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Clinical and microbiological characteristics in cases of positive blood cultures at Shin-Kokura Hospital during a period of 5 years
J Infect Chemother (2006) 12:335–337 DOI 10.1007/s10156-006-0464-9
© Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases 2006
NOTE
Satoshi Kuboi · Hideyuki Nomura
Clinical and microbiological characteristics in cases of positive blood cultures at Shin-Kokura Hospital during a period of 5 years
Received: March 27, 2006 / Accepted: July 10, 2006
Abstract In order to evaluate the present state of bacteremia, we investigated the clinical and microbiological characteristics of positive blood culture cases hospitalized in Shin-Kokura Hospital from January 1998 through December 2002. Seventy-five cases showed positive blood cultures during the 5 years, and 48 cases (64%) were 70 years old or more. Most of the cases had underlying diseases, such as malignancy. The diagnoses of the infectious diseases found included pneumonia (9 cases), enteric infection (9 cases), hepatobiliary infection (8 cases), urinary tract infection (8 cases), and endocarditis (6 cases). A total of 102 strains of microorganism were isolated, and Gram-positive bacteria accounted for 64.7% of the cases, with Gram-negative bacteria accounting for 29.4%. Most of the isolated microorganisms showed good susceptibility to antimicrobial agents except for MRSA. Antimicrobial agents were used for 54 cases of bacteremia, and 33 patients improved, but 21 patients died, including 10 whose death was due to infection. In this study, the 54 cases of bacteremia (72% of all cases with a positive blood culture) showed a mortality rate of 18.5% due to infection, in spite of adequate antimicrobial treatment. Our data suggest that physicians should recognize the difficulty of treating bacteremia, and should pay close attention to the physical condition of patients with bacteremia. Key words Bacteremia · Antimicrobial treatment
Bacteremia is thought to be a critical disorder. A blood culture examination is often performed for cases that are suspected to have an infectious disease, but it is not easy to
S. Kuboi (*) · H. Nomura Department of Internal Medicine, Shin-Kokura Hospital, 1-3-1 Kanada, Kokurakita-ku, Kitakyushu 803-8505, Japan Tel. +81-93-571-1031; Fax +81-93-591-0553 e-mail: [email protected]
evaluate the significance of the microorganism isolated. In order to assess the present situation regarding cases of bacteremia, we retrospectively investigated the clinical and microbiological backgrounds in cases of positive blood cultures at Shin-Kokura Hospital during a 5-year period from January 1998 through December 2002. Information about each patient’s age, sex, underlying diseases, microorganism isolated, susceptibility to antimicrobial agents, antimicrobial treatment, and outcome was obtained by reviewing their medical records. Seventy-five patients had positive blood cultures, including 38 males and 37 females, and the average age was 70.6 ± 16.3 years. Forty-eight patients (64% of the total) were 70 years old or more (Table 1). Most of the patients had underlying diseases such as malignancy (23 cases, 30.7%). The diagnoses of the infectious diseases included 9 cases of pneumonia, 9 cases of enteric infection, 8 cases of hepatobiliary infection, 8 cases of urinary tract infection, and 6 cases of endocarditis. A total of 102 strains of microorganism were isolated; Gram-positive bacteria accounted for 64.7% of the cases, with Gram-negative bacteria accounting for 29.4%. The microorganism isolated most frequently was Stahylococcus aureus (19 strains, including 4 strains of MRSA), followed by Escherichia coli (16 strains), Staphylococcus epidermidis (9 strains), Enterococcus faecalis (9 strains), and Klebsiella pneumoniae (8 strains). (Table 2). Fifty-four cases (68 strains of microorganism) were diagnosed with bacteremia, and for these the isolated microorganisms were considered to be the cause of infection. Most of the isolated microorganisms showed good susceptibility to antimicrobial agents, while 4 strains of MRSA and a strain of Staphylococcus spp. were resistant to antibiotics. Antimicrobial agents were used for all 54 cases of bacteremia. The susceptibility of the isolated microorganisms to the initial antimicrobial agents was generally good, and 33 cases of bacteremia improved, but 21 patients died (Table 3). Of the 10 cases that were considered to have died of infection, 8 cases had malignancy, and drug-resistant bacteria, including 2 strains of MRSA and a strain of Enterococcus casseliflavus, were isolated in 3 cases.
336
Among the hospitalized patients who showed a positive blood culture at Shin-Kokura Hospital, the proportion of elderly people was high. Most of the patients had underlying diseases such as malignancy. The rate of complications with bacteremia has been reported to be high in elderly people due to a decrease in their immune defense mechanisms resulting from hyponutrition and associated underlying diseases.1 The five major pathogens reported to have been found in positive blood cultures are Staphylococcus aureus, Escherichia coli, coagulase-negative staphylococcus (CNS), Klebsiella pneumoniae, and Enterococcus species.2 Our data also
Gram-positive bacteria
No. of isolated strains
(18.6) (8.8) (8.8) (7.8) (4.9) (4.9) (2.9) (2.0) (2.0) (1.0) (1.0) (1.0) (1.0)
27 (36.0) 48 (64.0) 70.6 ± 16.3 years
Subtotal
66
(64.7)
23 (30.7) 9 (12.0) 8 (10.7) 6 (8.0) 8 (10.7) 5 (6.7) 5 (6.7) 3 (4.0) 2 (2.7) 5 (6.7) 1 (1.3)
Escherichia coli Klebsiella pneumoniae Aeromonas hydrophila Citrobacter diversus Haemophilus influenzae Proteus vulgaris Salmonella typhimurium Serratia marcescens
16 8 1 1 1 1 1 1
(15.7) (7.8) (1.0) (1.0) (1.0) (1.0) (1.0) (1.0)
Subtotal
30
(29.4)
9 (14.5) 9 (14.5) 8 (12.9) 8 (12.9) 6 (9.6) 5 (8.1) 2 (3.2) 2 (3.2) 13 (21.0) 13 (21.0)
Bacteroides fragilis
38 (50.7) 37 (49.3)
Gram-negative bacteria
Anaerobes
No. of isolated strains
No. of isolated strains 5
Fungus
No. of isolated strains
Cryptococcus neoformans Total
(%)
(%) (4.9) (%)
1
(1.0)
102
(100)
MSSA, methicillin-susceptible Staphylococcus aureus; MRSA, methicillin-resistant Staphylococcus aureus; PSSP, penicillin-susceptible Streptococcus pneumoniae; PRSP, penicillin-resistant Streptococcus pneumoniae
Table 3. Susceptibility to antimicrobial agents and outcome for 54 patients with bacteremia Initial antimicrobial agents
(%)
19 (MSSA 15, MRSA 4) 9 9 8 5 5 3 (PSSP 1, PRSP 2) 2 2 1 1 1 1
No. of patients (%)
Sex Male Female Age Under 70 years 70 Years or more Mean age ± SD Underlying disease Malignancy Hepatobiliary disease Cerebrovascular disease Cardiovalvular disease Other cardiac disease Genitourinary disease Diabetes mellitus Vertebral disease Respiratory disease Others No underlying disease Infectious disease Pneumonia Enteric infection Biliary tract infection Urinary tract infection Endocarditis Dermal infection Intrapelvic infection Central venous catheter infection Other infectious disease No infectious disease
Table 2. Details of microorganisms isolated
Staphylococcus aureus Streptococcus epidermidis Enterococcus faecalis Staphylococcus spp. Bacillus cereus Bacillus spp. Streptococcus pneumoniae Streptococcus constellatus Streptococcus equisimilis Enterococcus casseliflavus Streptococcus agalactiae Streptococcus mitis Streptococcus spp.
Table 1. Clinical characteristics of the 75 cases with positive blood cultures Characteristics
showed that these five species of bacteria were in the majority. It has previously been reported that Gram-negative bacteria were more commonly isolated from blood cultures,3,4 but recent reports have indicated that Grampositive bacteria have been isolated more frequently.5–7 Our data also showed a similar trend of increasing Gram-
Antimicrobial susceptibility
Total
Outcome
S
R
ND
Penicillins Cephems Carbapenems Aminoglycosides Tetracyclines Macrolides Quinolones Fosfomycin Vancomycin
3 14 9 0 2 0 0 0 1
0 2 4 0 1 0 0 0 0
0 9 6 1 0 1 0 1 0
3 25 19 1 3 1 0 1 1
2 17 10 0 2 1 0 1 0
1 8 9 1 1 0 0 0 1
Total
29
7
18
54
33
21
S, susceptible; R, resistant; ND, not done
Improved
Died
337
positive bacteria, with the proportion of Gram-positive bacteria being as high as 64.7% of all the isolates. It has been reported that leading identifiable sources of these infections have included intravenous catheters, the respiratory and genitourinary tracts, and intraabdominal foci.2 However, our data showed that many cases of positive blood cultures were associated with pneumonia, enteric infection, biliary tract infection, urinary tract infection, and endocarditis, but only three cases were related to intravenous catheter infection. Of the 54 cases that were diagnosed with bacteremia, 10 cases (18.5% of all the bacteremia cases) died due to infectious diseases in spite of adequate antimicrobial treatment. Most of the patients who died had a malignancy and/or a drug-resistant microorganism. It has been reported that severely ill patients have a tendency to develop bacteremia. The reported frequency of bacteremia in patients with severe pneumonia varies from as low as 4% to as high as 18%.8,9 The mortality rate of severely ill septic patients is reported to be 20%–50%.10,11 Weinstein et al.2 reported that the mortality rate was 13.3% even in patients who received appropriate antimicrobial therapy throughout the course of the infection. Our results also showed that a surprisingly high proportion of patients died in spite of the good susceptibility of the isolated microorganisms to the antimicrobial agents used. A multivariate analysis report showed that the factors which independently influenced the outcome of bacteremia were age, microorganism, source of infection, predisposing factors, blood pressure, body temperature, and therapy.2 The fact that some patients with predisposing problems received no benefit from infection therapy in spite of an adequate use of antimicrobial agents suggests that the condition of the immune defense mechanism is an important factor for the outcome of bacteremia. Our study has suggested that it is still difficult to treat bacteremia in severely ill patients with conditions such as
malignancy in spite of the isolation of the drug-resistant bacteria. Physicians should pay close attention to the physical condition of patients who are suspected to have bacteremia.
References 1. Hara K, Shiozawa T, Kohno S, Kadota J, Shirai R, Kawakami K, et al. Complication of infection in malnutritional status. Kansenshogaku Zasshi 1998;72:569–74. 2. Weinstein MP, Towns ML, Quartey SM, Mirrett S, Reimer LG, Parmigiani G, et al. The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults. Clin Infect Dis 1997;24:584–602. 3. Sonnenblick M, Carmon M, Rudenski B, Friedlander Y, Van Oijk JM. Septicemia in the elderly: incidence, etiology and prognostic factors. Isr J Med Sci 1990;26:195–9. 4. Meyers BR, Sherman E, Mendelson MH, Velasquez G, SrulevitchChin E, Hubbard M, et al. Bloodstream infections in the elderly. Am J Med 1989;86:379–84. 5. Konishi M, Mori K, Majima T, Ueda K, Teramoto S, Sakamoto M, et al. Clinical analysis of patients with sepsis: comparison between underlying diseases. Kansenshogaku Zasshi 1998;72:681– 7. 6. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003;348:1546–54. 7. Friedman G, Silva E, Vincent JL. Has the mortality of septic shock changed with time? Crit Care Med 1998;26:2078–86. 8. Skerrett SJ. Diagnostic testing for community-acquired pneumonia. Clin Chest Med 1999;20:531–48. 9. El-Sohl AA, Sikka P, Ramadan F, Davis J. Etiology of severe pneumonia in the very elderly. Am J Respir Crit Care Med 2001;163:645–51. 10. Aoki Y, Fukuoka M, Kusaba K, Tanabe I, Nagasawa Z, Tominaga M, et al. Current practice of management of bacteremic sepsis: a study in a tertiary care teaching hospital in Japan. Intern Med 2000;39:901–9. 11. Wheeler AP, Bernard GR. Treating patients with severe sepsis. N Engl J Med 1999;340:207–14.
© Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases 2006
NOTE
Satoshi Kuboi · Hideyuki Nomura
Clinical and microbiological characteristics in cases of positive blood cultures at Shin-Kokura Hospital during a period of 5 years
Received: March 27, 2006 / Accepted: July 10, 2006
Abstract In order to evaluate the present state of bacteremia, we investigated the clinical and microbiological characteristics of positive blood culture cases hospitalized in Shin-Kokura Hospital from January 1998 through December 2002. Seventy-five cases showed positive blood cultures during the 5 years, and 48 cases (64%) were 70 years old or more. Most of the cases had underlying diseases, such as malignancy. The diagnoses of the infectious diseases found included pneumonia (9 cases), enteric infection (9 cases), hepatobiliary infection (8 cases), urinary tract infection (8 cases), and endocarditis (6 cases). A total of 102 strains of microorganism were isolated, and Gram-positive bacteria accounted for 64.7% of the cases, with Gram-negative bacteria accounting for 29.4%. Most of the isolated microorganisms showed good susceptibility to antimicrobial agents except for MRSA. Antimicrobial agents were used for 54 cases of bacteremia, and 33 patients improved, but 21 patients died, including 10 whose death was due to infection. In this study, the 54 cases of bacteremia (72% of all cases with a positive blood culture) showed a mortality rate of 18.5% due to infection, in spite of adequate antimicrobial treatment. Our data suggest that physicians should recognize the difficulty of treating bacteremia, and should pay close attention to the physical condition of patients with bacteremia. Key words Bacteremia · Antimicrobial treatment
Bacteremia is thought to be a critical disorder. A blood culture examination is often performed for cases that are suspected to have an infectious disease, but it is not easy to
S. Kuboi (*) · H. Nomura Department of Internal Medicine, Shin-Kokura Hospital, 1-3-1 Kanada, Kokurakita-ku, Kitakyushu 803-8505, Japan Tel. +81-93-571-1031; Fax +81-93-591-0553 e-mail: [email protected]
evaluate the significance of the microorganism isolated. In order to assess the present situation regarding cases of bacteremia, we retrospectively investigated the clinical and microbiological backgrounds in cases of positive blood cultures at Shin-Kokura Hospital during a 5-year period from January 1998 through December 2002. Information about each patient’s age, sex, underlying diseases, microorganism isolated, susceptibility to antimicrobial agents, antimicrobial treatment, and outcome was obtained by reviewing their medical records. Seventy-five patients had positive blood cultures, including 38 males and 37 females, and the average age was 70.6 ± 16.3 years. Forty-eight patients (64% of the total) were 70 years old or more (Table 1). Most of the patients had underlying diseases such as malignancy (23 cases, 30.7%). The diagnoses of the infectious diseases included 9 cases of pneumonia, 9 cases of enteric infection, 8 cases of hepatobiliary infection, 8 cases of urinary tract infection, and 6 cases of endocarditis. A total of 102 strains of microorganism were isolated; Gram-positive bacteria accounted for 64.7% of the cases, with Gram-negative bacteria accounting for 29.4%. The microorganism isolated most frequently was Stahylococcus aureus (19 strains, including 4 strains of MRSA), followed by Escherichia coli (16 strains), Staphylococcus epidermidis (9 strains), Enterococcus faecalis (9 strains), and Klebsiella pneumoniae (8 strains). (Table 2). Fifty-four cases (68 strains of microorganism) were diagnosed with bacteremia, and for these the isolated microorganisms were considered to be the cause of infection. Most of the isolated microorganisms showed good susceptibility to antimicrobial agents, while 4 strains of MRSA and a strain of Staphylococcus spp. were resistant to antibiotics. Antimicrobial agents were used for all 54 cases of bacteremia. The susceptibility of the isolated microorganisms to the initial antimicrobial agents was generally good, and 33 cases of bacteremia improved, but 21 patients died (Table 3). Of the 10 cases that were considered to have died of infection, 8 cases had malignancy, and drug-resistant bacteria, including 2 strains of MRSA and a strain of Enterococcus casseliflavus, were isolated in 3 cases.
336
Among the hospitalized patients who showed a positive blood culture at Shin-Kokura Hospital, the proportion of elderly people was high. Most of the patients had underlying diseases such as malignancy. The rate of complications with bacteremia has been reported to be high in elderly people due to a decrease in their immune defense mechanisms resulting from hyponutrition and associated underlying diseases.1 The five major pathogens reported to have been found in positive blood cultures are Staphylococcus aureus, Escherichia coli, coagulase-negative staphylococcus (CNS), Klebsiella pneumoniae, and Enterococcus species.2 Our data also
Gram-positive bacteria
No. of isolated strains
(18.6) (8.8) (8.8) (7.8) (4.9) (4.9) (2.9) (2.0) (2.0) (1.0) (1.0) (1.0) (1.0)
27 (36.0) 48 (64.0) 70.6 ± 16.3 years
Subtotal
66
(64.7)
23 (30.7) 9 (12.0) 8 (10.7) 6 (8.0) 8 (10.7) 5 (6.7) 5 (6.7) 3 (4.0) 2 (2.7) 5 (6.7) 1 (1.3)
Escherichia coli Klebsiella pneumoniae Aeromonas hydrophila Citrobacter diversus Haemophilus influenzae Proteus vulgaris Salmonella typhimurium Serratia marcescens
16 8 1 1 1 1 1 1
(15.7) (7.8) (1.0) (1.0) (1.0) (1.0) (1.0) (1.0)
Subtotal
30
(29.4)
9 (14.5) 9 (14.5) 8 (12.9) 8 (12.9) 6 (9.6) 5 (8.1) 2 (3.2) 2 (3.2) 13 (21.0) 13 (21.0)
Bacteroides fragilis
38 (50.7) 37 (49.3)
Gram-negative bacteria
Anaerobes
No. of isolated strains
No. of isolated strains 5
Fungus
No. of isolated strains
Cryptococcus neoformans Total
(%)
(%) (4.9) (%)
1
(1.0)
102
(100)
MSSA, methicillin-susceptible Staphylococcus aureus; MRSA, methicillin-resistant Staphylococcus aureus; PSSP, penicillin-susceptible Streptococcus pneumoniae; PRSP, penicillin-resistant Streptococcus pneumoniae
Table 3. Susceptibility to antimicrobial agents and outcome for 54 patients with bacteremia Initial antimicrobial agents
(%)
19 (MSSA 15, MRSA 4) 9 9 8 5 5 3 (PSSP 1, PRSP 2) 2 2 1 1 1 1
No. of patients (%)
Sex Male Female Age Under 70 years 70 Years or more Mean age ± SD Underlying disease Malignancy Hepatobiliary disease Cerebrovascular disease Cardiovalvular disease Other cardiac disease Genitourinary disease Diabetes mellitus Vertebral disease Respiratory disease Others No underlying disease Infectious disease Pneumonia Enteric infection Biliary tract infection Urinary tract infection Endocarditis Dermal infection Intrapelvic infection Central venous catheter infection Other infectious disease No infectious disease
Table 2. Details of microorganisms isolated
Staphylococcus aureus Streptococcus epidermidis Enterococcus faecalis Staphylococcus spp. Bacillus cereus Bacillus spp. Streptococcus pneumoniae Streptococcus constellatus Streptococcus equisimilis Enterococcus casseliflavus Streptococcus agalactiae Streptococcus mitis Streptococcus spp.
Table 1. Clinical characteristics of the 75 cases with positive blood cultures Characteristics
showed that these five species of bacteria were in the majority. It has previously been reported that Gram-negative bacteria were more commonly isolated from blood cultures,3,4 but recent reports have indicated that Grampositive bacteria have been isolated more frequently.5–7 Our data also showed a similar trend of increasing Gram-
Antimicrobial susceptibility
Total
Outcome
S
R
ND
Penicillins Cephems Carbapenems Aminoglycosides Tetracyclines Macrolides Quinolones Fosfomycin Vancomycin
3 14 9 0 2 0 0 0 1
0 2 4 0 1 0 0 0 0
0 9 6 1 0 1 0 1 0
3 25 19 1 3 1 0 1 1
2 17 10 0 2 1 0 1 0
1 8 9 1 1 0 0 0 1
Total
29
7
18
54
33
21
S, susceptible; R, resistant; ND, not done
Improved
Died
337
positive bacteria, with the proportion of Gram-positive bacteria being as high as 64.7% of all the isolates. It has been reported that leading identifiable sources of these infections have included intravenous catheters, the respiratory and genitourinary tracts, and intraabdominal foci.2 However, our data showed that many cases of positive blood cultures were associated with pneumonia, enteric infection, biliary tract infection, urinary tract infection, and endocarditis, but only three cases were related to intravenous catheter infection. Of the 54 cases that were diagnosed with bacteremia, 10 cases (18.5% of all the bacteremia cases) died due to infectious diseases in spite of adequate antimicrobial treatment. Most of the patients who died had a malignancy and/or a drug-resistant microorganism. It has been reported that severely ill patients have a tendency to develop bacteremia. The reported frequency of bacteremia in patients with severe pneumonia varies from as low as 4% to as high as 18%.8,9 The mortality rate of severely ill septic patients is reported to be 20%–50%.10,11 Weinstein et al.2 reported that the mortality rate was 13.3% even in patients who received appropriate antimicrobial therapy throughout the course of the infection. Our results also showed that a surprisingly high proportion of patients died in spite of the good susceptibility of the isolated microorganisms to the antimicrobial agents used. A multivariate analysis report showed that the factors which independently influenced the outcome of bacteremia were age, microorganism, source of infection, predisposing factors, blood pressure, body temperature, and therapy.2 The fact that some patients with predisposing problems received no benefit from infection therapy in spite of an adequate use of antimicrobial agents suggests that the condition of the immune defense mechanism is an important factor for the outcome of bacteremia. Our study has suggested that it is still difficult to treat bacteremia in severely ill patients with conditions such as
malignancy in spite of the isolation of the drug-resistant bacteria. Physicians should pay close attention to the physical condition of patients who are suspected to have bacteremia.
References 1. Hara K, Shiozawa T, Kohno S, Kadota J, Shirai R, Kawakami K, et al. Complication of infection in malnutritional status. Kansenshogaku Zasshi 1998;72:569–74. 2. Weinstein MP, Towns ML, Quartey SM, Mirrett S, Reimer LG, Parmigiani G, et al. The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults. Clin Infect Dis 1997;24:584–602. 3. Sonnenblick M, Carmon M, Rudenski B, Friedlander Y, Van Oijk JM. Septicemia in the elderly: incidence, etiology and prognostic factors. Isr J Med Sci 1990;26:195–9. 4. Meyers BR, Sherman E, Mendelson MH, Velasquez G, SrulevitchChin E, Hubbard M, et al. Bloodstream infections in the elderly. Am J Med 1989;86:379–84. 5. Konishi M, Mori K, Majima T, Ueda K, Teramoto S, Sakamoto M, et al. Clinical analysis of patients with sepsis: comparison between underlying diseases. Kansenshogaku Zasshi 1998;72:681– 7. 6. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003;348:1546–54. 7. Friedman G, Silva E, Vincent JL. Has the mortality of septic shock changed with time? Crit Care Med 1998;26:2078–86. 8. Skerrett SJ. Diagnostic testing for community-acquired pneumonia. Clin Chest Med 1999;20:531–48. 9. El-Sohl AA, Sikka P, Ramadan F, Davis J. Etiology of severe pneumonia in the very elderly. Am J Respir Crit Care Med 2001;163:645–51. 10. Aoki Y, Fukuoka M, Kusaba K, Tanabe I, Nagasawa Z, Tominaga M, et al. Current practice of management of bacteremic sepsis: a study in a tertiary care teaching hospital in Japan. Intern Med 2000;39:901–9. 11. Wheeler AP, Bernard GR. Treating patients with severe sepsis. N Engl J Med 1999;340:207–14.