Staphylococcus aureus bacteremia caused by infected intravenous catheters

American

Journal

Volume

15

of Infectim Number

1

Control

February

1987

Joseph M. Mylotte, M.D. Carolyn McDermott, R.N. Buffalo, New York

A prospective study of all cases of Staphylococcus aureus bacteremia (SAB) has been ongoing at our institution since April 1983. Data collected as of December 1984 reveal that of 79 episodes of SAB identified, 28 (35%) were caused by infected intravenous catheters; 14 of these were peripheral catheters and 14 were subclavian catheters. Endocarditis or metastatic infection was not recognized; two patients, one with a prosthetic heart valve and the other with recurrent SAB, did not meet the criteria for these complications but the clinical circumstances were strongly suggestive. Six of the 28 patients (21%) died of their infection, and local complications (inflammation or purulent drainage at the insertion site) were common. Only four of 22 patients who recovered were administered antibiotics for >14 days. We conclude that patients with SAB caused by an infected intravenous catheter have a low risk of endocarditis or metastatic infection when the infected catheter is promptly removed and no risk factors (valvular heart disease or a prosthetic valve) are present that favor development of endocarditis. The duration of antimicrobial therapy need not exceed 2 weeks in this situation. The mortality related to SAB, however, was high and emphasizes the need to develop methods to prevent this infection. (AM J INFECT CONTROL 1987; 15: l-6)

Staphylococcus aweus is one of the most common organisms producing intravascular catheter infection in hospitalized patients.’ Several studies have noted that when the infected cathFrom the Department eases, State University Administration Medical Supported Reprint (lllF), 14215.

of Medicine, of New York Center.

by the Veterans

Division at Buffalo,

of Infectious Disand the Veterans

Administration.

requests: Joseph M. Mylotte, VA Medical Center, 3495

M.D., Infectious Diseases Bailey Ave., Buffalo, NY

eter is promptly removed ‘and antimicrobial therapy prescribed, the risk of endocarditis or metastatic infection is minimal.*-’ Evidence from these studies indicates that the duration of therapy need not be prolonged beyond 3 weeks in most cases and that this form of staphylococcal infection has a good prognosis. In contrast, Watanakunakorn and Baird6 retrospectively found a high risk of endocarditis in patients with catheter-associated S. aureus bacteremia (SAB). Recently, in another retrospective study, Libman and Arbeit3 found that 1

Armmcan

2 Mylotte and McDermott catheter-associated SAB was associated with a high frequency of complications, including shock, local suppuration, and metastatic infection, but the risk of endocarditis was minimal. We have monitored prospectively all episodes of SAB at our hospital since April 1983. On review of the data collected up to December 1984, we found that intravascular catheter infection was the single most common cause of SAB. Although the frequency of endocarditis or metastatic foci resulting from this infection was low, as we previously reported,’ the mortality was higher than in the earlier period. These findings prompted this report, which emphasizes the considerable mortality related to this infection despite the apparent low risk of endocarditis.

The Buffalo Veterans Administration Medical Center is a tertiary care, university-affiliated hospital with 700 beds. There is no intravenous therapy team, and peripheral intravenous catheters are inserted by physicians or nurses; central venous catheters are inserted only by physicians. Guidelines have been established by the hospital Infection Control Committee for the proper insertion and care of both peripheral and central venous catheters. However, it is each practitioner’s responsibility to adhere to these guidelines. At present the frequency of deviation from these guidelines cannot be determined. During the study period the duration of time a catheter was in place usually could not be accurately determined from patient records, especially for peripheral venous catheters. The methods for case identification and the criteria used to define S. attrez4.s in blood cultures as representing a true bacteremia as well as the criteria for determining the presence of endocarditis, secondary foci of infection, and mortality caused by infection have been published.5 Follow-up of patients who were discharged was done by retrieving hospital records and noting findings on their last hospital visit. Patients who recovered from the SAB but remained hospitalized were seen weekly and evaluated for evidence of metastatic or recurrent S. aureus infection. During the period from April 1983 to December 1984,79 episodes of SAB were identified. Of

INFECTION

Joumai

of

CONTROL

these 79 episodes, 28 (35%) were determined to be caused by intravascular catheter infections on the basis of the following criteria developed before beginning the study. A peripheral intravenous catheter was considered to be the source of SAB if no other focus of infection was identified and one or more of the following was present: inflammation at the site of insertion of the intravenous catheter, purulent drainage from the insertion site that on culture grew S. uureus with or without inflammation, or a positive semiquantitative culture of the catheter for S. aureus as described by Maki et al.’ A central venous catheter (all subclavian vein catheters in this study) was considered to be the source of the SAB if no other focus of infection was found and one or both of the following applied: a semiquantitative culture of the catheter was positive for S. aureus, or there was purulent drainage from the insertion site of the catheter that on culture grew S. aureus. No episodes of SAB caused by infected arterial lines were dctected. One patient with SAB resulting from an infected Hickman catheter was identified but is not included in this report. Peripheral venous catheters were removed on development of signsofinflammationorpurulentdrainageat the insertion site. Central venous catheters were removed if there was purulent drainage at the insertion site, if a patient had an unexplained persistent (>24 hours) fever, or on recognition of positive blood cultures for S. aureus. In vitro antimicrobial susceptibility testing of S. atlretls isolates was done by the KirbyBauer method.’ Statistical analysis was done by the Student’s t test and chi-square analysis with Yates’ correction. A p value SO.05 was considered significant.

Twenty-eight patients had 28 episodes of catheter-associated SAB. Fourteen episodes were caused by infection of peripheral intravenous catheters (one of these was a catheter in the femoral vein), and 14 were related to infected subclavian vein catheters. The subclavian catheters were used as follows: nine for fluid replacement, two for total pat-enter-al nutrition, two for temporary hemo&alysis (Sorensen catheter), and one Swan-Ganz cathe-

Volume 15 Number February 1987

1

Catheter-induced S. aureus

bacteremia

3

T8ble 1. Antibiotics prescribed and duration of treatment in 22 patients who recovered from catheterassociated S. aureus bacteremia Days of treatment Type of catheter infection

No. of 0plSOdW

Antibiotics

admMHwed

Mean

Range

Antibiotic

No.

Nafcillin Cefazolin Nafcillin Cefazolin Vancomycin

6 3 4 1 8

Peripheral

9

15.4

11-28

Subclavian

13

14.8

5-28

ter (American Edwards Laboratories, Irvine, Calif.). The frequency with which a specific criterion was applied to define a catheter as the source of SAB was as follows. For peripheral venous catheter infection, inflammation with (four cases)or without (nine cases) purulent drainage at the insertion site was the most common finding. Semiquantitative catheter culture was performed only one time in this group and was positive. On the other hand, a positive semiquantitative catheter culture was the most common criterion used to make a diagnosis of central venous catheter infection (11 of 14 episodes); all but two infections in this group were corroborated by results of semiquantitative culture of the catheter or purulent drainage from the insertion site. Clinical characteristics of the 28 patients were as follows. The mean age of patients with peripheral catheter infection (57 years; range 48 to 89 years) was similar to the age of those with subclavian catheter infection (69 years; range 59 to 90 years). Catheter-associated SAB occurred more commonly on the medical service compared with the surgical service (71% versus 21%), but this difference was not statistically significant by chi-square analysis. The mean number of days of hospitalization before the development of SAB was twice as long for patients with subclavian catheter infection (48 days; range 2 to 180 days) as for those with peripheral catheter infection (21 days; range 3 to 80 days),. but considerable overlap occurred between the two groups. Methicillin-resistant S. czureus was isolated in six of 14 (41%) subclavian catheter infections and in one of 14 (7%) peripheral catheter infections, but this differ-

ence was not statistically significant. All patients had one or more underlying disease states: chronic alcoholism in seven, coronary artery disease in six, hypertension in eight, malignancy in seven, diabetes mellitus in five, chronic lung disease in five, chronic renal failure in three, and cerebrovascular accident in three. Local complications of catheter infection were common. Inflammation at the insertion site occurred in 13 of 14 with peripheral catheter infection, and four patients had purulent drainage. However, no patient required surgical intervention. Purulent drainage occurred at the insertion site of four infected subclavian catheters before their removal. Data on the treatment regimens used in the 22 patients who recovered from SAB are given in Table 1. The mean duration of antimicrobial therapy was similar for the two groups. All patients received only one antibiotic as treatment for SAB. Four of the 22 patients were given treatment for ~14 days (21,23,28, and 28 days). The decision to administer treatment in these four patients for 3 to 4 weeks was made by the primary care physician in each instance. There was no outstanding characteristic of these patients such as persistent fever, serious underlying disease, or persistent bacteremia that influenced thedecision toprescribeantibiotic therapy for > 14 days. Six of the 28 patients (21%) died as a direct result of the catheter infection; four of these had peripheral catheter infection and two had subclavian catheter infection. Of these six patients who died, one patient died on the day blood cultures were positive and did not receive antimicrobial treatment, one patient received one

Amer.can

4

Mylotte

T&te

and McDermott

2. Literature

review of intravenous

lannini and CrossIeyz Watanakunakorn and Bairdb Shah and Watanakunakorn” Mirimanoff and Glase? Cooper and Platt” Mylotte et aL5* Libman and Arbe? Bryan et al ‘2 Finkelstein et al ” of therapy

catheter-associated

and mortality

S. aureus

Journai

Meen No. days treatment

NO.

Patlants who dii of infection

%

No.

%

22

152

0

21

28

8

38

3

22 16 13 14

NS NS NS 203

4 1 1 0

18 6 8

NS NS NS 1

7

20 35

185 NS

0 NS

1 9

5 26

26

NS

0

NS

for the 14 patlents

were

not in orlgtnal

dose of an antibiotic and died shortly therafter, and four patients were given treatment for 3,5, 7, and 11 days, respectively, before their death. Four of the six patients who died had infections caused by methicillin-resistant S. atcreus. Eleven patients recovered from their infection but died of other causes during the same hospitalization, indicating the severity of the illnesses of patients who developed catheter-associated SAB. Duration of follow-up in these 11 patients ranged from 0 to 8 weeks (mean, 2.4 weeks). No evidence of metastatic infection or endocarditis was found during the follow-up period. The remaining 11 patients were discharged from the hospital. Seven of these 11 were alive with no evidence of recurrent staphylococcal infection after a follow-up period of 1.5 to 15 months, on the basis of review of their records. No follow-up information was available in the records of four patients. No cases of endocarditis were recognized clinically. In two cases, however, there was a possibility that endocarditis was present. One patient had an aortic valve prosthesis and died in severe left ventricular failure after 14 days of antibiotic treatment. At the time of death this patient had no clinical evidence of active S. aureus infection. Because no autopsy was performed, endocarditis cannot be excluded in this patient. A second patient signed out against medical advice after 11 days of treatment. He was readmitted 8 days later, and admission blood cultures were positive for S. aureus. Three days later the patient died of Escherichia co2i

pubkatlon

oi

CONTROL.

bacteremia Patients with andocardttis

Patients with cathaterassociated bacteramia (NO.)

Rafarence

NS = not stated *Data on duration

INFECTION

and are now given

0

speckally

14

for this group

bacteremia; no autopsy was performed. Endocarditis or a metastatic focusufinfection cannot be excluded in this patient. In none-of the patients did a clinically apparent secondary focus of infection develop. Only one autopsy was performed among the 17 patients who died and in this case no evidence of endocarditis was fol;tnd.

Table 2 lists the recent literature that provides information about intravenous caheterassociated SAB occurring in the setting of a general hospital. Studies dealing orrly with,specific patient populations such as cancer p&e&s or patients receiving hemodialysis were not included. Only two studies have specifically dealt with this infection,2, ’ and both were retrospective and found a remarkably different risk of endocarditis. Iannini and CrussIey2 reviewed all cases of SAB during a 4-year period at their institution and identified 29patients with SAB caused by a removable focus of infection. Twenty-two of these cases were related to an intravascular catheter infection. In none of these patients did endocarditis develap.after removal of the device and a mean duration-of antibiotic therapy of approxim&tely 2,astecks. In contrast, Watan&makorn and $&Gr&’ &au-~d a 38% frequency of endocarditis in a group of 2 1 patients with intravenous catheter-associated SAB. However, caution is necessary in the interpretation of this Latter report. This steady covered a period of approximately 9 years-4 2.967 to’ 1976) and included only patients seen in con-

Volume February

15 Number

1

1987

sultation by an Infectious Diseases Service. Therefore, the authors may not have included in their review all cases of catheter-associated SAB during the study period, as was done by Iannini and Crossley. It is possible that other patients with catheter-associated SAB were not seen in consultation either because the source of infection was not recognized or because the patients did well and did not require consultation. The patients seen in consultation may have represented those who were more seriously ill or had more complicated courses. Such a subgroup of patients would have a tendency to have a higher rate of complications. In a study of all cases of SAB at the same institution from 1975 to 1977 Shah and Watanakunakorn9 found that the rate of endocarditis related to 22 cases of catheter-associated SAB was 18%. That 22 cases of catheter-associated SAB were identified between 1975 and 1977 and only 21 cases were reported for the period 1967 to 1976 also suggests that not all cases of catheter-associated SAB were identified in the earlier study. Since these earlier reports, there have been several studies dealing with SAB in which can be found some information about the risk of endocarditis and mortality in patients with catheter-associated SAB (Table 2). These studies have, for the most part, found a minimal risk of endocarditis and a good prognosis. In the present report, 28 patients with intravenous catheter-associated SAB were prospectively evaluated for complications of the infection, specifically endocarditis and metastatic infection. We found little evidence of either in our patients. This is probably related to prompt recognition of the infection, removal of the catheter, and administration of antibiotic therapy. However, local complications such as inflammation and suppuration were common. Two patients, one with a prosthetic heart valve and another with recurrent S. auretls bacteremia, may have had endocarditis or metastatic infection. Both patients died, but no autopsies were performed. Because of the clinical circumstances in these cases, both would have been highly suspect cases for endocarditis or metastatic infection and would have received prolonged (4 to 6 weeks) antimicrobial therapy. It is possible that some patients in the present study had endocarditis or metastatic infection

Catheter-induced

S. aureus bacteremia

5

that was not recognized but was successfully treated with 2 weeks of antimicrobial therapy. This is unlikely, however, because a high failure rate would be expected in patients with S. uureus endocarditis given treatment for <4 weeks.‘O In those patients who recovered from the SAB, follow-up did not uncover evidence of recurrent S. aUYez4sinfection or metastatic foci. Also, excluding the two patients previously mentioned, the remaining 26 patients had no evidence of valvular heart disease or prosthetic heart valves, twa factors known to be the main predisposing factors for the development of nosocomial endocarditis.” This is important because a shortcoming of our study was the lack of autopsies (only one in the 17 patients who died) to verify the absence of endocarditis or metastatic infection. Eighteen of the 22 patients who recovered from SAB in our study received 14 days or less of antibiotic therapy without any clinical evidence of endocarditis or metastatic infection on follow-up. These findings are in agreement with most of the previously published retrospective studies listed in Table 2. In the absence of risk factors for nosocomial endocarditis” our findings support the approach of administering 2 weeks of antimicrobial therapy in patients with intravenous catheter-induced SAB after catheter removal. Because other studies3, 4 have identified metastatic infections in patients with catheter-associated SAB, antimicrobial therapy should be administered parenterally and the patients observed closely in the hospital. It should be emphasized that despite the low risk of endocarditis in our patients with catheter-associated SAB, the mortality rate was high (21%) compared with that found by previous studies. Bryan et al.‘* also recently reported a high mortality rate (26%) in patients with catheter-associated SAB in a retrospective study of SAB occurring at four hospitals. The high mortality rate is not unexpected because most of our patients were elderly and all had significant underlying diseases. These characteristics have previously been found to be poor prognostic factors in patients with SAB’O and S. aUrez4s endocarditis.’ It is unlikely that any major reduction will occur in the mortality rate of catheter-associated SAB, even with appropriate antimicrobial

American

6

Mylotte

and McDermott

INFECTION

treatment, especially in an elderly patient population such as ours. Bryan et al.‘* found that early initiation of appropriate antibiotic therapy had no impact on outcome in patients with SAB. Most patients dying of SAB, regardless of the source of bacteremia, do so within the first 2 weeks of treatment. ‘) 9 In our opinion, a major impact may be made on the mortality and morbidity of this problem only by using preventive measures. Guidelines for prevention of complications of intravenous catheterization have ben published.13 Among other things, these guidelines suggest that an intravenous therapy team may be useful, although no proof was offered to support this. Recently, Tomford et a1.14 have provided prospective controlled data indicating that such a team can substantially reduce the complications related to peripheral intravenous catheters. Although the actual incidence of intravenous catheter-associated sepsis in our institution is not known, we were alarmed by what we perceived to be an excessive number of such infections over a relatively short period. The findings reported in this study have led, in part, to ongoing discussions concerning the establishment of an intravenous therapy team at our medical center. In summary, during a 21-month period 28 of 79 (35%) episodes of SAB were caused by infected intravenous catheters, the single most common cause of SAB during the study period. The 21% mortality rate caused by catheter-associated SAB in this study was higher than in most previous reports. The risk of endocarditis or metastatic infection, however, was minimal and on the basis of these findings we continue to recommend a 2-week course of parenteral antibiotic therapy in most cases of catheter-associated SAB along with catheter removal. We thank Ms. Sally Maier script.

for preparation

of the manu-

1. Maki DC: The prevention and management of devicerelated infection in infusion therapy. J Med 11:239-253, 1980.

Journal

of

CONTROI.

2. Iannini W, Crossley KB: Therapy of Staphylococcus aureus bacteremia associated with a removable focus of infection. Ann Intern Med 84:558-560, 1976. 3. Libman H, Arbeit RD: Complications associated with Stuphylococcus aureus bacteremia. Arch Intern Med 144:541-545,

1984.

4. Mirimanoff RO, Glaser MP: Endocarditis during Staph~ZOCOCCUS aureuS septicemia in a population of non-drug addicts. Arch Intern Med 142:1311-1313, 1982. 5. Mylotte JM, Beam TR, Alien JC: Staphylococcus uweus bacteremia: A prospective study. South Med J 76: 113 l1135, 1983. 6. Watanakunakorn C, Baird IM: Staphylococcus aweus bacteremia and endocarditis associated with a removable infected intravenous device. Am J Med 63:253-256, 1977. 7. Maki DC, Weise CE, Sarafin HW: A semiquantitative culture method for identifying intravenous catheterrelated infection. N Engl J Med 246:1305-1309, 1977. 8. Bauer AW, Kirby WMM, Sherris JC: Antibiotic susceptibility testing by a standardized single disk method. Am J Clin Path01 45:493-496, 1966. 9. Shah M, Watanakunakorn C: Changing patterns of Staphylococcus aureus bacteremia. Am 3 Med Sci 278:115-121, 1979. 10. Nolan CM, Beaty HN: Staphylococcus cureus bacteremia. Current clinical patterns. Am J Med 60:495-500, 1976. 11. Friedland G, vonReyn CF, Levy B, Arbeit R, Dasse P, Crumpacker C: Nosocomial endocarditis. Infect Control 5:284-288, 1984. 12. Bryan CS, Kirkhart B, Brenner ER: Staphylococcal bacteremia: Current patterns in nonuniversity hospitals. South Med J 77:693-&i, 1984. 13. Simmons BP, Hootan TM, Wong EG, et al: Guidelines for prevention of intravascular infections. Infect Control 3:61-67, 1982. 14. Tomford JW, Hershey CO, McLaron CE, Porter DK, Cohen DI: Intravenous therapy team and peripheral venous catheter-associated complications-a prospective controlled study. Arch Intern Med 14&f 191-1194, 1984. 15. Cooper G, Platt R: St&yZococcus uweus bacteremia in diabetic patients-endocarditis and mortality. Am J Med 73:658-662, 1982. 16. Finklestein R, Sobel JD, Nagler A, Merzbach D: Stuphylococcus aureus bacteremia and endocarditis: Co& parison of nosocomial and community acquired infection. J Med 19:193-211, 1984.