CLINICAL MICROBIOLOGY REVIEWS, Oct. 1989, p. 329-353 Vol. 2, No. 4 0893-8512/89/040329-25$02.00/0 Copyright © 1989, American Society for Microbiology Clinical Implications of Positive Blood Cultures CHARLES S. BRYAN Department of Medicine, University of South Carolina School of Medicine and Richland Memorial Hospital, Columbia, South Carolina 29203 INTRODUCTION ........................................ 330 A HISTORICAL PERSPECTIVE........................................ 330 INTERPRETATION OF BLOOD CULTURES ........................................ 331 False-Positive Versus True-Positive Blood Cultures........................................ 331 Duration ........................................ 331 Clinical Severity and Intensity ........................................ 332 Downloaded from EPIDEMIOLOGY ........................................ 332 Frequency ........................................ 332 Lethality ........................................ 333 Host Factors ........................................ 333 THE CLINICAL SETTING ........................................ 334 Nosocomial Versus Community Acquired ........................................ 334 Primary Versus Secondary ........................................ 334 Unimicrobial Versus Polymicrobial ........................................ 335 SPECIFIC MICROORGANISMS ........................................ 335 http://cmr.asm.org/ Aerobic Gram-Positive Bacteria ........................................ 335 Staphylococcus aureus ........................................ 335 Coagulase-negative staphylococci ........................................ 336 Streptococcus pneumoniae........................................ 336 The viridans streptococci ........................................ 337 Group A streptococci (S. pyogenes) ........................................ 337 Group B streptococci (S. agalactiae) ........................................ 337 Enterococci ........................................ 337 Streptococcus bovis........................................ 338 Non-group A, B, or D streptococci........................................ 338 on March 13, 2015 by guest Corynebacterium species........................................ 338 Listeria monocytogenes........................................ 338 Bacillus species infections ......................................... 338 Erysipelothrix rhusiopathiae ........................................ 338 Aerobic Gram-Negative Bacteria ........................................ 339 Neisseria species........................................ 339 Haemophilus influenzae........................................ 339 Other Haemophilus species ........................................ 339 The family Enterobacteriaceae ........................................ 339 Salmonella and Shigella species ........................................ 340 The family Pseudomonadaceae ........................................ 340 Acinetobacter calcoaceticus ........................................ 340 Aeromonas hydrophila ........................................ 340 Pasteurella multocida........................................................................................................340 Yersinia species ........................................ 340 Vibrio species ........................................ 341 Campylobacter species........................................................... 341 Dysgonic fermenters ......................................... 341 Other gram-negative bacteria ......................................... 341 Anaerobic Bacteria ........................................ 341 Fungi......................................... 342 Mycobacteria ......................................... 343 CURRENT PERSPECTIVES......................................... 343 Blood Cultures ......................................... 343 Presumptive and Precise Antimicrobial Therapy ......................................... 343 Future Directions ......................................... 344 ACKNOWLEDGMENTS ......................................... 345 LITERATURE CITED ......................................... 345 329 330 BRYAN CLIN. MICROBIOL. REV. INTRODUCTION The goals of medicine are accurate diagnosis, useful prognosis, and effective therapy. Toward each of these BLOOD CULTURES goals, clinicians find positive blood cultures to be invaluable. However, interpretation of blood cultures is fraught with subtleties and potential pitfalls. This review will focus pri- 100 marily on the significance of positive blood cultures from a z GRAM-POSITIVE BACTEREMIAS clinical perspective. w A HISTORICAL PERSPECTIVE 0- 0o 10 By 1940, the practice of obtaining blood for cultures from 0 febrile patients had become well established (114). In early \GRAM-NEGATIVE 1941, Chester S. Keefer of Boston summarized his extensive BACTEREMIAS personal experience in a review entitled "The Clinical Downloaded from Significance of Bacteremia" (176). Later the same year, penicillin G was introduced into clinical practice. A perspec- FLINGEMIAS tive on changes brought about by antibiotics and other advances can be gained by comparing Keefer's data with those from any large present-day hospital. Of Keefer's 479 cases of bacteremia, 250 were due to hemolytic streptococci, most of which were presumably group A streptococci (Streptococcus pyogenes). These bac- 0.1 http://cmr.asm.org/ teremias were associated with a 70% mortality rate. Keefer 1977 1980 1984 1988 reported 122 cases of Staphylococcus aureus bacteremia and YEAR 54 cases of pneumococcal both of which were bacteremia, FIG. 1. Relationship between number of blood cultures proc- associated with 80% mortality rates. Gram-negative bacter- essed and documentation of bacteremia and fungemia at a municipal emias accounted for only 11% of Keefer's cases. Most of teaching hospital, 1977-1988 (semilogarithmic scale). these (40 of 53 bacteremias) were due to Escherichia coli, which was associated with a 35% mortality rate. Today, group A streptococci account for fewer than 2% of positive blood cultures at most hospitals (48, 346). The death tures, especially in patients without a clinically obvious rates associated with gram-positive bacteremias have been localized infection. For instance, unexplained hemolytic on March 13, 2015 by guest reduced to about one-third their former levels. Although the streptococcal bacteremia raised the possibility of throm- impact of antibiotic therapy on gram-positive bacteremias bophlebitis of the veins of the pelvis or the neck. Unex- was dramatic, an increased frequency and importance of plained S. aureus bacteremia suggested either endocarditis gram-negative bacteremias soon became evident (111). At or osteomyelitis "that has failed to produce localizing symp- Boston City Hospital, for example, the number of bactere- toms" (176). Pneumococcal bacteremia without pneumonia mias per 1,000 patient admissions nearly quadrupled (from might arise from osteomyelitis, sinusitis, peritonitis, or en- 7.4 to 28.0) between 1935 and 1972, due in large measure to docarditis. E. coli bacteremia without an obvious source hospital-acquired gram-negative rod infections (222). The raised the possibility of biliary tract obstruction, multiple overall mortality rate among patients with gram-negative rod liver abscesses, or cirrhosis. In the latter respect, Keefer bacteremia was 39% in studies published between 1950 and anticipated the diverse syndromes of spontaneous bacterial 1970 (309). In a more recent series, 40% of all bacteremias peritonitis (77). Today, an enormous body of literature were due to members of either the family Enterobac- attests to the relevance of such correlations. teriaceae or the family Pseudomonadaceae, and these bac- Because microorganisms other than bacteria were seldom teremias were associated with a 36% mortality rate (48, 55). isolated from blood cultures in the pre-antibiotic era, it was To some extent, the rising incidence of positive blood appropriate for Keefer to equate "positive blood culture" cultures may reflect the more frequent use of blood cultures with "bacteremia." The rising frequency of fungal blood by clinicians. Shown in Fig. 1 are data from Richland isolates explains a recent trend to speak of "bacteremia and Memorial Hospital, Columbia, S.C., a 600-bed municipal fungemia" (353). However, "bacteremia and fungemia" teaching facility. Between 1977 and 1988, the number of does not entirely suffice, since other kinds of microorgan- patients admitted to this hospital each year remained rela- isms are being identified in blood cultures, especially as a tively constant (23,106 in 1977; 22,847 in 1988). However, result of the acquired immunodeficiency syndrome (AIDS). the number of blood cultures processed by the laboratory It is significant that, while a 1973 monograph was entitled each year nearly tripled (from 5,692 to 14,384). The number Bacteremia (303), a 1988 monograph is entitled Bloodstream of gram-negative bacteremias encountered each year rose Infections (314). modestly (from 170 to 242), but the number of gram-positive The term bloodstream infections also has a limitation: the bacteremias rose markedly (from 412 to 934) and the number mere presence of microorganisms in blood denotes neither of fungemias rose dramatically (from 3 to 65). The resur- active multiplication nor harmful consequences. In other gence of gram-positive bacteremias and the new importance words, the presence of microorganisms in blood can be of fungemias (149) are now widely appreciated. "incidental" (123). "Sepsis"