Article
Vol. 11. No. 5
403
Eur. J. Clin. Microbiol. Infect. Dis., May 1992, p. 403--407 0934-9723/92/05 0403-05 $ 3.00/0
Value of Differential Quantitative Blood Cultures in the Diagnosis of Catheter-Related Sepsis
J.A. C a p d e v i l a l . , A . M . P l a n e s 2, M. P a l o m a r 3, I. G a s s e r 2, B. A l m i r a n t e 1, A . P a h i s s a 1, E. C r e s p o 2, J.M. M a r t f n e z - V f i z q u e z 1
A prospective study was performed to assess the value of differential quantitative blood cultures in the diagnosis of catheter-related sepsis when this condition is suspected on clinical grounds and to establish a reliable discriminative value for application without removal of the inserted catheter. A total of 107 central venous catheters from 64 patients were used for the study. Blood was obtained simultaneously through the suspected infected device dnd from a peripheral venipuncture. The catheter was removed and its tip cultured semiquantitatively. Catheter-related sepsis occurred in 17 patients. Using as cut-off value a colony count fourfold higher in blood drawn through the catheter than in simultaneously drawn peripheral blood, a sensitivity of 94 %, specificity of 100 % and positive predictive value of 100 % were obtained. A single bacterial count > 100 cfu/ml in the quantitative culture of the catheter blood specimen in the presence of a positive qualitative peripheral blood culture of the same organism was also highly suggestive of catheter-related sepsis. Differential quantitative blood culture is a reliable method for the diagnosis of catheter-associated sepsis without catheter removal.
Catheter-related' infection is a major cause of nosocomial bacteremia (1). A positive culture of the catheter tip confirms the diagnosis. However, systematic withdrawal and culture of implicated catheters yields negative results in between 75 % and 85 % of cases (2). In addition, various studies have now shown that some of these infections can be cured by antibiotic treatment alone without catheter removal (3, 4). However, in all patients with vascular access infection caused by yeasts the catheters should be removed as the first step in therapy (4). Quantitative blood culture by a pour-plate technique was introduced in 1979 by Wing et al. (5) for use in the diagnosis of catheter sepsis. The increased bacterial colony counts in blood drawn through the catheter compared to blood drawn from a peripheral vein is considered by many investigators to be a useful m e t h o d for diagnosing catheter-related bacteremia (4, 6-16). However, there are conflicting results regarding sensitivity and specificity of the method (13, 17) and the selection of the lower limit of colony
1Department of Internal Medicine-Infectious Diseases, 2Department of Microbiology, and 3Intensive Care Unit, Hospital Vail d'Hebr6n, Autonomous University of Barcelona, 08035 Barcelona, Spain.
counts for defining colonization. The purpose of this prospective study was to assess the value of differential quantitative blood culture in the diagnosis of catheter-related sepsis and to establish a reliable discriminative value for application without removal of the inserted catheter.
Materials and Methods
Patients. During a 17-month period (April 1988 to August 1989) patients with vascular catheters suspected as being the primary source of catheter-related sepsis were studied prospectively. The study was carried out in an 850-bed university hospital in patients hospitalized in internal medicine and surgery wards, and intensive care units. Catheter-related sepsis was suspected when a patient in whom one or more vascular catheters had been inserted developed fever and/or clinical signs of sepsis in the absence of documented infection. Details of the type and number of catheters used, insertion sites and dates of insertion were recorded as well as patients' age and sex, hospitalization period, underlying disease, clinical condition at the time of the study, and antibiotic treatment in the previous 48 hours.
Microbiological h~vestigations. Blood cultures included the following: two qualitative cultures (Bactec NR 660, Becton Dickinson, USA) of blood samples taken 15 min
404
apart and a quantitative culture of blood obtained from a peripheral vein by standard venipuneture; quantitative culture of blood obtained through the suspected catheter; and culture of the distal 3 to 4 cm of the catheter after removal by the semiquantitative method proposed by Maki et al. (18). A volume of 7 to 10 ml of blood was collected for each blood culture. The quantitative blood culture was carried out by the pour-plate technique in which blood was mixed with 80 ml of brain-heart infusion agar and poured into petri dishes. Colony forming units (cfu) were counted; when growth was considered confluent the result was expressed as > 1000 cfu/ml. Each intravaseular device was removed aseptically after the area of insertion was washed with povidone-iodine solution. In the case of a negative semiquantitative catheter tip culture and positive quantitative catheter blood culture, the catheter was cultured on Tryptiease soy broth 24 to 48 hours later. The catheter tip culture was considered positive when bacterial growth was observed on semiquantitative culture or on the Trypticase soy broth cultm'e. Identification and antimicrobial susceptibility testing of microorganisms were carried out using either standard procedures or an automatized system (AMS-Vitek, McDonell Douglas, USA). The microorganisms isolated were considered to be identical when genus, species, biotype and antibiotic susceptibility pattern coincided.
Interpretation of Results. A catheter-related sepsis was considered to exist when the same organism was isolated from the catheter tip and one or more peripheral blood samples, no primary infective site other than the central venous catheter could be identified clinically or bacteriologically, and the patient recovered after removal of the catheter. Sepsis was classified as unrelated to the presence of intravenous catheters when one or more peripheral blood cultures were positive, culture of the catheter tip was negative, an alternative site of infection was identified and/or the patient did not recover after removal of the catheter. Colonization and/or infection of the catheter without sepsis was considered to exist when culture of the catheter tip was positive and all peripheral blood cultures were negative. When growth was obtained from a peripheral blood culture only and the quantitative peripheral blood cultm'e was negative, the count was expressed as < 1 cfu/mI. The sensitivity, specificity, and predictive values of positive and negative results were calculated at different levels of differential colony counts between quantitative catheter and peripheral blood cultures. In addition, a single bacterial count > 100 cfu/ml in the quantitative culture of the catheter blood specimen was used as a criterion for diagnosis of catheter-related sepsis in a patient without a quantitative peripheral venous blood culture.
Eur. J. Clin. Microbiol. Infect. Dis.
femoral (11) or radial (4) arteries. T h e m e a n n u m b e r of catheters inserted per patient and febrile episode was 1.6 (range 1 to 5). Catheters remained in situ for a m e a n of 13 days (range 1 to 65). Eighty (75 % ) catheters were r e c o v e r e d from patients treated with antibiotics 48 hours prior to the study. Catheter-related sepsis occurred in 17 patients (Table 1). In these patients catheters r e m a i n e d in situ for a m e a n of 19 days (range 3-65). In all but one patient (case no. 14) bacterial counts obtained via the catheter were fourfold or m o r e higher than the counts in the peripheral blood specimen, yielding > 100 cfu/ml in most cases. Differential colony counts allowed the diagnosis of catheter-related sepsis in four patients with m o r e than o n e simultaneously inserted catheter (cases no, 1 to 4). T h e bacterial species distribution showed a p r e d o m i n a n c e of Staphylococcus" epidermidis. Eleven of the 17 patients were given antibiotics at the time of the study. Antibiotics given were b r o a d - s p e c t r u m beta-lactam (mostly cephalosporins) without in vitro activity against the isolated microorganisms. A colonized and/or infected catheter tip with sterile peripheral blood cultures was found in 13 patients (Table 2). Sepsis not related to intravenous catheters occurred in seven patients (Table 2). On three occasions the only positive cultures were those of blood drawn through the intravascular device; these were interpreted as contamination in the collection and/or processing of the samples, or as colonization or infection of the hub itself without colonization of the tip. Using as cut-off value a fourfold higher bacterial colony count in blood drawn through the catheter c o m p a r e d to simultaneously drawn peripheral blood, a sensitivity of 94 %, specificity o f 100 % and positive predictive value of 100 % were obtained. Using a cut-off value of > 100 cfu/ml, the sensitivity and specificity of an isolated quantitative catheter blood culture were 82 % and 100 %, respectively.
Discussion Results A total of 107 vascular catheters from 64 patients with 67 febrile episodes were used for the study. These included 92 central venous catheters (36 subclavian, 16 internal jugular, 28 basilic, 10 femoral, 2 axillary) and 15 catheters placed in the
This study d e m o n s t r a t e s that differential quantitative blood culture is a useful technique for diagnosing catheter-related sepsis. Using this technique it is possible to diagnose or exclude catheter sepsis without catheter r e m o v a l when catheter-related sepsis is suspected clinically. A fourfold or greater difference in bacterial colony
Vo1.11,1992
405
Table 1: Comparison of results of paired quantitative cultures of peripheral venous blood and catheter blood, and semiquantitative culture of catheter tips in 17 patients with catheter-related sepsis and 22 cathetel~ inserted. O r g a n i s m count (efu/ml) Case no,
5 6 7 8 9 10 11 12 13 14 t5 16 17
Organism Peripheral blood
Staphylococcus epidermidis Staphylococcus epidermidis* Staphylococcus epidermidis* Staphylococcus epidermidis Staphylococcus epidermidis* Staphylococcus epidermidis Staphylococcus epidermidis* Staphylococcus epidermidis Staphylococcus epidermidis* Pseudomonas aerughzosa Staphylococcus epidermidis Staphy'lococcus epidermidis Torulopsisglabrata Staphylococcus epidermidk Staphylococcus epidermidis Staphylococcus epidermidis Staphylococcus epidermidis Staphylococcus epidermidis Staphylococcus epidermidis Staphylococcus aureus Pseudomonas aeruginosa Staphylococcus epidermidis
45 45 45 5 5 40 40 1000 0 > 1000 > 1000 1000 > 1000 500 > 1000 13 > 10130
1
> 10ft)
26 90 5 8
18 500 20 > 1000
C a t h e t e r tip > 1000 0 0 > 1000 0 13 0 > 40 0 > 1000 > 1000 + broth > 1000 15 11 + broth > 1000 > 100 > 100 > 100 > 15 9
*No source of sepsis. Table 2: Comparison of results of paired quantitative cultures of peripheral venous blood and catheter blood, and semiquantitative culture of catheter tips in 13 patients with colonized and/or infected catheters (no, 1-13), and in 7 patients with sepsis unrelated to intravenous catheters (no. 14-20). Organism count (cfu/ml) Case no.
1 2 3 4 5 6 7 8 9 10
11 12 13 14 15" 16" 17 18 19* 20
Organism Peripheral blood
C a t h e t e r blood
C a t h e t e r tip
Staphflococcus epidermidb Staphylococcusepidermidb Staphylococcusepidermidis Staphylococcusepidermidis Staphylococcusepidermidis Staphylococcusepidermidb Staphylococcusepidermidis Staphylococcusepidermidis Klebsiellapneumoniae Streptococcusfaecal& Staphylococcusepidermidis Staphylococcusepidermidis Staphylococcusepidermidis
0 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 8 50 0 0 0 20 500 1 0 0
>50 > I00 > 100 > 100 > 100 16 10 > 1000 + broth + broth 45 > 100 4
Pseudomonasaeruginosa Staphylococcusepidermidis Staphylococcus epidermidis Enterobactercloacae Enterobacter cloacae Staphylococcusepidermidis Pseudomonasaeruginosa Staphylococcus epidermidis Staphylococcus epidermidb Candidaalbkans
Vol. 11. No. 5
403
Eur. J. Clin. Microbiol. Infect. Dis., May 1992, p. 403--407 0934-9723/92/05 0403-05 $ 3.00/0
Value of Differential Quantitative Blood Cultures in the Diagnosis of Catheter-Related Sepsis
J.A. C a p d e v i l a l . , A . M . P l a n e s 2, M. P a l o m a r 3, I. G a s s e r 2, B. A l m i r a n t e 1, A . P a h i s s a 1, E. C r e s p o 2, J.M. M a r t f n e z - V f i z q u e z 1
A prospective study was performed to assess the value of differential quantitative blood cultures in the diagnosis of catheter-related sepsis when this condition is suspected on clinical grounds and to establish a reliable discriminative value for application without removal of the inserted catheter. A total of 107 central venous catheters from 64 patients were used for the study. Blood was obtained simultaneously through the suspected infected device dnd from a peripheral venipuncture. The catheter was removed and its tip cultured semiquantitatively. Catheter-related sepsis occurred in 17 patients. Using as cut-off value a colony count fourfold higher in blood drawn through the catheter than in simultaneously drawn peripheral blood, a sensitivity of 94 %, specificity of 100 % and positive predictive value of 100 % were obtained. A single bacterial count > 100 cfu/ml in the quantitative culture of the catheter blood specimen in the presence of a positive qualitative peripheral blood culture of the same organism was also highly suggestive of catheter-related sepsis. Differential quantitative blood culture is a reliable method for the diagnosis of catheter-associated sepsis without catheter removal.
Catheter-related' infection is a major cause of nosocomial bacteremia (1). A positive culture of the catheter tip confirms the diagnosis. However, systematic withdrawal and culture of implicated catheters yields negative results in between 75 % and 85 % of cases (2). In addition, various studies have now shown that some of these infections can be cured by antibiotic treatment alone without catheter removal (3, 4). However, in all patients with vascular access infection caused by yeasts the catheters should be removed as the first step in therapy (4). Quantitative blood culture by a pour-plate technique was introduced in 1979 by Wing et al. (5) for use in the diagnosis of catheter sepsis. The increased bacterial colony counts in blood drawn through the catheter compared to blood drawn from a peripheral vein is considered by many investigators to be a useful m e t h o d for diagnosing catheter-related bacteremia (4, 6-16). However, there are conflicting results regarding sensitivity and specificity of the method (13, 17) and the selection of the lower limit of colony
1Department of Internal Medicine-Infectious Diseases, 2Department of Microbiology, and 3Intensive Care Unit, Hospital Vail d'Hebr6n, Autonomous University of Barcelona, 08035 Barcelona, Spain.
counts for defining colonization. The purpose of this prospective study was to assess the value of differential quantitative blood culture in the diagnosis of catheter-related sepsis and to establish a reliable discriminative value for application without removal of the inserted catheter.
Materials and Methods
Patients. During a 17-month period (April 1988 to August 1989) patients with vascular catheters suspected as being the primary source of catheter-related sepsis were studied prospectively. The study was carried out in an 850-bed university hospital in patients hospitalized in internal medicine and surgery wards, and intensive care units. Catheter-related sepsis was suspected when a patient in whom one or more vascular catheters had been inserted developed fever and/or clinical signs of sepsis in the absence of documented infection. Details of the type and number of catheters used, insertion sites and dates of insertion were recorded as well as patients' age and sex, hospitalization period, underlying disease, clinical condition at the time of the study, and antibiotic treatment in the previous 48 hours.
Microbiological h~vestigations. Blood cultures included the following: two qualitative cultures (Bactec NR 660, Becton Dickinson, USA) of blood samples taken 15 min
404
apart and a quantitative culture of blood obtained from a peripheral vein by standard venipuneture; quantitative culture of blood obtained through the suspected catheter; and culture of the distal 3 to 4 cm of the catheter after removal by the semiquantitative method proposed by Maki et al. (18). A volume of 7 to 10 ml of blood was collected for each blood culture. The quantitative blood culture was carried out by the pour-plate technique in which blood was mixed with 80 ml of brain-heart infusion agar and poured into petri dishes. Colony forming units (cfu) were counted; when growth was considered confluent the result was expressed as > 1000 cfu/ml. Each intravaseular device was removed aseptically after the area of insertion was washed with povidone-iodine solution. In the case of a negative semiquantitative catheter tip culture and positive quantitative catheter blood culture, the catheter was cultured on Tryptiease soy broth 24 to 48 hours later. The catheter tip culture was considered positive when bacterial growth was observed on semiquantitative culture or on the Trypticase soy broth cultm'e. Identification and antimicrobial susceptibility testing of microorganisms were carried out using either standard procedures or an automatized system (AMS-Vitek, McDonell Douglas, USA). The microorganisms isolated were considered to be identical when genus, species, biotype and antibiotic susceptibility pattern coincided.
Interpretation of Results. A catheter-related sepsis was considered to exist when the same organism was isolated from the catheter tip and one or more peripheral blood samples, no primary infective site other than the central venous catheter could be identified clinically or bacteriologically, and the patient recovered after removal of the catheter. Sepsis was classified as unrelated to the presence of intravenous catheters when one or more peripheral blood cultures were positive, culture of the catheter tip was negative, an alternative site of infection was identified and/or the patient did not recover after removal of the catheter. Colonization and/or infection of the catheter without sepsis was considered to exist when culture of the catheter tip was positive and all peripheral blood cultures were negative. When growth was obtained from a peripheral blood culture only and the quantitative peripheral blood cultm'e was negative, the count was expressed as < 1 cfu/mI. The sensitivity, specificity, and predictive values of positive and negative results were calculated at different levels of differential colony counts between quantitative catheter and peripheral blood cultures. In addition, a single bacterial count > 100 cfu/ml in the quantitative culture of the catheter blood specimen was used as a criterion for diagnosis of catheter-related sepsis in a patient without a quantitative peripheral venous blood culture.
Eur. J. Clin. Microbiol. Infect. Dis.
femoral (11) or radial (4) arteries. T h e m e a n n u m b e r of catheters inserted per patient and febrile episode was 1.6 (range 1 to 5). Catheters remained in situ for a m e a n of 13 days (range 1 to 65). Eighty (75 % ) catheters were r e c o v e r e d from patients treated with antibiotics 48 hours prior to the study. Catheter-related sepsis occurred in 17 patients (Table 1). In these patients catheters r e m a i n e d in situ for a m e a n of 19 days (range 3-65). In all but one patient (case no. 14) bacterial counts obtained via the catheter were fourfold or m o r e higher than the counts in the peripheral blood specimen, yielding > 100 cfu/ml in most cases. Differential colony counts allowed the diagnosis of catheter-related sepsis in four patients with m o r e than o n e simultaneously inserted catheter (cases no, 1 to 4). T h e bacterial species distribution showed a p r e d o m i n a n c e of Staphylococcus" epidermidis. Eleven of the 17 patients were given antibiotics at the time of the study. Antibiotics given were b r o a d - s p e c t r u m beta-lactam (mostly cephalosporins) without in vitro activity against the isolated microorganisms. A colonized and/or infected catheter tip with sterile peripheral blood cultures was found in 13 patients (Table 2). Sepsis not related to intravenous catheters occurred in seven patients (Table 2). On three occasions the only positive cultures were those of blood drawn through the intravascular device; these were interpreted as contamination in the collection and/or processing of the samples, or as colonization or infection of the hub itself without colonization of the tip. Using as cut-off value a fourfold higher bacterial colony count in blood drawn through the catheter c o m p a r e d to simultaneously drawn peripheral blood, a sensitivity of 94 %, specificity o f 100 % and positive predictive value of 100 % were obtained. Using a cut-off value of > 100 cfu/ml, the sensitivity and specificity of an isolated quantitative catheter blood culture were 82 % and 100 %, respectively.
Discussion Results A total of 107 vascular catheters from 64 patients with 67 febrile episodes were used for the study. These included 92 central venous catheters (36 subclavian, 16 internal jugular, 28 basilic, 10 femoral, 2 axillary) and 15 catheters placed in the
This study d e m o n s t r a t e s that differential quantitative blood culture is a useful technique for diagnosing catheter-related sepsis. Using this technique it is possible to diagnose or exclude catheter sepsis without catheter r e m o v a l when catheter-related sepsis is suspected clinically. A fourfold or greater difference in bacterial colony
Vo1.11,1992
405
Table 1: Comparison of results of paired quantitative cultures of peripheral venous blood and catheter blood, and semiquantitative culture of catheter tips in 17 patients with catheter-related sepsis and 22 cathetel~ inserted. O r g a n i s m count (efu/ml) Case no,
5 6 7 8 9 10 11 12 13 14 t5 16 17
Organism Peripheral blood
Staphylococcus epidermidis Staphylococcus epidermidis* Staphylococcus epidermidis* Staphylococcus epidermidis Staphylococcus epidermidis* Staphylococcus epidermidis Staphylococcus epidermidis* Staphylococcus epidermidis Staphylococcus epidermidis* Pseudomonas aerughzosa Staphylococcus epidermidis Staphy'lococcus epidermidis Torulopsisglabrata Staphylococcus epidermidk Staphylococcus epidermidis Staphylococcus epidermidis Staphylococcus epidermidis Staphylococcus epidermidis Staphylococcus epidermidis Staphylococcus aureus Pseudomonas aeruginosa Staphylococcus epidermidis
45 45 45 5 5 40 40 1000 0 > 1000 > 1000 1000 > 1000 500 > 1000 13 > 10130
1
> 10ft)
26 90 5 8
18 500 20 > 1000
C a t h e t e r tip > 1000 0 0 > 1000 0 13 0 > 40 0 > 1000 > 1000 + broth > 1000 15 11 + broth > 1000 > 100 > 100 > 100 > 15 9
*No source of sepsis. Table 2: Comparison of results of paired quantitative cultures of peripheral venous blood and catheter blood, and semiquantitative culture of catheter tips in 13 patients with colonized and/or infected catheters (no, 1-13), and in 7 patients with sepsis unrelated to intravenous catheters (no. 14-20). Organism count (cfu/ml) Case no.
1 2 3 4 5 6 7 8 9 10
11 12 13 14 15" 16" 17 18 19* 20
Organism Peripheral blood
C a t h e t e r blood
C a t h e t e r tip
Staphflococcus epidermidb Staphylococcusepidermidb Staphylococcusepidermidis Staphylococcusepidermidis Staphylococcusepidermidis Staphylococcusepidermidb Staphylococcusepidermidis Staphylococcusepidermidis Klebsiellapneumoniae Streptococcusfaecal& Staphylococcusepidermidis Staphylococcusepidermidis Staphylococcusepidermidis
0 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 8 50 0 0 0 20 500 1 0 0
>50 > I00 > 100 > 100 > 100 16 10 > 1000 + broth + broth 45 > 100 4
Pseudomonasaeruginosa Staphylococcusepidermidis Staphylococcus epidermidis Enterobactercloacae Enterobacter cloacae Staphylococcusepidermidis Pseudomonasaeruginosa Staphylococcus epidermidis Staphylococcus epidermidb Candidaalbkans
