals, D., Bella, F., Nava, J. M., Deulofeu, F., Morera, M.-A., Martí, C., Lite, J., et al. (1994) · Journal of Infection · doi:10.1016/s0163-4453(94)91197-5 · Cited by 65 · see citing works
Bacterial Meningitis Without Clinical Signs of Meningeal Irritation
Geiseler, P. J., & Nelson, K. E. (1982) · Southern Medical Journal · doi:10.1097/00007611-198204000-00018 · Cited by 37 · see citing works
Brief report. Neonatal meningitis: mortality, cerebrospinal fluid, and microbiological findings
Nel, E. (2000) · Journal of Tropical Pediatrics · doi:10.1093/tropej/46.4.237 · Cited by 33 · see citing works
Value of cerebrospinal fluid examination in the diagnosis of meningitis in the newborn.
Hristeva, L., Bowler, I. C. J. W., Booy, R., King, A., & Wilkinson, A. R. (1993) · Archives of Disease in Childhood · doi:10.1136/adc.69.5_spec_no.514 · Cited by 32 · see citing works
Wasier, A.-P., Chevret, L., Essouri, S., Durand, P., Chevret, S., & Devictor, D. J. (2005) · Pediatric Critical Care Medicine · doi:10.1097/01.pcc.0000170611.85012.01 · Cited by 31 · see citing works
Epidemiology and outcome of bacterial meningitis in Canadian children: 1998-1999.
Husain, E. H., Chawla, R., Dobson, S., & Davies, H. D. (2006) · PubMed · Cited by 27 · see citing works
Long-term Outcome for Children with Bacterial Meningitis in Rural Papua New Guinea
Wandi, F. (2004) · Journal of Tropical Pediatrics · doi:10.1093/tropej/fmh075 · Cited by 23 · see citing works
Williams, A. J., & Nadel, S. (2001) · CNS Drugs · doi:10.2165/00023210-200115120-00001 · Cited by 18 · see citing works
Evaluation of CSF Variables as a Diagnostic Test for Bacterial Meningitis
Deivanayagam, N., Ashok, T. P., Nedunchelian, K., Ahamed, S. S., & Mala, N. (1993) · Journal of Tropical Pediatrics · doi:10.1093/tropej/39.5.284 · Cited by 18 · see citing works
Bonsu, B. K., & Harper, M. B. (2005) · Academic Emergency Medicine · doi:10.1197/j.aem.2004.11.022 · Cited by 12 · see citing works
Self-citationHow rapidly is cerebrospinal fluid pleocytosis manifested with bacterial meningitis?
Leonardi, S., Leggio, T., Fischer, A., Sciacca, A., & Musumeci, S. (1989) · PubMed · Cited by 11 · see citing works
Coovadia, Y. M., & Solwa, Z. (1987) · PubMed · Cited by 11 · see citing works
Kanra, G., Akan, Ö., Ecevit, Z., Ceyhan, M., & Secmeer, G. (1996) · The Turkish Journal of Pediatrics · doi:10.24953/turkjpediatr.1996.3512 · Cited by 8 · see citing works
Sangalli, M., Palange, S., Fabrizi, E., Faustini, A., & Perucci, C. A. (2005) · PubMed · Cited by 4 · see citing works
[Absence of pleocytosis in bacterial meningitis].
Lt, J. (1987) · PubMed · Cited by 3 · see citing works
Flagged first, then by citations
2 of the 27 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
A Versatile PDMS/Paper Hybrid Microfluidic Platform for Sensitive Infectious Disease Diagnosis
Dou, M., Domínguez, D. C., Li, X., Sanchez, J., & Scott, G. (2014) · Analytical Chemistry · doi:10.1021/ac5021694 · Cited by 205 · see citing works
Arslan, F., Meynet, E., Sünbül, M., Sıpahı, O. R., Kurtaran, B., Kaya, S., İnkaya, A. Ç., Pagliano, P., Şengöz, G., Batırel, A. A., et al. (2015) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s10096-015-2346-5 · Cited by 93 · see citing works
Graf, E. H., Farquharson, M. V., & Cárdenas, A. M. (2017) · Diagnostic Microbiology and Infectious Disease · doi:10.1016/j.diagmicrobio.2016.09.022 · Cited by 71 · see citing works
Central Nervous System Infections
Archibald, L. K., & Quisling, R. G. (2013) · Springer eBooks · doi:10.1007/978-1-4471-5226-2_22 · Cited by 71 · see citing works
Srinivasan, L., Pisapia, J. M., Shah, S. S., Halpern, C. H., & Harris, M. C. (2012) · Annals of Emergency Medicine · doi:10.1016/j.annemergmed.2012.05.040 · Cited by 55 · see citing works
Improved Detection of Bacterial Central Nervous System Infections by Use of a Broad-Range PCR Assay
Meyer, T., Franke, G. C., Polywka, S., Lütgehetmann, M., Gbadamosi, J., Magnus, T. U., & Aepfelbacher, M. (2014) · Journal of Clinical Microbiology · doi:10.1128/jcm.00469-14 · Cited by 40 · see citing works
Molecular diagnostics in cerebrospinal fluid for the diagnosis of central nervous system infections
Olie, S. E., Andersen, C. Ø., van de Beek, D., & Brouwer, M. C. (2024) · Clinical Microbiology Reviews · doi:10.1128/cmr.00021-24 · Cited by 38 · see citing works
Bårnes, G. K., Gudina, E. K., Berhane, M., Abdissa, A., Tesfaw, G., Abebe, G., Feruglio, S. L., Caugant, D. A., & Jørgensen, H. J. (2018) · BMC Infectious Diseases · doi:10.1186/s12879-018-3589-4 · Cited by 37 · see citing works
Rothman, R. E., Ramachandran, P., Yang, S. S., Hardick, A., Won, H. H., Kecojević, A., Quianzon, C. C. L., Hsieh, Y., & Gaydos, C. A. (2010) · Academic Emergency Medicine · doi:10.1111/j.1553-2712.2010.00790.x · Cited by 37 · see citing works
Du, B., Hua, C., Xia, Y., Li, J., Xie, Y.-P., Tao, Y., Cao, Q., & Mo, X. (2019) · Annals of Translational Medicine · doi:10.21037/atm.2019.08.103 · Cited by 30 · see citing works
The clinical and laboratory diagnosis of acute meningitis and acute encephalitis
Cunha, B. A. (2013) · Expert Opinion on Medical Diagnostics · doi:10.1517/17530059.2013.804508 · Cited by 24 · see citing works
Indicators of external ventricular drainage-related infections—a retrospective observational study
Wiegand, J., Hickson, L., & Merz, T. M. (2016) · Acta Neurochirurgica · doi:10.1007/s00701-016-2709-4 · Cited by 21 · see citing works
Taniguchi, T., Tsuha, S., Shiiki, S., & Narita, M. (2020) · Annals of Clinical Microbiology and Antimicrobials · doi:10.1186/s12941-020-00404-9 · Cited by 18 · see citing works
Central Nervous System Infections
Zimmer, A. J., Burke, V. E., & Bloch, K. C. (2016) · Microbiology Spectrum · doi:10.1128/microbiolspec.dmih2-0012-2015 · Cited by 16 · see citing works
Berger‐Estilita, J., Passer, M., Giles, M., Wiegand, J., & Merz, T. M. (2018) · Acta Neurochirurgica · doi:10.1007/s00701-018-3643-4 · Cited by 15 · see citing works
Validation of Septic Knee Monoarthritis Prediction Rule in a Lyme Disease Endemic Area
Grant, D. S., Neville, D. N., Levas, M. N., Balamuth, F., Garro, A. C., Bennett, J. E., Thompson, A. D., Kharbanda, A. B., Lyons, T. W., Nigrovic, L. E., et al. (2021) · Pediatric Emergency Care · doi:10.1097/pec.0000000000002455 · Cited by 14 · see citing works
Cerebrospinal Fluid Pleocytosis in Children in the Era of Bacterial Conjugate Vaccines
Nigrovic, L. E., Malley, R., & Kuppermann, N. (2009) · Pediatric Emergency Care · doi:10.1097/pec.0b013e318196faeb · Cited by 13 · see citing works
Brizzi, K. T., Hines, E. M., McGowan, K. L., & Shah, S. S. (2011) · The Pediatric Infectious Disease Journal · doi:10.1097/inf.0b013e31823d7b6f · Cited by 12 · see citing works
Expanding Molecular Diagnostics for Central Nervous System Infections
Gutierrez, M., & Emmanuel, P. J. (2018) · Advances in Pediatrics · doi:10.1016/j.yapd.2018.04.005 · Cited by 11 · see citing works
Clinical utility of anaerobic culture of cerebrospinal fluid
Chatzopoulos, K., Shannon, S. K., & Schuetz, A. N. (2020) · Anaerobe · doi:10.1016/j.anaerobe.2020.102246 · Cited by 10 · see citing works
Molecular Approaches to the Diagnosis of Meningitis and Encephalitis
Bloch, K., & Tang, Y.-W. (2016) · Molecular Microbiology · doi:10.1128/9781555819071.ch24 · Cited by 10 · see citing works
External validation of the bacterial meningitis score in children hospitalized with meningitis.
Tuerlinckx, D., Hayeck, J. E., der Linden, D. V., Bodart, E., & Glupczynski, Y. (2012) · PubMed · doi:10.2143/acb.67.4.2062673 · Cited by 10 · see citing works
Ahmad, F., Brubaker, M. M., Rajendraprasad, S. S., Hoeynck, B., Clyde, B. L., & Velagapudi, M. (2021) · Cureus · doi:10.7759/cureus.17035 · Cited by 8 · see citing works
Filho, E. M., Horita, S. M., Gilio, A. E., Alves, A. C. D., & Nigrovic, L. E. (2013) · The Pediatric Infectious Disease Journal · doi:10.1097/inf.0b013e3182913e84 · Cited by 8 · see citing works
Isolation of bacterial cerebrospinal fluid culture contaminants at a major military medical center
Wong, P. H., Maranich, A. M., & Muench, D. F. (2013) · Diagnostic Microbiology and Infectious Disease · doi:10.1016/j.diagmicrobio.2013.08.019 · Cited by 8 · see citing works
TarvijEslami, S., Nassirian, H., Bayat-Mokhtari, M., Bahieh, Z. Z., Elham, H., Alimohamad, N., & Sobhani, E. (2011) · Pediatrics International · doi:10.1111/j.1442-200x.2011.03551.x · Cited by 7 · see citing works
Bacterial Meningitis Post–PCV7
Kowalsky, R. H., & Jaffe, D. M. (2013) · Pediatric Emergency Care · doi:10.1097/pec.0b013e318294f709 · Cited by 7 · see citing works
Ghoweba, Y., Shabestari, S. A. S., & Malik, Z. A. (2024) · Cureus · doi:10.7759/cureus.51906 · Cited by 6 · see citing works
Khanam, R., Hanif, M., Hoque, M. M., Tawfique, M., & Ahmed, A. N. U. (2013) · Bangladesh Journal of Child Health · doi:10.3329/bjch.v36i3.14275 · Cited by 6 · see citing works
Enrichment culture of CSF is of limited value in the diagnosis of neonatal meningitis
Chaudhry, S. H., Wagstaff, D., Gupta, A., Bowler, I. C. J. W., & Webster, D. P. (2011) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s10096-011-1163-8 · Cited by 5 · see citing works
Keskin, E., Öz, M., Çakır, Y., Çubuk, F., Hasbek, M., & Büyüktuna, S. A. (2024) · Türk Mikrobiyoloji Cemiyeti Dergisi · doi:10.54453/tmcd.2024.49091 · Cited by 4 · see citing works
Winzor, G., & Atabani, S. F. (2021) · Archives of Disease in Childhood Education & Practice · doi:10.1136/archdischild-2020-321242 · Cited by 3 · see citing works
Balamuth, F., Cruz, A. T., Freedman, S. B., Ishimine, P. T., Garro, A. C., Curtis, S. J., Grether-Jones, K. L., Miller, A. S., Uspal, N. G., Schmidt, S. M., et al. (2018) · Pediatric Emergency Care · doi:10.1097/pec.0000000000001639 · Cited by 3 · see citing works
Haas, H. (2009) · Médecine et Maladies Infectieuses · doi:10.1016/j.medmal.2009.02.025 · Cited by 2 · see citing works
“Study of Estimation of Cerebrospinal Fluid C-Reactive Protein in Diagnosis of Acute Meningitis.”
Bansal, D. K., Bhatt, D. D., Dadhich, D. S. K., & Kariya, D. (2021) · Pediatric Review International Journal of Pediatric Research · doi:10.17511/ijpr.2021.i04.02 · Cited by 2 · see citing works
Molecular Approaches to the Diagnosis of Meningitis and Encephalitis
Bloch, K. C., & Tang, Y. (2011) · Molecular Microbiology · doi:10.1128/9781555816834.ch50 · Cited by 2 · see citing works
Ba-Abbad, S., Dahbour, A., Akileh, M., Ghaith, B., & Dahbour, S. S. (2022) · Jordan Medical Journal · doi:10.35516/jmj.v56i3.354 · Cited by 1 · see citing works
Heideman, L. C., & Nigrovic, L. E. (2024) · The Pediatric Infectious Disease Journal · doi:10.1097/inf.0000000000004304 · Cited by 1 · see citing works
Chahid, N., Lazraq, S., Souhli, R. A., Elhassouni, M., Harrak, K. E., Tazi, E. G., Bousgheïri, F., Najdi, A., & Rissoul, K. (2026) · Cureus · doi:10.7759/cureus.110050 · Cited by 1 · see citing works
Is the diagnosis and treatment of childhood acute bacterial meningitis in Turkey evidence-based?
TÜREL, Ö., & Bakır, M. (2014) · TURKISH JOURNAL OF MEDICAL SCIENCES · doi:10.3906/sag-1304-19 · Cited by 1 · see citing works
Central Nervous System Infections
Zimmer, A. J., Burke, V. E., & Bloch, K. C. (2016) · ASM Press eBooks · doi:10.1128/9781555819040.ch24 · Cited by 1 · see citing works
Central Nervous System Infections
Archibald, L. K., Ritter, A. S., & Kalyatanda, G. (2024) · Springer eBooks · doi:10.1007/978-3-031-62220-5_31 · Cited by 1 · see citing works
Sulik, A., & Ołdak, E. (2009) · Pediatria Polska · doi:10.1016/s0031-3939(09)70160-x · Cited by 1 · see citing works
Rojas-Rosas, L. F., Flórez, I. D., Sierra, J. M., & Ochoa, W. C. (2013) · DOAJ (DOAJ: Directory of Open Access Journals)
Álvarez, M. D. (n.d.) · DOAJ (DOAJ: Directory of Open Access Journals)
Incidence of meningitis in infants with simple febrile seizures. Experience in a 3th level hospital
Rojas-Rosas, L. F., Flórez, I. D., Sierra, J. M., & Ochoa, W. C. (2013) · Institutional Repository University of Antioquia (University of Antioquia)
Álvarez, M. D., Arias, M. I. A., Alés, L. R., Isás, D. C., García, M. I. M., & Vázquez, O. M. (2011) · DOAJ (DOAJ: Directory of Open Access Journals)
Test Characteristics and Interpretation of Cerebrospinal Fluid Gram Stain in Children
Bissell, M. G. (2009) · Yearbook of Pathology and Laboratory Medicine · doi:10.1016/s1077-9108(08)79112-6
Test Characteristics and Interpretation of Cerebrospinal Fluid Gram Stain in Children
Stockman, J. A. (2010) · Yearbook of Pediatrics · doi:10.1016/s0084-3954(09)79282-6
Rahajamanana, V. L., Andriatahiana, D. S., Andrianjakasolo, P., Raboba, J. L., Ratovohery, A., & Rasamindrakotroka, A. (2022) · International Journal of Research in Medical Sciences · doi:10.18203/2320-6012.ijrms20221328
Rahman, S. N., Hossain, S. M. M., & Ashraf, R. (2022) · Scholars Academic Journal of Biosciences · doi:10.36347/sajb.2022.v10i11.008
Mugheri, D., Qazi, M. A., & Abbasi, K. A. (2022) · doi:10.53555/jptcp.v30i19.3806
Humphries, R. M., Faron, M. L., Dekker, J. P., Ledeboer, N. A., & Buchan, B. W. (2023) · ClinMicroNow · doi:10.1002/9781683674849.mcm0039
Humphries, R. M., Faron, M. L., Dekker, J. P., Ledeboer, N. A., & Buchan, B. W. (2023) · ClinMicroNow · doi:10.1002/9781683670438.mcm0039 · Cited by 1 · see citing works
Ventriculoperitoneal Shunts: What General Pediatricians Should Know
Hauptman, J. S., & Jackson, E. M. (2025) · Pediatrics in Review · doi:10.1542/pir.2023-005969
Ayele, L., & Balcha, F. (2026) · Canadian Journal of Infectious Diseases and Medical Microbiology · doi:10.1155/cjid/4447180
Ayele, L., Asrat, D., Seman, A., Aman, J., Tefera, M., Mesele, D. W., Alemu, A., Mulu, A., Alemayehu, D. H., Mihret, A., et al. (2026) · Diagnostics · doi:10.3390/diagnostics16172800
- Authors
- Neuman, M. I., Tolford, S., & Harper, M. B.
- Affiliations
- Boston Children's Hospital (US)
- Corresponding author
- Neuman, Mark I.
- Venue
- Pediatric Infectious Disease Journal
- Published
- 2008-04
- Volume
- 27
- Issue
- 4
- Pages
- 309-313
- ISSN
- 0891-3668 (ISSN-L)
- OpenAlex
- W1987584916
- Cited by
- 57
- References
- 27
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 5 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 2 · 2019: 1 · 2018: 4 · 2016: 5 · 2015: 1 · 2014: 3 · 2013: 9 · 2012: 2
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Pediatric Infectious Disease Journal (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Bacterial Identification and Susceptibility Testing
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Neonatal and Maternal Infections
- Keywords
- bacterial meningitis, children, diagnostic accuracy, false positives, cerebrospinal fluid culture, sensitivity and specificity, empirical antibiotic therapy, risk stratification
- MeSH terms
- Bacteria, Boston, Cerebrospinal Fluid, Child, Preschool, False Positive Reactions, Gentian Violet, Humans, Infant, Phenazines, Predictive Value of Tests, Retrospective Studies, Sensitivity and Specificity, Cohort Studies, Meningitis, Bacterial
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
