Scandinavian Journal of Infectious Diseases
ISSN: 0036-5548 (Print) 1651-1980 (Online) Journal homepage: http://www.tandfonline.com/loi/infd19
Bacteremia in a General Hospital: A Prospective Study of 102 Consecutive Cases Ole B. Jepsen & Bent Korner To cite this article: Ole B. Jepsen & Bent Korner (1975) Bacteremia in a General Hospital: A Prospective Study of 102 Consecutive Cases, Scandinavian Journal of Infectious Diseases, 7:3, 179-184, DOI: 10.3109/inf.1975.7.issue-3.05 To link to this article: http://dx.doi.org/10.3109/inf.1975.7.issue-3.05
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Date: 20 April 2016, At: 09:32
Scand J Infect Dis 7; 179-184, 1975
Bacteremia in a General Hospital A Prospective Study of 102 Consecutive Cases
OLE B. JEPSEN and BENT KORNER
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From the Department of Clinical Microbiology, Bispebjerg Hospital, Cooenhagen, Denmark
ABSTRACT. A prospective clinical-bacteriological study of 102 consecutive cases of confirmed bacteremia at a Copenhagen City general hospital was carried out during 5 months of 1973 with special concern given to focus of infection and acquisition of microorganisms. Valid positive cultures were obtained from 7.2 patients per 1000 admissions. 50 of the 102 bacteremias were by aUprobability acquired in the hospital, mainly due to transurethral manipulations or intravenous lines. Pneumonia and hepatobiliary infections accounted for most of the non-hospital acquired bacteremias. 26/102 patients died in relation to the bacteremia. Escherichia coli and Staphylococcus aureus caused more than half of the infections. Bacteremia caused by proteus, klebsiella, enterobacter species or staphylococci was in most cases nosocomial and carried the highest mortality, i.e, 40 %, versus 15 % when other organisms were responsible. It is concluded that nosocomial bacteremia is a frequent and life-endangering complication which is often preceded by certain diagnostic or therapeutic procedures, not invariably linked to severe underlyIng diseases. Consequently, attempts to reduce bacteremic episodes should include surveiUance of ecological factors and certain hospital procedures.
INTRODUCTION Recent papers have dealt with the mortality rate of bacteremia and the treatment of this condition with various antibiotics (l, 9). The incidence and fatality rates of bacteremia, underlying diseases and other host-related factors have been discussed in other papers (7, 10,14). Today hospital beds are to a large extent occupied by infection-prone elderly patients and in these patients antibiotics have apparently failed to reduce the overall mortality of bacteremia. The present paper concerns a prospective clinical and bacteriological study of 102 consecutive cases of bacteremia in a general hospital with particular attention given to the focus of infection. MATERIAL AND METHODS The investigation was earned out from January through May 1973 at Bispebjerg Hospital, a general hospital of 1200 beds in Copenhagen. From patients with clinical signs of bacteremia a maximum of 16 ml blood was sampled under aseptic conditions, usually and preferably by 2 separate venipunctures. As a rule pre-evacuated tubes mounted with a cannula (Venulev) containing 1 ml sodium polyanetholesulfonate solution were used, but in urgent cases at times of the day when the bacteriological laboratory was closed, 5 ml of blood was drawn in an ordinary disposable syringe and
distributed into 2 screw-capped bottles each containing 50 ml of Truches medium (0.9% saline with4% peptones and 0.2 % glucose). The bottles were immediately incubated at 37°C and regularly inspected for signs of growth, in which case microscopy was carried out and subcultures were made. Blood taken in the Venule was inoculated into 12 tubes, of which 4 contained nutrient broth (filtered ox broth with .5% ox serum), 4 contained semisolid nutrient agar (filtered ox broth with 0.2% Bacto-agar (Difco), and 4 were tubes of semisolid thioglycollate agar (filtered ox broth with 0.3 % thioglycollate, 5% pepsin-digested horse blood and 0.2 % Bacto-agar (Difco The tubes were incubated at 37°C for 18-24 hours before microscopy and subcultures were earned out from tubes with growth. Subcultures were made on relevant plate media, and the isolated strains were identified in the laboratory. All negative tubes were incubated under regular observation for 6 days. The technique used allowed for detection of anaerobic bacteria. During the period of investigation. 1700 samples from approximately 1000 patients were received in the laboratory. Growth occurred in 23.7% of the samples. In the laboratory a presumptive distinction was attempted between growth representing true bacteremia and exogenous contamination of the blood. 14.4% of the total number of blood samples was considered to represent bacteremia in 102patients. The diagnosis was verified at bedside by one of us and agreed upon by the clinicians in charge of the patient. Procuring of cultures from other sites prior to antimicrobial therapy was urged. At the same time essential clinical data were recorded on computer coded cards and a distinction between com-
».
Scand J Infect Dis 7
180 O. B. Jepsen and B. Komer
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Table I. 102 patients with bacteremia. grouped according to disease leading to hospitalization Diseased organ or tissue
N
Kidney and urinary tract, acute disease Kidney and urinary tract, chronic disease Heart and peripheral circulatory system Lungs and respiratory tract Pancreas, liver and biliary tract Gastrointestinal tract Bones and joints Haematopoietic organs Central nervous system Metabolic, endocrine Others Total
16 16 19 15 II
5 4 4 3 3 6 102
14 patients had malignant neoplasm. II patients had diabetes mellitus.
munity acquired and nosocomial bacteremia was made using criteria given by the U.S. Department of Health (16). When the patients were discharged the prospectively collected information was supplemented by a review of their charts.
RESULTS During the 5 months of investigation 13929 patients were admitted to the hospital. Blood cultures were made in 7.1 % of the patients. The diagnosis of bacteremia was clinically established and bacteriologically confirmed in 102 patients. Thus, the incidence of bacteremia was 7.2 per 1000 admissions. Among the 102 patients with confirmed bacteremia 56 were women. 15 patients were over 80 years, 68 patients 60-79, 16 patients 50-59, and only 3 below 50 years of age. The groups of diseases that led to admission are summarized in Table I. 29 patients had an indwelling catheter or had undergone instrumentation through the urethra just prior to the bacteremia, 17 patients had an intravenous line at the time of bacteremia, and 16 were subject to both procedures. In 14 patients a malignant cancer was found and 4 of these died with bacteremia. One third of the total cases were surgical. The bacteria isolated from the bacteremic patients are presented in Table II in comparison with corresponding figures from a recent survey covering several Danish hospitals (4). In 10 patients multiple isolates were found either in the same sample or in successive specimens, bringing the Scand J Infect Dis 7
number of strains to a total of 114. The following tables, however, refer to the first or dominating isolate only, and thus are concerned with 102 patients and 102 strains. Table III presents the distribution of cases according to possible focus of infection for 4 groups of bacteria, covering 97 of the 102 patients, including all deaths. In 10 patients the focus of underlying infection remained obscure, and in another II patients there were either several possibilities or the focus could not be diagnosed with sufficient certainty. Staphylococcal pneumonia and suppurative phlebitis associated with intravenous lines accounted for 10 of 25 staphylococcal bacteremias, while infections in wounds and in the urinary tract were responsible for another 6 cases. Four cases of bacteremia, in which the nature of the primary infection could not be properly defined, were most likely due to infected wounds in 2 patients, intravenous line phlebitis in I and urinary tract infection in the other. 30 out of 52 cases of gram-negative bacteremia by enteric bacteria (E. coli, proteus, klebsiella or enterobacter) were secondary to infections in the urinary tract and 10 were secondary to diseases in the biliary tract. In 6 patients the focus was not demonstrated with sufficient certainty, but could have been urinary tract infection in 3, enteritis in 2 and wound infection in I. Table II. Percentage distribution of 114 bacterial strains isolated from 102 cases of bacteremia at Bispebjerg Hospital compared with a Danish materialfrom several hospitals (Henrichsen, 1974)
Organism Escherichia coli Staphylococcus aureus Klebsiella spp., Enterobacter spp. Streptococcus faecalis Streptococcus pneumoniae Proteus spp. Haemolytic streptococci" Non-haemolytic streptococci Pseudomonas aeruginosa Staphylococcus albus Neisseria meningitidis Total a
Bispebjerg Henrichsen (ref. 4) Hospital (N=114) (N=161O) % % 31.6 24.6
30.6 17.1
11.4 7.9 6.1 5.3 3.5 2.6 1.7 0.9
8.1 3.8 2.1 8.3 1.7 4.5 3.9 10.9 0.9
100.0
91.9
4.4
Soluble haemolysin demonstrated.
Bacteremia in a general hospital
181
Table III. Distribution of cases ofbacteremia according to possible focus ofinfection , groups ofpathogens and deaths
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Group of pathogens Staph. aureus Deaths E. coli Deaths Other enterobacteria Deaths Streptococci Deaths Total Deaths a
Urinary Unknown Uncertain tract
Biliary tract
Respiratory Bones and Lv. line tract Wounds joints
3 3 3 0
4 0 4 1
3 1 21 2
0 0 7 2
5
1 0 3 0 10 3
2 2
9 3 3 0 36 6
3
0 0 7
I
0 11
3
I
0 0 10 3
I
0 0
I
12 2
3 2 0 0
2 2 0 0
5 1 0 0
1 0 1 0 5 2
0 0 0 0 2 2
0 0 1 I
6 2
Others Total 0 0 0 0
25 10 35 5
4" 2 5 3
17 7 20 4 97 26
Including 3 cases of endocarditis.
Streptococcal (including pneumococcal) infections were in most cases pneumonia or endocarditis. The one uncertain case in this group was probably a mute endocarditis. It appeared that though bacteremia with a focus in the urinary tract caused more than one third of the total number of bacteremia cases, less than one fourth of the fatalities were due to this type of infection. It should be noted that in 25 of the 36 cases of urogenic bacteremia a urethral catheter had been passed prior to the bacteremia, and many of the patients had a typical history of chills and rapidly rising temperature in close relation to the instrumentation. 26 patients died in conjunction with the bacteremia (Table IV), and in these the bacterial invasion of the blood stream was considered to represent a major contribution to the fatal outcome. Bacteremia due to staphylococci, proteus,
klebsiella or enterobacter species had a lethality of
40% (17/42) as opposed to 15% (9/60) when other bacteria were responsible. Hospital and community acquired bacteremias each constituted one half of the material (Table V). Two thirds of the nosocomial bacteremia cases were caused by staphylococci, proteus, klebsiella or enterobacter strains, thus indicating a somewhat higher lethality for the nosocomial group than for the group representing community acquired infection. In Tables VI and VII, the infection and/or underlying diseases are listed for 17 patients that died with bacteremia due to one of those apparently virulent bacteria. Only 3 of the patients had a
Table V. Comparison between community acquired bacteremia and hospital acquired bacteremia with regard to pathogens and fatalities No. of patients with
Table IV. Distribution of fatalities according to pathogens Organism
No. of patients Total Dead
Staphylococcus aureus Proteus, Klebsiella, Enterobacter spp. Escherichia coli Streptococci Others Total
Community acquired bacteremia
Hospital acquired bacteremia
Total Dead
Total Dead
% dead
Organism
10
40
17
7
35 20 5 102
5 4 0 26
40 15 20
Staphylococcus aureus 5 Proteus, Klebsiella, Enterobacter spp. 5 Escherichia coli 20 Streptococci 15 Others 5 Total 50
25
25
2 3 3 0 9(18%)
20
9
12 15 5 0
5
52
2 I
0 17(33%)
Scand J Infect Dis 7
182 O. B. Jepsen and B. Korner
Table VI. /0 fatal cases of bacteremia due to Staphylococcus aureus Pat. no.
(y.)
Sex
Infection and/or associated disease
23 35 37 40 62 68
76 69 73 79 72 67 70 55 76
F M F F F M F F M
Pyelonephritis ac., nephropathia Pneumonia Fractura colli femoris Pyarthrosis humeri Hypernephroma Diabetes, osteitis metatarsale Nephropathia acuta; anuria Strictura oesophagi, benign Ca. prostatae, urethritis suppurativa
89
69
M
Alcoholismus chronica, pneumonia
I
15 17
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Age
malignant cancer, and though many suffered from severe diseases-some being desperately ill-a substantial fraction had trivial benign diseases. DISCUSSION A positive blood culture may represent bacteremia, contamination of the sample, or both. The number of positive samples, the type of microorganism present and the growth rate and density are helpful factors in deciding which is the case (8, 13). In this study we were additionally aided by simultaneous cultures from other sites and information about antibiotic treatment at the time of blood sampling. The clinical examination of the patients revealed that the diagnosis could be made in the laboratory with fair precision provided the above-mentioned data were available. The bacteria isolated from bacteremic patients were the same as those found by Henrichsen (4) and
Procedure probably related Focus of to bacteremia infection
Acquisition of bacteremia
Nephrectomy None Osteosynthesis None None None None I.v, line Indwelling catheter None
In community
Operation wound In hospital Lungs In hospital Operation wound In hospital Joint In hospital In hospital ? In hospital Bone In hospital ? I.v. line In hospital Urethra In hospital ?
they appeared with a similar frequency. In both study groups gram-negative enteric bacteria accounted for about one half of the isolates. Coagulase-positive staphylococci were more frequent in our series, probably owing to local endemic factors. Our isolation rate of pneumococci and other streptococci was also higher than that found by Henrichsen. This may reflect a better survival of these bacteria in the samples due to our shorter line of transportation within the hospital. In Henrichsen's much larger series from 1965 and 1971 anaerobic bacteria were found in 4-5 % of the cases. No anaerobic infections occurred in our patients, but considering the size of our study group, the absence of such cases is only weakly significant. The incidence of polymicrobial growth was comparable to findings from the Mayo Clinic (17). Staphylococcal bacteremia originating from the site of intravenous infusion was found in 5 or proba-
Table VII. Seven fatal cases of bacteremia due to Proteus, Klebsiella or Enterobacter spp. UTI=urinary tract infection Pat. no.
Age (y.)
Sex
Infection and/or associated disease
2
73
M
Diabetes, UTI
5 20
69 80
F F
Pyelonephritis chronica Pyelonephritis chronica
38
79
M
Fractura colli femoris, UTI
63
62
F
67 97
66 78
F F
Choledocholithiasis, abscessus pancreatis Ca. pancreatis, peritonitis purulenta Diabetes, UTI
Scand J Infect Dis 7
Procedure probably related Focus of to bacteremia infection Indwelling catheter None Indwelling catheter Indwelling catheter None None None
Acquisition of bacteremia
Urinary tract
In hospital
? ?
In hospital In hospital
Urinary tract
In hospital
Biliary tract
In hospital
Peritoneal cavity In community Renal abscess In community
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Bacteremia in a general hospital bly 6 patients. One infection was fatal, stressing the need for revision and surveillance of this procedure (2,3,5). Gram-negative bacteremia due to enteric bacteria was almost exclusively found in patients with primary disease in the urinary or biliary tract. Infection in the urinary tract was by far the most frequent focus of bacteremia, and in two thirds of these cases the bacteremia was secondary to instrumentation of the urethra. It has long been known that manipulations within the urinary tract are associated with a high frequency of bacteremia (6, 12). Recently, this was confirmed by Sullivan et al. (15) who found a prevalence ranging from 31 % to 8 % according to the type of instrumentation. Like Watt and Okubadejo (18) we think that a disproportionate representation within the present hospital population of patients in whom such procedures are performed may account for the dominance of gram-negative bacteremia. In this context it is of interest that in 1973 a total of 28445 urethral catheters of all sorts were delivered from the central supply service in this hospital for use among approximately 30000 patients. In 1966 the corresponding figures were 16231 catheters and about 26000 patients. Owing to the obvious difficulties in comparing different groups of patients, the overall mortality of 25 % found in this material is a figure of little significance. However, staphylococcal bacteremia had a lethality of 40 %, which is the same as stated in a Danish survey of 462 cases from 1957-1960 (11). Thus, it appears that staphylococcal bacteremia, though less frequent and caused by other phage types than 15 years ago, still carries the same lethality. In the present investigation gram-negative bacteremia caused by enteric bacteria other than E. coli was fatal in 40% of cases. Bacteremia with these bacteria (proteus, klebsiella, enterobacter species) and with staphylococci was in most cases nosocomial, explaining the higher lethality in hospital-acquired bacteremia. It might be postulated that the high morbidity and lethality of nosocomial infection with these bacteria were due to serious underlying diseases in these patients. This was true in some cases, but in others the onset of bacteremia was unexpected and the fatal outcome unpredictable. The term nosocomial infection as used in this study, i.e. infection neither present nor incubating 24 hours after admission (16), does not indicate any
183
information about whether the infection was preventable. In this study one patient per 1000 admissions died with hospital-acquired bacteremia. Assuming that re-inforced prophylactic measures could reduce the lethality of nosocomial bacteremia by one tenth, 1 or 2 patients might be saved each year in this hospital alone. This study has shown that bacteria probably often resident in the hospital caused two thirds of bacteremias acquired in the hospital. This group of bacteria carried the highest lethality and was the cause of infection not only in patients suffering from severe underlying diseases, but also in patients with trivial illnesses. Attempts to reduce the frequency and mortality of bacteremia should therefore include considerations of ecological factors as well as hospital procedures likely to be followed by infections with virulent bacteria.
REFERENCES 1. Chalmers, J. P. & Tiller, D. 1.: Effect of treatment on
2. 3. 4. 5. 6. 7. 8.
9. 10. II.
12.
the mortality rate in septicaemia. Br Med J 2: 338, 1969. Darrell, J. H. & Garrod, L. P.: Secondary septicaemia from intravenous cannulae. Br MedJ 2:481, 1969. Freeman, J. B., Lemire, A. & MacLean, L. D.: Intravenous alimentation and septicemia. Surg Gynecol Obstet 135: 708, 1972. Henrichsen, J.: Recent trends of isolates from cases of bacteremia in Denmark. Scand J Infect Dis 6: 145, 1974. Hjorth, A. & Siboni, K.: Infusioner og septisk phlebitis. Nord Med 82:845, 1969. Hodgin, U. G. & Sanford, J. P.: Gram-negative rod bacteremia. An analysis of 100 patients. Am J Med 39:952, 1965. Kluge, R. M. & DuPont, H. L.: Factors affecting mortality of patients with bacteremia. Surg Gynecol Obstet 137: 267, 1973. MacGregor, R. R. & Beaty, H. N.: Evaluation of positive blood cultures. Guidelines for early differentiation of contaminated from valid positive cultures. Arch Intern Med 130: 84, 1972. McGowan, J. E., Barnes, M. W. & Finland, M.: Host-pathogen-drug interactions in surgical patients with bacteremia. Surg GynecolObstet 138: 50, 1974. Rogers, D. E., Koenig, M. G. & Holmes, K. K.: The problem of gram-negative bacteremia and its management. South MedJ 58: 1391, 1965. Rosendal, K., Faber, V., Hove, K., Jessen, O. & Eriksen, K. R.: Stafylokok-bakteriremi. IV. Bakteriologiske, epidemiologiske og kliniske iagttagelser i 462 tilftelde fra arene 1957-1960. Ugeskr Laeger 124: 459, 1962. Scott, W. W.: Bloodstream infections in urology. J Uro121: 527, 1929. Scand J Infect Dis 7
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184 O. B. Jepsen and B. Korner 13. Siboni, K.: Klinisk-bakteriologisk vurdering af bloddyrkninger med veekst. Ugeskr Laeger 124:464, 1962. 14. Siegenthaler, W., Vetter, H., Luthy. R. & Siegenthaler, G.: Klinik und antibiotische Therapie der bakteriellen septischen Erkrankungen in der inneren Medizin. Verhandlungen der Deutschen Gesellschaft fur innere Medizin, p. 805. 1. F. Bergmann, Munchen 1971. 15. Sullivan, M. M., Sutter, V. L., Mirns, M. M., Marsh, V. H. & Finegold, S. M.: Clinical aspects of bacteremia after manipulation of the genito-urinary tract. J Infect Dis 127:49,1973. 16. U.S. Department of Health, Education, and Welfare: Outline for surveillance and control of nosocomial infections. Center for Disease Control, Atlanta 1972. 17. Washington, J. A.: Comparison of two commercially available media for detection of bacteremia. Appl Microbiol22: 604, 1971. 18. Watt, P. 1. & Okubadejo, O. A.: Changes in incidence and aetiology of bacteremia arising in hospital practice. Br Med J I: 210, 1967.
Addressfor reprints: O. B. Jepsen, M.D., Department ofAntibiotics, Statens Seruminstitut, Amager Boulevard 80, DK-2300 Copenhagen S, Denmark
Scand J Infect Dis 7
ISSN: 0036-5548 (Print) 1651-1980 (Online) Journal homepage: http://www.tandfonline.com/loi/infd19
Bacteremia in a General Hospital: A Prospective Study of 102 Consecutive Cases Ole B. Jepsen & Bent Korner To cite this article: Ole B. Jepsen & Bent Korner (1975) Bacteremia in a General Hospital: A Prospective Study of 102 Consecutive Cases, Scandinavian Journal of Infectious Diseases, 7:3, 179-184, DOI: 10.3109/inf.1975.7.issue-3.05 To link to this article: http://dx.doi.org/10.3109/inf.1975.7.issue-3.05
Published online: 02 Jan 2015.
Submit your article to this journal
Article views: 1
View related articles
Citing articles: 4 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=infd19 Download by: [McMaster University]
Date: 20 April 2016, At: 09:32
Scand J Infect Dis 7; 179-184, 1975
Bacteremia in a General Hospital A Prospective Study of 102 Consecutive Cases
OLE B. JEPSEN and BENT KORNER
Downloaded by [McMaster University] at 09:32 20 April 2016
From the Department of Clinical Microbiology, Bispebjerg Hospital, Cooenhagen, Denmark
ABSTRACT. A prospective clinical-bacteriological study of 102 consecutive cases of confirmed bacteremia at a Copenhagen City general hospital was carried out during 5 months of 1973 with special concern given to focus of infection and acquisition of microorganisms. Valid positive cultures were obtained from 7.2 patients per 1000 admissions. 50 of the 102 bacteremias were by aUprobability acquired in the hospital, mainly due to transurethral manipulations or intravenous lines. Pneumonia and hepatobiliary infections accounted for most of the non-hospital acquired bacteremias. 26/102 patients died in relation to the bacteremia. Escherichia coli and Staphylococcus aureus caused more than half of the infections. Bacteremia caused by proteus, klebsiella, enterobacter species or staphylococci was in most cases nosocomial and carried the highest mortality, i.e, 40 %, versus 15 % when other organisms were responsible. It is concluded that nosocomial bacteremia is a frequent and life-endangering complication which is often preceded by certain diagnostic or therapeutic procedures, not invariably linked to severe underlyIng diseases. Consequently, attempts to reduce bacteremic episodes should include surveiUance of ecological factors and certain hospital procedures.
INTRODUCTION Recent papers have dealt with the mortality rate of bacteremia and the treatment of this condition with various antibiotics (l, 9). The incidence and fatality rates of bacteremia, underlying diseases and other host-related factors have been discussed in other papers (7, 10,14). Today hospital beds are to a large extent occupied by infection-prone elderly patients and in these patients antibiotics have apparently failed to reduce the overall mortality of bacteremia. The present paper concerns a prospective clinical and bacteriological study of 102 consecutive cases of bacteremia in a general hospital with particular attention given to the focus of infection. MATERIAL AND METHODS The investigation was earned out from January through May 1973 at Bispebjerg Hospital, a general hospital of 1200 beds in Copenhagen. From patients with clinical signs of bacteremia a maximum of 16 ml blood was sampled under aseptic conditions, usually and preferably by 2 separate venipunctures. As a rule pre-evacuated tubes mounted with a cannula (Venulev) containing 1 ml sodium polyanetholesulfonate solution were used, but in urgent cases at times of the day when the bacteriological laboratory was closed, 5 ml of blood was drawn in an ordinary disposable syringe and
distributed into 2 screw-capped bottles each containing 50 ml of Truches medium (0.9% saline with4% peptones and 0.2 % glucose). The bottles were immediately incubated at 37°C and regularly inspected for signs of growth, in which case microscopy was carried out and subcultures were made. Blood taken in the Venule was inoculated into 12 tubes, of which 4 contained nutrient broth (filtered ox broth with .5% ox serum), 4 contained semisolid nutrient agar (filtered ox broth with 0.2% Bacto-agar (Difco), and 4 were tubes of semisolid thioglycollate agar (filtered ox broth with 0.3 % thioglycollate, 5% pepsin-digested horse blood and 0.2 % Bacto-agar (Difco The tubes were incubated at 37°C for 18-24 hours before microscopy and subcultures were earned out from tubes with growth. Subcultures were made on relevant plate media, and the isolated strains were identified in the laboratory. All negative tubes were incubated under regular observation for 6 days. The technique used allowed for detection of anaerobic bacteria. During the period of investigation. 1700 samples from approximately 1000 patients were received in the laboratory. Growth occurred in 23.7% of the samples. In the laboratory a presumptive distinction was attempted between growth representing true bacteremia and exogenous contamination of the blood. 14.4% of the total number of blood samples was considered to represent bacteremia in 102patients. The diagnosis was verified at bedside by one of us and agreed upon by the clinicians in charge of the patient. Procuring of cultures from other sites prior to antimicrobial therapy was urged. At the same time essential clinical data were recorded on computer coded cards and a distinction between com-
».
Scand J Infect Dis 7
180 O. B. Jepsen and B. Komer
Downloaded by [McMaster University] at 09:32 20 April 2016
Table I. 102 patients with bacteremia. grouped according to disease leading to hospitalization Diseased organ or tissue
N
Kidney and urinary tract, acute disease Kidney and urinary tract, chronic disease Heart and peripheral circulatory system Lungs and respiratory tract Pancreas, liver and biliary tract Gastrointestinal tract Bones and joints Haematopoietic organs Central nervous system Metabolic, endocrine Others Total
16 16 19 15 II
5 4 4 3 3 6 102
14 patients had malignant neoplasm. II patients had diabetes mellitus.
munity acquired and nosocomial bacteremia was made using criteria given by the U.S. Department of Health (16). When the patients were discharged the prospectively collected information was supplemented by a review of their charts.
RESULTS During the 5 months of investigation 13929 patients were admitted to the hospital. Blood cultures were made in 7.1 % of the patients. The diagnosis of bacteremia was clinically established and bacteriologically confirmed in 102 patients. Thus, the incidence of bacteremia was 7.2 per 1000 admissions. Among the 102 patients with confirmed bacteremia 56 were women. 15 patients were over 80 years, 68 patients 60-79, 16 patients 50-59, and only 3 below 50 years of age. The groups of diseases that led to admission are summarized in Table I. 29 patients had an indwelling catheter or had undergone instrumentation through the urethra just prior to the bacteremia, 17 patients had an intravenous line at the time of bacteremia, and 16 were subject to both procedures. In 14 patients a malignant cancer was found and 4 of these died with bacteremia. One third of the total cases were surgical. The bacteria isolated from the bacteremic patients are presented in Table II in comparison with corresponding figures from a recent survey covering several Danish hospitals (4). In 10 patients multiple isolates were found either in the same sample or in successive specimens, bringing the Scand J Infect Dis 7
number of strains to a total of 114. The following tables, however, refer to the first or dominating isolate only, and thus are concerned with 102 patients and 102 strains. Table III presents the distribution of cases according to possible focus of infection for 4 groups of bacteria, covering 97 of the 102 patients, including all deaths. In 10 patients the focus of underlying infection remained obscure, and in another II patients there were either several possibilities or the focus could not be diagnosed with sufficient certainty. Staphylococcal pneumonia and suppurative phlebitis associated with intravenous lines accounted for 10 of 25 staphylococcal bacteremias, while infections in wounds and in the urinary tract were responsible for another 6 cases. Four cases of bacteremia, in which the nature of the primary infection could not be properly defined, were most likely due to infected wounds in 2 patients, intravenous line phlebitis in I and urinary tract infection in the other. 30 out of 52 cases of gram-negative bacteremia by enteric bacteria (E. coli, proteus, klebsiella or enterobacter) were secondary to infections in the urinary tract and 10 were secondary to diseases in the biliary tract. In 6 patients the focus was not demonstrated with sufficient certainty, but could have been urinary tract infection in 3, enteritis in 2 and wound infection in I. Table II. Percentage distribution of 114 bacterial strains isolated from 102 cases of bacteremia at Bispebjerg Hospital compared with a Danish materialfrom several hospitals (Henrichsen, 1974)
Organism Escherichia coli Staphylococcus aureus Klebsiella spp., Enterobacter spp. Streptococcus faecalis Streptococcus pneumoniae Proteus spp. Haemolytic streptococci" Non-haemolytic streptococci Pseudomonas aeruginosa Staphylococcus albus Neisseria meningitidis Total a
Bispebjerg Henrichsen (ref. 4) Hospital (N=114) (N=161O) % % 31.6 24.6
30.6 17.1
11.4 7.9 6.1 5.3 3.5 2.6 1.7 0.9
8.1 3.8 2.1 8.3 1.7 4.5 3.9 10.9 0.9
100.0
91.9
4.4
Soluble haemolysin demonstrated.
Bacteremia in a general hospital
181
Table III. Distribution of cases ofbacteremia according to possible focus ofinfection , groups ofpathogens and deaths
Downloaded by [McMaster University] at 09:32 20 April 2016
Group of pathogens Staph. aureus Deaths E. coli Deaths Other enterobacteria Deaths Streptococci Deaths Total Deaths a
Urinary Unknown Uncertain tract
Biliary tract
Respiratory Bones and Lv. line tract Wounds joints
3 3 3 0
4 0 4 1
3 1 21 2
0 0 7 2
5
1 0 3 0 10 3
2 2
9 3 3 0 36 6
3
0 0 7
I
0 11
3
I
0 0 10 3
I
0 0
I
12 2
3 2 0 0
2 2 0 0
5 1 0 0
1 0 1 0 5 2
0 0 0 0 2 2
0 0 1 I
6 2
Others Total 0 0 0 0
25 10 35 5
4" 2 5 3
17 7 20 4 97 26
Including 3 cases of endocarditis.
Streptococcal (including pneumococcal) infections were in most cases pneumonia or endocarditis. The one uncertain case in this group was probably a mute endocarditis. It appeared that though bacteremia with a focus in the urinary tract caused more than one third of the total number of bacteremia cases, less than one fourth of the fatalities were due to this type of infection. It should be noted that in 25 of the 36 cases of urogenic bacteremia a urethral catheter had been passed prior to the bacteremia, and many of the patients had a typical history of chills and rapidly rising temperature in close relation to the instrumentation. 26 patients died in conjunction with the bacteremia (Table IV), and in these the bacterial invasion of the blood stream was considered to represent a major contribution to the fatal outcome. Bacteremia due to staphylococci, proteus,
klebsiella or enterobacter species had a lethality of
40% (17/42) as opposed to 15% (9/60) when other bacteria were responsible. Hospital and community acquired bacteremias each constituted one half of the material (Table V). Two thirds of the nosocomial bacteremia cases were caused by staphylococci, proteus, klebsiella or enterobacter strains, thus indicating a somewhat higher lethality for the nosocomial group than for the group representing community acquired infection. In Tables VI and VII, the infection and/or underlying diseases are listed for 17 patients that died with bacteremia due to one of those apparently virulent bacteria. Only 3 of the patients had a
Table V. Comparison between community acquired bacteremia and hospital acquired bacteremia with regard to pathogens and fatalities No. of patients with
Table IV. Distribution of fatalities according to pathogens Organism
No. of patients Total Dead
Staphylococcus aureus Proteus, Klebsiella, Enterobacter spp. Escherichia coli Streptococci Others Total
Community acquired bacteremia
Hospital acquired bacteremia
Total Dead
Total Dead
% dead
Organism
10
40
17
7
35 20 5 102
5 4 0 26
40 15 20
Staphylococcus aureus 5 Proteus, Klebsiella, Enterobacter spp. 5 Escherichia coli 20 Streptococci 15 Others 5 Total 50
25
25
2 3 3 0 9(18%)
20
9
12 15 5 0
5
52
2 I
0 17(33%)
Scand J Infect Dis 7
182 O. B. Jepsen and B. Korner
Table VI. /0 fatal cases of bacteremia due to Staphylococcus aureus Pat. no.
(y.)
Sex
Infection and/or associated disease
23 35 37 40 62 68
76 69 73 79 72 67 70 55 76
F M F F F M F F M
Pyelonephritis ac., nephropathia Pneumonia Fractura colli femoris Pyarthrosis humeri Hypernephroma Diabetes, osteitis metatarsale Nephropathia acuta; anuria Strictura oesophagi, benign Ca. prostatae, urethritis suppurativa
89
69
M
Alcoholismus chronica, pneumonia
I
15 17
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Age
malignant cancer, and though many suffered from severe diseases-some being desperately ill-a substantial fraction had trivial benign diseases. DISCUSSION A positive blood culture may represent bacteremia, contamination of the sample, or both. The number of positive samples, the type of microorganism present and the growth rate and density are helpful factors in deciding which is the case (8, 13). In this study we were additionally aided by simultaneous cultures from other sites and information about antibiotic treatment at the time of blood sampling. The clinical examination of the patients revealed that the diagnosis could be made in the laboratory with fair precision provided the above-mentioned data were available. The bacteria isolated from bacteremic patients were the same as those found by Henrichsen (4) and
Procedure probably related Focus of to bacteremia infection
Acquisition of bacteremia
Nephrectomy None Osteosynthesis None None None None I.v, line Indwelling catheter None
In community
Operation wound In hospital Lungs In hospital Operation wound In hospital Joint In hospital In hospital ? In hospital Bone In hospital ? I.v. line In hospital Urethra In hospital ?
they appeared with a similar frequency. In both study groups gram-negative enteric bacteria accounted for about one half of the isolates. Coagulase-positive staphylococci were more frequent in our series, probably owing to local endemic factors. Our isolation rate of pneumococci and other streptococci was also higher than that found by Henrichsen. This may reflect a better survival of these bacteria in the samples due to our shorter line of transportation within the hospital. In Henrichsen's much larger series from 1965 and 1971 anaerobic bacteria were found in 4-5 % of the cases. No anaerobic infections occurred in our patients, but considering the size of our study group, the absence of such cases is only weakly significant. The incidence of polymicrobial growth was comparable to findings from the Mayo Clinic (17). Staphylococcal bacteremia originating from the site of intravenous infusion was found in 5 or proba-
Table VII. Seven fatal cases of bacteremia due to Proteus, Klebsiella or Enterobacter spp. UTI=urinary tract infection Pat. no.
Age (y.)
Sex
Infection and/or associated disease
2
73
M
Diabetes, UTI
5 20
69 80
F F
Pyelonephritis chronica Pyelonephritis chronica
38
79
M
Fractura colli femoris, UTI
63
62
F
67 97
66 78
F F
Choledocholithiasis, abscessus pancreatis Ca. pancreatis, peritonitis purulenta Diabetes, UTI
Scand J Infect Dis 7
Procedure probably related Focus of to bacteremia infection Indwelling catheter None Indwelling catheter Indwelling catheter None None None
Acquisition of bacteremia
Urinary tract
In hospital
? ?
In hospital In hospital
Urinary tract
In hospital
Biliary tract
In hospital
Peritoneal cavity In community Renal abscess In community
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Bacteremia in a general hospital bly 6 patients. One infection was fatal, stressing the need for revision and surveillance of this procedure (2,3,5). Gram-negative bacteremia due to enteric bacteria was almost exclusively found in patients with primary disease in the urinary or biliary tract. Infection in the urinary tract was by far the most frequent focus of bacteremia, and in two thirds of these cases the bacteremia was secondary to instrumentation of the urethra. It has long been known that manipulations within the urinary tract are associated with a high frequency of bacteremia (6, 12). Recently, this was confirmed by Sullivan et al. (15) who found a prevalence ranging from 31 % to 8 % according to the type of instrumentation. Like Watt and Okubadejo (18) we think that a disproportionate representation within the present hospital population of patients in whom such procedures are performed may account for the dominance of gram-negative bacteremia. In this context it is of interest that in 1973 a total of 28445 urethral catheters of all sorts were delivered from the central supply service in this hospital for use among approximately 30000 patients. In 1966 the corresponding figures were 16231 catheters and about 26000 patients. Owing to the obvious difficulties in comparing different groups of patients, the overall mortality of 25 % found in this material is a figure of little significance. However, staphylococcal bacteremia had a lethality of 40 %, which is the same as stated in a Danish survey of 462 cases from 1957-1960 (11). Thus, it appears that staphylococcal bacteremia, though less frequent and caused by other phage types than 15 years ago, still carries the same lethality. In the present investigation gram-negative bacteremia caused by enteric bacteria other than E. coli was fatal in 40% of cases. Bacteremia with these bacteria (proteus, klebsiella, enterobacter species) and with staphylococci was in most cases nosocomial, explaining the higher lethality in hospital-acquired bacteremia. It might be postulated that the high morbidity and lethality of nosocomial infection with these bacteria were due to serious underlying diseases in these patients. This was true in some cases, but in others the onset of bacteremia was unexpected and the fatal outcome unpredictable. The term nosocomial infection as used in this study, i.e. infection neither present nor incubating 24 hours after admission (16), does not indicate any
183
information about whether the infection was preventable. In this study one patient per 1000 admissions died with hospital-acquired bacteremia. Assuming that re-inforced prophylactic measures could reduce the lethality of nosocomial bacteremia by one tenth, 1 or 2 patients might be saved each year in this hospital alone. This study has shown that bacteria probably often resident in the hospital caused two thirds of bacteremias acquired in the hospital. This group of bacteria carried the highest lethality and was the cause of infection not only in patients suffering from severe underlying diseases, but also in patients with trivial illnesses. Attempts to reduce the frequency and mortality of bacteremia should therefore include considerations of ecological factors as well as hospital procedures likely to be followed by infections with virulent bacteria.
REFERENCES 1. Chalmers, J. P. & Tiller, D. 1.: Effect of treatment on
2. 3. 4. 5. 6. 7. 8.
9. 10. II.
12.
the mortality rate in septicaemia. Br Med J 2: 338, 1969. Darrell, J. H. & Garrod, L. P.: Secondary septicaemia from intravenous cannulae. Br MedJ 2:481, 1969. Freeman, J. B., Lemire, A. & MacLean, L. D.: Intravenous alimentation and septicemia. Surg Gynecol Obstet 135: 708, 1972. Henrichsen, J.: Recent trends of isolates from cases of bacteremia in Denmark. Scand J Infect Dis 6: 145, 1974. Hjorth, A. & Siboni, K.: Infusioner og septisk phlebitis. Nord Med 82:845, 1969. Hodgin, U. G. & Sanford, J. P.: Gram-negative rod bacteremia. An analysis of 100 patients. Am J Med 39:952, 1965. Kluge, R. M. & DuPont, H. L.: Factors affecting mortality of patients with bacteremia. Surg Gynecol Obstet 137: 267, 1973. MacGregor, R. R. & Beaty, H. N.: Evaluation of positive blood cultures. Guidelines for early differentiation of contaminated from valid positive cultures. Arch Intern Med 130: 84, 1972. McGowan, J. E., Barnes, M. W. & Finland, M.: Host-pathogen-drug interactions in surgical patients with bacteremia. Surg GynecolObstet 138: 50, 1974. Rogers, D. E., Koenig, M. G. & Holmes, K. K.: The problem of gram-negative bacteremia and its management. South MedJ 58: 1391, 1965. Rosendal, K., Faber, V., Hove, K., Jessen, O. & Eriksen, K. R.: Stafylokok-bakteriremi. IV. Bakteriologiske, epidemiologiske og kliniske iagttagelser i 462 tilftelde fra arene 1957-1960. Ugeskr Laeger 124: 459, 1962. Scott, W. W.: Bloodstream infections in urology. J Uro121: 527, 1929. Scand J Infect Dis 7
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184 O. B. Jepsen and B. Korner 13. Siboni, K.: Klinisk-bakteriologisk vurdering af bloddyrkninger med veekst. Ugeskr Laeger 124:464, 1962. 14. Siegenthaler, W., Vetter, H., Luthy. R. & Siegenthaler, G.: Klinik und antibiotische Therapie der bakteriellen septischen Erkrankungen in der inneren Medizin. Verhandlungen der Deutschen Gesellschaft fur innere Medizin, p. 805. 1. F. Bergmann, Munchen 1971. 15. Sullivan, M. M., Sutter, V. L., Mirns, M. M., Marsh, V. H. & Finegold, S. M.: Clinical aspects of bacteremia after manipulation of the genito-urinary tract. J Infect Dis 127:49,1973. 16. U.S. Department of Health, Education, and Welfare: Outline for surveillance and control of nosocomial infections. Center for Disease Control, Atlanta 1972. 17. Washington, J. A.: Comparison of two commercially available media for detection of bacteremia. Appl Microbiol22: 604, 1971. 18. Watt, P. 1. & Okubadejo, O. A.: Changes in incidence and aetiology of bacteremia arising in hospital practice. Br Med J I: 210, 1967.
Addressfor reprints: O. B. Jepsen, M.D., Department ofAntibiotics, Statens Seruminstitut, Amager Boulevard 80, DK-2300 Copenhagen S, Denmark
Scand J Infect Dis 7
