Long-term follow-up of patients with catheter-related bacteremia treated without catheter removal

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Clinical M i c r o b i o l o g y a n d Infection, Volume 4 N u m b e r 8 , A u g u s t 1998

a blood volunie less than 3 mL, and 2893 (40.1%) bottles received a blood volume larger than 10 mL. It is striking that only 14.3% of the bottles met the optimal volume criterion and that roughly half of the bottles were inadequately filled. In a siniilar audit that we performed earlier [3], we found the 4.5% false-positive rate to be clearly associated with overfilling, and this phenomenon has also been reported for analogous blood culture systems [2]. In the present study, we found false positives in 57 (2.0%) of 2839 overfilled bottles but no false positives in the 1028 bottles containing the optimal blood volume. Apparently, the revised software in the BACTEC 9240 analyzer (version 3.61F in the present study) compensates for false-positive readings due to overfilling. O f more concern is the number of underfilled bottles. The direct-draw technique does not allow the user to control the volume of blood by comparing the blood-broth column height with the volume indications on the product label. When queried about this finding, the phlebotomists in our hospital pointed to the lack of a well-defined ‘endpoint’ that could indicate when to withdraw the bottle from the needle-holder. Nearly one third of the phlebotomists stated that they did not withdraw the bottle until complete depletion of the vacuum, a procedure that may result in overfilling. In the case of a difficult venipuncture, however, they tend to withdraw the bottles rather fast to ensure filling of the remaining bottle and eventual other blood-collecting tubes, an action that may result in underfilling. Underfilling may have been due to the instructions as stated 011 the label: ‘range 3-10 niL‘ and ‘optimal 8-10 i d ’ . This asymmetry is confusing, as it suggests that the lower volume limit is less crucial than the upper one. Furthermore, there was much confusion concerning the volume range, with only 25 (16.9%) of the interviewed phlebotomists being aware of the correct optimal volume. In recent years, the layout of the product label on the BACTEC”LU4/F bottles has been changed several times, with an extension of the reconimended blood volume. We argue that the label should clearly state that the optimal volume of blood is 8-1 0 niL/bottle and that 3 mL and 1 0 mL are the limits of acceptable blood volumes for each bottle. Further, phlebotomists should be notified of the appropriate blood volumes for culture. Repeatedly, we demonstrated a poor compliance rate in filling BACTECP‘“’/F bottles. The direct-draw blood sampling technique of these bottles has to be evaluated and a filling endpoint has to be defined, in order to give appropriate directives to achieve compliance with the reconimended blood volume to be added to the blood culture bottle. The present study

indicates that volumes of blood for culture should be monitored routinely as a quality assurance measure.

Kico E . L. Meexscri arid Jan A . Jacobs Department of Medical Microbiology, University Hospital Maastricht, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands Fax: +31 433876643

Accepted 31 March 1998

References Li J, Plorde JJ, Carlson LG. Effects ofvolume and periodicit)on blood cultures. J Clin Microbiol 1994; 32: 2829-31. Alfa M, Sanche S, Ronian S, Fiola Y, Lentoii P, Hardirig G. Continuous quality improvement for introduction of autoniated blood culture instrument. J Clin Microbiol 1995; 33: 1185-91. Meessen NEL, Jacobs JA. Blood volume in UACTEC PLUS culture vial$. Clin Microbiol Infect 1997; 3(wppl 2): 265.

Long-term follow-up of patients with catheter-related bacteremia treated without catheter removal

Clin Mirvohiol Infect 1998; 4: 472-476 It has been demonstrated that central venous catheterrelated bactereinia (CRB) can be treated without catheter renioval under certain clinical circumstances by the use of local intracatheter antibiotics (antibioticlock technique) plus systemic antibiotics 11-81, This conservative approach permits preservation of the vascular access in patients who require it for long periods of time, such as those receiving oncologic treatment, home parented nutrition or periodic hemodialysis sessions 19-1 11. The advantages of maintaining the catheter are well established in terms of cost and patient comfort. There dre questions, however, concerning the possible development of long-term septic complications, such as endocarditis or spondylitis [12-141, derived from maintaining an infected device until microbial eradication has been completed. Moreover. there are no reports that conclusively describe the functionality and duration of- sustained catheters. The aini of this study was to analyze the outcoine of a cohort of patients who had experienced an episode of CXB and were treated without catheter removal, in order to evaluate the patency and usefulnesc of sustained catheters and the emergence of late infectious complications. During a 41-month period (October 1990 to February 1994), we prospectively followed up all patients with a central venous catheter (Pernicath)

Concise Communications

implanted for hemodialysis purposes in the nephrology unit of an 850-bed university hospital. All cases were in the end stage of chronic renal disease and needed periodic hemodialysis treatment. The Permcath Quinton (A.H. Robbins Co., USA) is a 28-cm, radiopaque, double-lumen silicone rubber catheter with a Dacron felt cuff. AU catheters were inserted into the internal jugular vein and were used only for hemodialysis. Catheters were implanted and removed under sterile conditions in the operating room. CRB was suspected when a patient in whom a Permcath catheter had been inserted developed unexplained fever (temperature >37.5"C) and/or clinical signs of infection in the absence of other documented infections. Diagnosis of CRB was established on the basis of microbiological criteria, i.e. quantitative culture of blood samples (Schottmuller technique) simultaneously obtained from a peripheral vein and through each catheter lumen. Bacteremia was considered to be catheter-related when (1) the same microorganism was isolated from one or more peripheral blood cultures and one or two quantitative blood cultures obtained through the catheter, (2) there was a fourfold increase or more in bacteria colony counts (CFU/mL) between the quantitative blood cultures obtained via the catheter and via the peripheral vein, and (3) no primary infective site other than the catheter could be identified clinically or bacteriologically. Bacteremia was classified as unrelated to the central venous catheter when bacterial counts obtained via the catheter were not fourfold higher than identical bacterial colonies in the peripheral blood specimen. The accuracy of this cut-off limit for positivity was assessed in a previous study by our group [IS]. CRB treatment consisted of simultaneous antibiotic administration locally intracatheter (antibioticlock technique), and intravenously, as has been previously described [ 111. After blood cultures were drawn from the catheter and from a peripheral vein, patients who appeared to have CRB were empirically given ciprofloxacin as initial antimicrobial therapy. Thereafter and according to bacteriologic results, antibiotic was discontinued or modified. The antibiotics administered were vancomycin (1 g/week) or ciprofloxacin (200 mg) at the end of each hemodialysis session, depending on the bacterial isolates. Antibiotics were given by 4-h continuous infusion via the hemodialysis catheter (half of the dose through each lumen). In addition, using the antibiotic-lock technique, 2 mL of a solution of vancomycin or ciprofloxacin, 100 mg/L in 5% sodium heparin, was injected into each catheter lumen between two hemodialysis sessions. Antibiotic administration lasted for 15 days. The exclusion criteria for conservative manage-

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ment of a CRB episode were: phlebitis and/or purulent exudate, presence of foreign bodies such as prosthetic heart valves, vascular grafts, pacemakers or/and orthopedic prostheses, sepsis with clinical complications, such as septic shock, disseminated mtravascular coagulation and/or respiratory insufficiency, pulmonary embolism, infective endocarditis, and positive blood cultures for yeast. It was also intended that patients with persistent bacteremia 48-72 h after starting therapy should be excluded from conservative treatment; thus, quantitative blood cultures were performed at 48-72 h, and after finalizing treatment. Beginning from the time that .in episode of CRB had been diagnosed and treated, the patients were prospectively followed up. Every time that a patient had fever or complained of any clinical sign suggestive of infection, a complete evaluation was done. The study protocol consisted of a careful physical examination, including insertion site and tunnelization, hemogram and biochemistry analysis, peripheral and catheter quantitative blood cultures, urine culture when feasible, culture of all secretions, and other complementary explorations (e.g. echocardiography, computed tomography scan) depending on clinical manifestations. When a patient no longer required the catheter, because an arteriovenous fistula had developed or the function of a transplanted kidney had become effective, the catheter was aseptically rem0vt.d in the operating room. The extracted catheters were cultured by the semiquantitative method proposed by Maki et a1 [16]. The patients studied were followed up whether their catheters remained in place or not. The follow-up period was completed in May 1994.. Over the study period, implanted jugular catheters were applied for hemodialysis in 185 patients. O f these, 37 patients (23 males; mean age 54.5 years, range 22-81) experienced a total of 42 episodes of CRB. This figure represents 0.13 episodes of C R B per 100 days of indwelling catheter use. The microorganisms responsible were: Staphylococcus epidermidis (20 episodes), Staphylococcus aureus (13), Pseudoinonas aeruginosa (€9, Enterococcus faecalis (l), Corynebactcriurn jeikenum (l), Stauotrophomonas maltophila (l), and Klebsiella pneumoniae (1). Two patients presented exclusion criteria for conservative management of CEU3: one had a knee prosthesis (Staphylococcus aureus CRB) and other presented initial hypotension (I? aeruginosa CRB). All cases managed with the catheter in place were afebrile after 24-48 h of treatment, with negative quantitative blood cultures. At the end of the study (May 1994), 10 patients had died (four acute myocardial infarction, two neurologic stroke, one mesenteric ischemia, one multiple

C l i n i c a l M i c r o b i o l o g y a n d I n f e c t i o n , V o l u m e 4 N u m b e r 8, A u g u s t 1 9 9 8

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Table 1 Patients with more than one episode of catheter-related sepsis Etiologyh

Interval (days)

J? nrru$ittosa J? aWUglllCJSd Staphylococcus aiirriis S . epiderniidis S . epiderniidis Staphylococrtis aiireiu

85 65

Etiologya

P nerngimsa I?aeni'Tinosa S. tyiderniidir Staplrylococcirr aiireii3 Staphylocorcirj aweus

360 520 335

Echocardiography Normal Normal Nortnal Myocardiopathy Nornial

Outcome Transplant Heart failurc Death A-V fistula A-V fistula A-V fistula

.'First episode, hSccond episodc. A-V. arteriovenous.

myeloma, one upper gastrointestinal bleeding, and one peritonitis), five had received a successful kidney transplant and 20 remained on intermittent hemodialysis by arteriovenous fistula. The mean duration of the follow-up period for each patient was 20.5 months (range 2-44 months). After the initial episode of CRB, the median duration of the time for which the catheter remained in place was 90 days (range 16-670 days). Five patients presented a second episode of CKB after a mean infection-free interval of 5.3 months (range 1-8 months). In Table 1, we show the etiology of the two episodes, the interval of time between them, echocardiography results and the final outcome of follow-up in these patients. These second episodes of C R B were considered to be new and not relapses, because of the extended length of the infectionfree period and the different microorganisms isolated

~71. None of the patients developed infectious complications or distant septic metastasis that could be associated with the episode of CRB. An echocardiographic study was performed a t least once in 18 patients. The five patients who received a kidney transplant suffered eight episodes of infection unrelated to the catheter: five were infections of the urinary tract caused by Esclierichia ruli and/or K . pneurnouiae, and three were episodes of cytoinegalovirus disease. None of the catheters treated conservatively had to be removed because of infection. All maintained patency and usefulness until they were removed when hemodialysis became unnecessary; at that time all had a negative tip culture. The object of this report is not to emphasize the short-term efficacy of conservative C K B antibiotic treatment applied under certain clinical circuinstances that suggest it, as in patients who need long-term central venous access. At the present time, this conservative approach is well accepted in the literature [I-111. For the initial, empirical treatment, we chose ciprofloxacin because of its broad coverage against Gram-positive cocci and Gram-negative bacilli. When

a Gram-positive microorganism was identified, antibiotic treatment was shifted to vancomycin. Both antibiotics are stable at 37°C for more than 72 h, and at the concentrations used we have not observed precipitation with heparin. Two patients with Staphylococcus aureus CKB died from strokes. Although neurologic manifestations are frequent in Staphylococcus aureus endocarditis, neurologic involvement usually occurs in the acute phase of endocarditis, concomitantly with septic manifestations and cardiac valve destruction [18, 191. Echocardiograms were not performed in these two patients because they appeared well. Stroke developed suddenly without other clinical signs of infection and after a long interval from the CKB episode, 11 and 2 months respectively. We reasonably excluded infectious endocarditis in these patients, who frequently present with stroke, related to renal failure and hemodialysis. During the follow-up period, 18 echocardiograms were performed (nine Staplzylococcur aweus CKB, seven S. epidevmidis. one I? aevugiriosa and one Corynebacteriuni sp.), and no data suggestive of endocarditis were found. The absence of complications in our series, and the pernieability of the catheter for the duration of its application, strongly argues in favor of the conservative management of C R B in these patients. Five patients (14%) developed a second episode of C K B that we considered unrelated to the initial episode because of the long infection-free period between episodes [I 71. In three of these patients we could not unequivocally ensure that the second episodes were not actually relapses of infection because we did not perform an epideniiologic typing of the microorganisms isolated and the antibiotic susceptibility pattern did not permit a firm conclusion. Nevertheless, these second episodes also evolved favorably with a new course of conservative antibiotic therapy. Benerza et a1 [7] reported that 61% of C X B cases in cancer patients were successfully treated with antibiotics. In a large series of C R B caused by coagulase-negative staphylococci, Raad et a1 [20]

Concise Communications

observed no acute infectious complications in the treatment of bacteremia while maintaining the catheter in place. However, in this retrospective study, the authors found 20% of recurrences in the patients in whom the catheter was not changed. In both these studies [7,20] the antibiotic treatment for bacteremia consisted of only intermittent administration of the drugs; efforts were not made to sterilize the catheter locally, as in the antibiotic-lock technique. Treatment of Hickman catheter-related sepsis has been accomplished successfully using the antibioticlock technique [21]. Although repetitive episodes of C R B are frequent in patients with prolonged indwelling catheterization, antibiotic lock has shown to be useful and free from complications when patient selection criteria are appropriate, in both the short and long term. Marr et a1 [22] have described their experience on the advisability of maintaining the infected catheter in hemodialysis patients with CRB. They report that only 12 catheters in 62 episodes of bacteremia (19%) were salvaged. This strongly contrasts with the experience presented here, but there are many differences between the two studies. In contrast to the work of Marr et a1 [22], we confirmed all episodes of C F U with paired quantitative blood cultures, and all catheters removed during follow-up were microbiologically assessed to confirm catheter infection or cure. In our patients we used the antibiotic-lock technique to achieve high concentrations of antibiotics within the catheter during the interdialysis period. Patients on hemodialysis are given low doses of antibiotics because of renal failure. In this situation the catheter is briefly in contact with the frequently administered antibiotic only once a week. The fact that no attempts were made to sterilize the catheter could explain the low success rate in this study as compared to our results. Although this is a prospective cohort study without a comparison group, we believe that our results are useful for clinicians and investigators involved in the management of catheterized patients in hemodialysis units. Our follow-up included a large number of patients who were examined regularly by the same medical staff over a long period of time. Nevertheless, to define the safety of conservative management of CRB episodes in other clinical settings, with different patient populations and types of catheters, more experience is needed. Acknowledgments This paper was presented in part (abstract no. 53) at the 35th Interscience Conference on Antimicrobial Agents and Chemotherapy, in San Francisco, USA, in September 1995. This work was supported in part

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by DGICYT grant PM93/1230. The authors thank Celine L. Cavallo for her editorial assistance. Josep A. CapdevilGI I * , Alfons Segarra’, A . M . Planes3, Isabel Gasser3, Joan Gavaldh I , Pilar Ruiz Valverde’ and Albert Pahicsa I Servei de Malalties Infeccioses, Hospital General ‘Valld’Hebrhn’, Passeig Vall d’Hebr6n 119-129, Barcelona 08035, Spain; Departments of 2Nephrology, ‘Microbiology, Hospital General Vall d’Hebr6n, Universitat Autbnoma, Barcelona, Spain *Tel: +34 3 2746057 Fax: t34 3 2746057 Accepted 26 March 1998

References 1. Weightman N C , Simpson EM, Speller DCE, Mott MG, Oakhill A. Bacteraemia related to indwelling central venous catheters: prevention, diagnosis and treatment. Eur J Clin Microbiol Infect Dis 1988; 7: 125-9. 2. Lewis JA, LaFrance R, Bower RH. Trratment of an infected silicone right atrial catheter with combined fibrinolytic and antibiotic therapy: case report and review of the literature. J Parenter Enteral Nutr 1989; 13: 92-8. 3. Nahara MC, King DR, Powell DA, hlarx SM, Ginn-Pease ME. Management of catheter-related infections in pediatric patients. J Parenter Enteral Nutr 1988. 12: 58-9. 4. Messing B, Peitra-Cohen S, Debure A, Beliah M, Bernier J. Antibiotic-lock technique: a new approach to optimal therapy for atheter-related sepsis in home parenteral nutrition patients. J Parenter Enteral Nutr 1988: 12: 185-9. 5. Prince A, Heller B, Levy J, Heird WC. Management of fever in patients with central vein catheters. Pediatr Infect Dis 1986; 5: 20-4. 6. Capdevila JA. DiagnBstico y tratamiento de la sepsis por catt-ter. M r d Clin (Barc) 1991; 97: 506-10. 7. Benerza D, Khien TE, Gold JWM, 13rown AE, Turnbull ADM, Armstrong D. Prospective study of infections in indwelling central venous catheters using quantitative blood cultures. Am J Med 1988; 85: 495-8. 8. Benoit J-1, Carandang G, Sitrin M , Arnow PM. Intraluminal antibiotic treatment of central venous catheter infections in patients receiving parenteral nutrition at home. Clin Infect Dls 1995; 21: 1286-8. 9. Abrahm JL, Mullen JL. A prospective study of prolonged central venous access in leukemia. J h l A 1982; 248: 286873. 10. Simon C, Suttorp M. Results of antibiotic treatment of Hickman-catheter-related infections in oncological patients. Support Care Cancer 1994, 2: 66-70. 11. Capdevila JA, Segarra A, Planes AM, rt al. Successful treatment of haemodialysis catheter-related sepsis without catheter removal. Nephrol Dial Transplant 1993; 8: 231-4.

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12. Ehnl WP, Keller B. Short-course therapy for catheterbactereniia. Arch Intern Med associated Staphylocorcirs ilrrre~~s 1989; 149: ,531-6. 13. Power J, Wing EJ, Tdldiiio TS, Stanko K. Fatal bacterial endocarditis as a conipliczition of permanent indwelling cdtheters. Am J Med 1986; 81: 166-8. 14. Tsao MMI’, Katz 1). Central venous catheter-induced endocarditis: human correlate o f the animal experimental model of endocarditis. K e v Infcct Uis 1984; 6: 783-90. 15. Capdei-ild JA, Planes AM, Paloniar M , et al. Usefulness of quantitmve blood cultlire for diagnosis of catheter related repsis. Eur J Cliri Microbiol 1992; 11: 403-7 16. Maki I X , Weire C E , Serafin HW. A seiiiiquantitative culture method for identifying intravenous-catheter-related infection. N Eiigl J Med 1977; 296: 1305-9. 17. Capdevila JA, Almirante B, Pahissa A, Platies AM, Kibei-a E, Martinez VXzquez JM. Incidence arid ritk facton of recurrent episodes of bactereniia in adults. Arch Intern Med 1994: 1.54: 41 1-15. 18. Koder 13L, Wandall IIA, Ehperse F, Friniodt-MoUer N , Skinhoj l’, Kosdahl VT. Neurologic manifestations i n

Stny~lrylococc~rs tirireiis endocarditis: a review of 260 bacterieinic cases in nondrug addicts. Am J M e d 1997: 102: 379-86. 19. Almirante B, Tornot MP, Mirahet S, Pigrau C:. Soler J. Pahissa A. Stuphylncvcru oiircirs infectious endocarditis (IE): deleterious effcct o f anticoagulants? [abstract K-431. In: Abhtrxts of the 37th Iiiterscience Conferencc on Antiniicrobial Agents and Cheniotherdpy, Toronto. Washirigton. DC: American Society for MicrobioIo&y, 1997: 33.5. 20. Kaad 1, L3avis S , Khan A, Tdrrand J, Elting L, Uodey GP Impact of central venous catheter removal on the recurrence of catheter-related coagulase-negative staphylococcal bactereniia. Infect Control Hosp Epideniiol 1991; 13: 21 5-

21. 21. Krzywda EA, Andri\ DA, Edniicton ChE, Quebbemxi E. Treatment of Hicknian catheter sepsis using antibiotic lock technique. Infect Control Hosp Epideniiol 1995; 16: 59(,-8. 22. Marr KA, Sextori UJ, C:onloii PJ, Corey GK, Schwab SJ, Kirkland KB. Catheter-related bactereniia and oiitcoiiie of xtenipted catheter salvage in patients uiidergoing hemodialysis. Ann Intern Med 1997; 127: 275-80.