Skip to main content
PMC home page
Journal of Clinical Microbiology logoLink to Journal of Clinical Microbiology
. 1994 Sep;32(9):2120–2127. doi: 10.1128/jcm.32.9.2120-2127.1994

Concordance of endotoxemia with gram-negative bacteremia in patients with gram-negative sepsis: a meta-analysis.

J C Hurley 1
PMCID: PMC263953  PMID: 7814535

Abstract

The Limulus amebocyte lysate (LAL) assay is a sensitive method for detecting endotoxin. Using gram-negative (GN) bacteremia as the basis for comparison, concordance with endotoxemia in 45 studies could be expressed as an odds ratio. Calculation of summary odds ratios by the Mantel-Haenszel-Peto method indicated that the concordance of the results was no higher by the chromogenic LAL assay than by the gelation version, and the sensitivity was improved by only 11% (62 versus 51%). Endotoxemia was detected in 77 (68%) of 114 patients with bacteremia caused by an organism that was not a member of the family Enterobacteriaceae, whereas endotoxemia was detected in only 120 (45%) of 269 patients with bacteremia caused by a member of the family Enterobacteriaceae or an anaerobe (P < 0.001). This difference was also apparent for patients with GN bacteremia for whom a fatal outcome had been recorded. The prevalence of GN bacteremia in the tested population and the type of etiological agent are critical and previously unrecognized variables which affect the interpretation of the LAL test in patients with suspected sepsis.

Full text

PDF
2120

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adinolfi L. E., Utili R., Gaeta G. B., Perna P., Ruggiero G. Presence of endotoxemia and its relationship to liver dysfunction in patients with typhoid fever. Infection. 1987;15(5):359–362. doi: 10.1007/BF01647740. [DOI] [PubMed] [Google Scholar]
  2. Andersen B. M., Solberg O. Endotoxin liberation and invasivity of Neisseria meningitidis. Scand J Infect Dis. 1984;16(3):247–254. doi: 10.3109/00365548409070397. [DOI] [PubMed] [Google Scholar]
  3. Andersen L. W., Baek L., Degn H., Lehd J., Krasnik M., Rasmussen J. P. Presence of circulating endotoxins during cardiac operations. J Thorac Cardiovasc Surg. 1987 Jan;93(1):115–119. [PubMed] [Google Scholar]
  4. Bailey M. E. Endotoxin, bile salts and renal function in obstructive jaundice. Br J Surg. 1976 Oct;63(10):774–778. doi: 10.1002/bjs.1800631011. [DOI] [PubMed] [Google Scholar]
  5. Bion J. F., Badger I., Crosby H. A., Hutchings P., Kong K. L., Baker J., Hutton P., McMaster P., Buckels J. A., Elliott T. S. Selective decontamination of the digestive tract reduces gram-negative pulmonary colonization but not systemic endotoxemia in patients undergoing elective liver transplantation. Crit Care Med. 1994 Jan;22(1):40–49. doi: 10.1097/00003246-199401000-00011. [DOI] [PubMed] [Google Scholar]
  6. Bone R. C., Fisher C. J., Jr, Clemmer T. P., Slotman G. J., Metz C. A., Balk R. A. A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med. 1987 Sep 10;317(11):653–658. doi: 10.1056/NEJM198709103171101. [DOI] [PubMed] [Google Scholar]
  7. Brandtzaeg P., Bryn K., Kierulf P., Ovstebø R., Namork E., Aase B., Jantzen E. Meningococcal endotoxin in lethal septic shock plasma studied by gas chromatography, mass-spectrometry, ultracentrifugation, and electron microscopy. J Clin Invest. 1992 Mar;89(3):816–823. doi: 10.1172/JCI115660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Brandtzaeg P., Kierulf P., Gaustad P., Skulberg A., Bruun J. N., Halvorsen S., Sørensen E. Plasma endotoxin as a predictor of multiple organ failure and death in systemic meningococcal disease. J Infect Dis. 1989 Feb;159(2):195–204. doi: 10.1093/infdis/159.2.195. [DOI] [PubMed] [Google Scholar]
  9. Butler T., Bell W. R., Levin J., Linh N. N., Arnold K. Typhoid fever. Studies of blood coagulation, bacteremia, and endotoxemia. Arch Intern Med. 1978 Mar;138(3):407–410. doi: 10.1001/archinte.138.3.407. [DOI] [PubMed] [Google Scholar]
  10. Butler T., Levin J., Do Quang C. u., Walker R. I. Bubonic plague: detection of endotoxemia with the limulus test. Ann Intern Med. 1973 Nov;79(5):642–646. doi: 10.7326/0003-4819-79-5-642. [DOI] [PubMed] [Google Scholar]
  11. Butler T., Levin J., Linh N. N., Chau D. M., Adickman M., Arnold K. Yersinia pestis infection in Vietnam. II. Quantiative blood cultures and detection of endotoxin in the cerebrospinal fluid of patients with meningitis. J Infect Dis. 1976 May;133(5):493–499. doi: 10.1093/infdis/133.5.493. [DOI] [PubMed] [Google Scholar]
  12. Casey W. F., Hauser G. J., Hannallah R. S., Midgley F. M., Khan W. N. Circulating endotoxin and tumor necrosis factor during pediatric cardiac surgery. Crit Care Med. 1992 Aug;20(8):1090–1096. doi: 10.1097/00003246-199208000-00004. [DOI] [PubMed] [Google Scholar]
  13. Clumeck N., Lauwers S., Kahn A., Mommens M., Butzler J. P. Apport du "test limule" au diagnostic des endotoxinémies et des méningites à germes Gram-négatif. Nouv Presse Med. 1976 Apr 23;6(17):1451–1454. [PubMed] [Google Scholar]
  14. Cooperstock M., Riegle L. Plasma Limulus gelation assay in infants and children: correlation with gram negative bacterial infection and evidence for "intestinal endotoxemia". Prog Clin Biol Res. 1985;189:329–345. [PubMed] [Google Scholar]
  15. Danner R. L., Elin R. J., Hosseini J. M., Wesley R. A., Reilly J. M., Parillo J. E. Endotoxemia in human septic shock. Chest. 1991 Jan;99(1):169–175. doi: 10.1378/chest.99.1.169. [DOI] [PubMed] [Google Scholar]
  16. Danner R. L., Natanson C., Elin R. J., Hosseini J. M., Banks S., MacVittie T. J., Parrillo J. E. Pseudomonas aeruginosa compared with Escherichia coli produces less endotoxemia but more cardiovascular dysfunction and mortality in a canine model of septic shock. Chest. 1990 Dec;98(6):1480–1487. doi: 10.1378/chest.98.6.1480. [DOI] [PubMed] [Google Scholar]
  17. Das J., Schwartz A. A., Folkman J. Clearance of endotoxin by platelets: role in increasing the accuracy of the Limulus gelation test and in combating experimental endotoxemia. Surgery. 1973 Aug;74(2):235–240. [PubMed] [Google Scholar]
  18. Dofferhoff A. S., Bom V. J., de Vries-Hospers H. G., van Ingen J., vd Meer J., Hazenberg B. P., Mulder P. O., Weits J. Patterns of cytokines, plasma endotoxin, plasminogen activator inhibitor, and acute-phase proteins during the treatment of severe sepsis in humans. Crit Care Med. 1992 Feb;20(2):185–192. doi: 10.1097/00003246-199202000-00007. [DOI] [PubMed] [Google Scholar]
  19. Dolan S. A., Riegle L., Berzofsky R., Cooperstock M. Clinical evaluation of the plasma chromogenic Limulus assay. Prog Clin Biol Res. 1987;231:405–416. [PubMed] [Google Scholar]
  20. Elin R. J., Hosseini J. Clinical utility of the Limulus amebocyte lysate (LAL) test. Prog Clin Biol Res. 1985;189:307–327. [PubMed] [Google Scholar]
  21. Elin R. J., Robinson R. A., Levine A. S., Wolff S. M. Lack of clinical usefulness of the limulus test in the diagnosis of endotoxemia. N Engl J Med. 1975 Sep 11;293(11):521–524. doi: 10.1056/NEJM197509112931102. [DOI] [PubMed] [Google Scholar]
  22. Exley A. R., Leese T., Holliday M. P., Swann R. A., Cohen J. Endotoxaemia and serum tumour necrosis factor as prognostic markers in severe acute pancreatitis. Gut. 1992 Aug;33(8):1126–1128. doi: 10.1136/gut.33.8.1126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Feldman S., Pearson T. A. The Limulus test and gram-negative bacillary sepsis. Am J Dis Child. 1974 Aug;128(2):172–174. doi: 10.1001/archpedi.1974.02110270046009. [DOI] [PubMed] [Google Scholar]
  24. Fossard D. P., Kakkar V. V. The Limulus test in experimental and clinical endotoxaemia. Br J Surg. 1974 Oct;61(10):798–804. doi: 10.1002/bjs.1800611013. [DOI] [PubMed] [Google Scholar]
  25. Függer R., Hamilton G., Rogy M., Herbst F., Kwasny W., Schemper M., Schultz F. Prognostic significance of endotoxin determination in patients with severe intraabdominal infection. J Infect Dis. 1990 Jun;161(6):1314–1315. doi: 10.1093/infdis/161.6.1314. [DOI] [PubMed] [Google Scholar]
  26. Goodman S. N. Have you ever meta-analysis you didn't like? Ann Intern Med. 1991 Feb 1;114(3):244–246. doi: 10.7326/0003-4819-114-3-244. [DOI] [PubMed] [Google Scholar]
  27. Harris R. I., Stone P. C., Stuart J. An improved chromogenic substrate endotoxin assay for clinical use. J Clin Pathol. 1983 Oct;36(10):1145–1149. doi: 10.1136/jcp.36.10.1145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Harthug S., Bjorvatn B., Osterud B. Quantitation of endotoxin in blood from patients with meningococcal disease using a limulus lysate test in combination with chromogenic substrate. Infection. 1983 Jul-Aug;11(4):192–195. doi: 10.1007/BF01641194. [DOI] [PubMed] [Google Scholar]
  29. Hass A., Rossberg M. I., Hodes H. L., Hyatt A. C., Hodes D. S. Endotoxin levels in immunocompromised children with fever. J Pediatr. 1986 Aug;109(2):265–269. doi: 10.1016/s0022-3476(86)80383-3. [DOI] [PubMed] [Google Scholar]
  30. Hurley J. C. Sepsis management and antiendotoxin therapy after nebacumab. A reappraisal. Drugs. 1994 Jun;47(6):855–861. doi: 10.2165/00003495-199447060-00001. [DOI] [PubMed] [Google Scholar]
  31. Hurley J. C., Tosolini F. A., Louis W. J. Quantitative Limulus lysate assay for endotoxin and the effect of plasma. J Clin Pathol. 1991 Oct;44(10):849–854. doi: 10.1136/jcp.44.10.849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Ingoldby C. J., Skinner C., Giles G. R. A comparison of methods of removing inhibitors to the chromogenic Limulus assay in normal and jaundiced blood. Thromb Res. 1986 Oct 1;44(1):95–100. doi: 10.1016/0049-3848(86)90184-2. [DOI] [PubMed] [Google Scholar]
  33. Jacob A. I., Goldberg P. K., Bloom N., Degenshein G. A., Kozinn P. J. Endotoxin and bacteria in portal blood. Gastroenterology. 1977 Jun;72(6):1268–1270. [PubMed] [Google Scholar]
  34. Jirillo E., Fumarola D., Marcuccio L., Papadia L. L., Pasquetto N., Monno R., De Rinaldis P. Endotossemia e malnutrizione. Minerva Pediatr. 1977 Feb 28;29(2):139–142. [PubMed] [Google Scholar]
  35. Joiner K. A., Hammer C. H., Brown E. J., Cole R. J., Frank M. M. Studies on the mechanism of bacterial resistance to complement-mediated killing. I. Terminal complement components are deposited and released from Salmonella minnesota S218 without causing bacterial death. J Exp Med. 1982 Mar 1;155(3):797–808. doi: 10.1084/jem.155.3.797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Kelsey M. C., Lipscomb A. P., Mowles J. M. Limulus amoebocyte lysate endotoxin test: an aid to the diagnosis in the septic neonate? J Infect. 1982 Jan;4(1):69–72. doi: 10.1016/s0163-4453(82)91104-5. [DOI] [PubMed] [Google Scholar]
  37. Klein K., Fuchs G. J., Kulapongs P., Mertz G., Suskind R. M., Olson R. E. Endotoxemia in protein-energy malnutrition. J Pediatr Gastroenterol Nutr. 1988 Mar-Apr;7(2):225–228. doi: 10.1097/00005176-198803000-00012. [DOI] [PubMed] [Google Scholar]
  38. Kuratana M., Anderson P. Host metabolites that phenotypically increase the resistance of Haemophilus influenzae type b to clearance mechanisms. J Infect Dis. 1991 May;163(5):1073–1079. doi: 10.1093/infdis/163.5.1073. [DOI] [PubMed] [Google Scholar]
  39. Levin J., Poore T. E., Young N. S., Margolis S., Zauber N. P., Townes A. S., Bell W. R. Gram-negative sepsis: detection of endotoxemia with the limulus test. With studies of associated changes in blood coagulation, serum lipids, and complement. Ann Intern Med. 1972 Jan;76(1):1–7. doi: 10.7326/0003-4819-76-1-1. [DOI] [PubMed] [Google Scholar]
  40. Levin J., Poore T. E., Zauber N. P., Oser R. S. Detection of endotoxin in the blood of patients with sepsis due to gran-negative bacteria. N Engl J Med. 1970 Dec 10;283(24):1313–1316. doi: 10.1056/NEJM197012102832404. [DOI] [PubMed] [Google Scholar]
  41. Levin J., Tomasulo P. A., Oser R. S. Detection of endotoxin in human blood and demonstration of an inhibitor. J Lab Clin Med. 1970 Jun;75(6):903–911. [PubMed] [Google Scholar]
  42. Leying H., Suerbaum S., Kroll H. P., Stahl D., Opferkuch W. The capsular polysaccharide is a major determinant of serum resistance in K-1-positive blood culture isolates of Escherichia coli. Infect Immun. 1990 Jan;58(1):222–227. doi: 10.1128/iai.58.1.222-227.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Liao W., Florén C. H. Hyperlipidemic response to endotoxin--a part of the host-defence mechanism. Scand J Infect Dis. 1993;25(6):675–682. doi: 10.3109/00365549309008562. [DOI] [PubMed] [Google Scholar]
  44. Lumsden A. B., Henderson J. M., Alspaugh J. Endotoxemia during percutaneous manipulation of the obstructed biliary tree. Am J Surg. 1989 Jul;158(1):21–24. doi: 10.1016/0002-9610(89)90308-5. [DOI] [PubMed] [Google Scholar]
  45. MANTEL N., HAENSZEL W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959 Apr;22(4):719–748. [PubMed] [Google Scholar]
  46. Magliulo E., Scevola D., Fumarola D., Vaccaro R., Bertotto A., Burberi S. Clinical experience in detecting endotoxemia with the limulus test in typhoid fever and other Salmonella infections. Infection. 1976;4(2):21–24. doi: 10.1007/BF01638343. [DOI] [PubMed] [Google Scholar]
  47. Martinez L. A., Quintiliani R., Tilton R. C. Clinical experience on the detection of endotoxemia with the limulus test. J Infect Dis. 1973 Jan;127(1):102–105. doi: 10.1093/infdis/127.1.102. [DOI] [PubMed] [Google Scholar]
  48. McCartney A. C., Banks J. G., Clements G. B., Sleigh J. D., Tehrani M., Ledingham I. M. Endotoxaemia in septic shock: clinical and post mortem correlations. Intensive Care Med. 1983;9(3):117–122. doi: 10.1007/BF01772577. [DOI] [PubMed] [Google Scholar]
  49. Mellado M. C., Rodríguez-Contreras R., Fernandez-Crehuet M., Lopez-Gigosos R., Delgado Rodriguez M., Galvez-Vargas R. Endotoxin liberation by strains of N. meningitidis isolated from patients and healthy carriers. Epidemiol Infect. 1991 Apr;106(2):289–295. doi: 10.1017/s0950268800048433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Oberle M. W., Graham G. G., Levin J. Detection of endotoxemia with the Limulus test: preliminary studies in severely malnourished children. J Pediatr. 1974 Oct;85(4):570–573. doi: 10.1016/s0022-3476(74)80473-7. [DOI] [PubMed] [Google Scholar]
  51. PORTER P. J., SPIEVACK A. R., KASS E. H. ENDOTOXIN-LIKE ACTIVITY OF SERUM FROM PATIENTS WITH SEVERE LOCALIZED INFECTIONS. N Engl J Med. 1964 Aug 27;271:445–447. doi: 10.1056/NEJM196408272710905. [DOI] [PubMed] [Google Scholar]
  52. Pearson F. C., Dubczak J., Weary M., Bruszer G., Donohue G. Detection of endotoxin in the plasma of patients with gram-negative bacterial sepsis by the Limulus amoebocyte lysate assay. J Clin Microbiol. 1985 Jun;21(6):865–868. doi: 10.1128/jcm.21.6.865-868.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Peduzzi P., Shatney C., Sheagren J., Sprung C. Predictors of bacteremia and gram-negative bacteremia in patients with sepsis. The Veterans Affairs Systemic Sepsis Cooperative Study Group. Arch Intern Med. 1992 Mar;152(3):529–535. [PubMed] [Google Scholar]
  54. Roantree R. J., Rantz L. A. A STUDY OF THE RELATIONSHIP OF THE NORMAL BACTERICIDAL ACTIVITY OF HUMAN SERUM TO BACTERIAL INFECTION. J Clin Invest. 1960 Jan;39(1):72–81. doi: 10.1172/JCI104029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Rocke D. A., Gaffin S. L., Wells M. T., Koen Y., Brock-Utine J. G. Endotoxemia associated with cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1987 Jun;93(6):832–837. [PubMed] [Google Scholar]
  56. Roth R. I., Levin F. C., Levin J. Optimization of detection of bacterial endotoxin in plasma with the Limulus test. J Lab Clin Med. 1990 Aug;116(2):153–161. [PubMed] [Google Scholar]
  57. Saubolle M. A., Jorgensen J. H. Use of the Limulus amebocyte lysate test as a cost-effective screen for gram-negative agents of meningitis. Diagn Microbiol Infect Dis. 1987 Jul;7(3):177–183. doi: 10.1016/0732-8893(87)90002-2. [DOI] [PubMed] [Google Scholar]
  58. Scheifele D. W., Melton P., Whitchelo V. Evaluation of the Limulus test for endotoxemia in neonates with suspected sepsis. J Pediatr. 1981 Jun;98(6):899–903. doi: 10.1016/s0022-3476(81)80582-3. [DOI] [PubMed] [Google Scholar]
  59. Scheifele D. W., Olsen E. M., Pendray M. R. Endotoxinemia and thrombocytopenia during neonatal necrotizing enterocolitis. Am J Clin Pathol. 1985 Feb;83(2):227–229. doi: 10.1093/ajcp/83.2.227. [DOI] [PubMed] [Google Scholar]
  60. Schiller N. L., Joiner K. A. Interaction of complement with serum-sensitive and serum-resistant strains of Pseudomonas aeruginosa. Infect Immun. 1986 Dec;54(3):689–694. doi: 10.1128/iai.54.3.689-694.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Schlichting E., Lyberg T., Solberg O., Andersen B. M. Endotoxin liberation from Neisseria meningitidis correlates to their ability to induce procoagulant and fibrinolytic factors in human monocytes. Scand J Infect Dis. 1993;25(5):585–594. doi: 10.3109/00365549309008547. [DOI] [PubMed] [Google Scholar]
  62. Schulman K. A., Glick H. A., Rubin H., Eisenberg J. M. Cost-effectiveness of HA-1A monoclonal antibody for gram-negative sepsis. Economic assessment of a new therapeutic agent. JAMA. 1991 Dec 25;266(24):3466–3471. [PubMed] [Google Scholar]
  63. Shenep J. L., Flynn P. M., Barrett F. F., Stidham G. L., Westenkirchner D. F. Serial quantitation of endotoxemia and bacteremia during therapy for gram-negative bacterial sepsis. J Infect Dis. 1988 Mar;157(3):565–568. doi: 10.1093/infdis/157.3.565. [DOI] [PubMed] [Google Scholar]
  64. Stumacher R. J., Kovnat M. J., McCabe W. R. Limitations of the usefulness of the Limulus assay for endotoxin. N Engl J Med. 1973 Jun 14;288(24):1261–1264. doi: 10.1056/NEJM197306142882402. [DOI] [PubMed] [Google Scholar]
  65. Togari H., Mikawa M., Iwanaga T., Matsumoto N., Kawase A., Hagisawa M., Ogino T., Goto R., Watanabe I., Kito H. Endotoxin clearance by exchange blood transfusion in septic shock neonates. Acta Paediatr Scand. 1983 Jan;72(1):87–91. doi: 10.1111/j.1651-2227.1983.tb09669.x. [DOI] [PubMed] [Google Scholar]
  66. Usawattanakul W., Tharavanij S., Limsuwan A. Tachypleus lysate test for endotoxin in patients with Gram negative bacterial infections. Southeast Asian J Trop Med Public Health. 1979 Mar;10(1):13–17. [PubMed] [Google Scholar]
  67. Wortel C. H., von der Möhlen M. A., van Deventer S. J., Sprung C. L., Jastremski M., Lubbers M. J., Smith C. R., Allen I. E., ten Cate J. W. Effectiveness of a human monoclonal anti-endotoxin antibody (HA-1A) in gram-negative sepsis: relationship to endotoxin and cytokine levels. J Infect Dis. 1992 Dec;166(6):1367–1374. doi: 10.1093/infdis/166.6.1367. [DOI] [PubMed] [Google Scholar]
  68. Yoshida M., Obayashi T., Tamura H., Tanaka S., Kawai T., Sakamoto S., Miura Y. Diagnostic and prognostic significance of plasma endotoxin determination in febrile patients with haematological malignancies. Eur J Cancer. 1994;30A(2):145–147. doi: 10.1016/0959-8049(94)90074-4. [DOI] [PubMed] [Google Scholar]
  69. Yusuf S., Peto R., Lewis J., Collins R., Sleight P. Beta blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis. 1985 Mar-Apr;27(5):335–371. doi: 10.1016/s0033-0620(85)80003-7. [DOI] [PubMed] [Google Scholar]
  70. Ziegler E. J., Fisher C. J., Jr, Sprung C. L., Straube R. C., Sadoff J. C., Foulke G. E., Wortel C. H., Fink M. P., Dellinger R. P., Teng N. N. Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. A randomized, double-blind, placebo-controlled trial. The HA-1A Sepsis Study Group. N Engl J Med. 1991 Feb 14;324(7):429–436. doi: 10.1056/NEJM199102143240701. [DOI] [PubMed] [Google Scholar]
  71. van Deventer S. J., Buller H. R., ten Cate J. W., Sturk A., Pauw W. Endotoxaemia: an early predictor of septicaemia in febrile patients. Lancet. 1988 Mar 19;1(8586):605–609. doi: 10.1016/s0140-6736(88)91412-2. [DOI] [PubMed] [Google Scholar]
  72. van Deventer S. J., de Vries I., Statius van Eps L. W., Pauw W., Büller H. R., Sturk A., ten Cate J. W. Endotoxemia, bacteremia and urosepsis. Prog Clin Biol Res. 1988;272:213–224. [PubMed] [Google Scholar]
  73. van Dissel J. T., van Furth R., Compier B. A., Feuth H. D., Frolich M. Survival in selected patients with gram-negative sepsis after adjunctive therapy with HA-1A. Lancet. 1993 Apr 10;341(8850):959–960. doi: 10.1016/0140-6736(93)91250-p. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Microbiology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES