Cardiovasc Intervent Radiol t l%gl) 13:102-106
CardioVascular andInterventional Radiology 9 Springer-Verlag New York Inc. 1990
Antibiotic Bonded Nephrostomy Catheters for Percutaneous Nephrostomies John L. N o s h e r , J A l a n S. E r i c k s e n , ~ S t a n l e y Z. T r o o s k i n , 2 G a r y S. N e e d e l l , j R i c h a r d A. H a r v e y ) and R a l p h S. G r e c o : Departments of ~Radiology, :Surgery. and 3Biochemistry, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey. USA
A b s t r a c t . A p r o s p e c t i v e c o n t r o l l e d trial o f the effectiveness of a cefoxitin-bonded nephrostomy catheter was u n d e r t a k e n to d e t e r m i n e the e f f e c t i v e n e s s o f an a n t i b i o t i c b o n d e d c a t h e t e r in d e c r e a s i n g the infectious c o m p l i c a t i o n s o f p e r c u t a n e o u s n e p h r o s t o m y . The s t u d y c o n c l u d e s that b o n d i n g o f the antibiotic c e f o x i t i n to p e r c u t a n e o u s n e p h r o s t o m y cathe t e r s did not influence the i n c i d e n c e o f b a c t e r i u r i a o r u r i n a r y t r a c t infection. In additiQn, o b s e r v a t i o n s on the o v e r a l l i n c i d e n c e o f c o m p l i c a t i o n s from percutaneous nephrostomy are made.
Key words: A n t i b i o t i c b o n d e d c a t h e t e r - - P e r c u t a neous nephrostomy--Nephrostomy tion--lnfectious complication
complica-
bonded continuous ambulatory peritoneal dialysis (CAPD) catheters and vascular catheters have been s h o w n to be e f f e c t i v e in r e d u c i n g b a c t e r i a l c o l o n i z a tion a n d in i n c r e a s i n g r e s i s t a n c e to infection in animal m o d e l s [5-8]. P r e l i m i n a r y r e s u l t s o f a clinical trial h a v e d e m o n s t r a t e d d e c r e a s e d c a t h e t e r tract infection a n d p e r i t o n i t i s in p a t i e n t s r e c e i v i n g antibio t i c - b o n d e d C A P D c a t h e t e r s [9]. W i t h t h e s e r e s u l t s in mind, the c u r r e n t s t u d y was u n d e r t a k e n to i n v e s tigate the e f f i c a c y o f a p r o t o t y p e a n t i b i o t i c b o n d e d n e p h r o s t o m y c a t h e t e r in d i m i n i s h i n g the i n c i d e n c e . and d e l a y i n g the o n s e t o f b a c t e r i u r i a , s y m p t o m a t i c urinary tract infection, and catheter occlusion.
Materials and Methods In Vitro B o n d i n g o f A n t i b i o t i c to C a t h e t e r
P e r c u t a n e o u s n e p h r o s t o m y is a safe and effective m e t h o d for t r e a t m e n t o f o b s t r u c t i v e u r o p a t h y , for d i v e r s i o n o f urine f r o m the u r e t e r o r b l a d d e r , and for gaining a c c e s s to the u r i n a r y tract for i n t e r v e n tional p r o c e d u r e s . T h e p r o c e d u r e can be p e r f o r m e d s u c c e s s f u l l y in a l m o s t all p a t i e n t s , with few perip r o c e d u r a l c o m p l i c a t i o n s , but l o n g - t e r m c o m p l i c a tions including i n f e c t i o n , c a t h e t e r o c c l u s i o n , and d i s l o d g e m e n t a r e f r e q u e n t [1-3]. B j o r n s o n et al. [4] h a v e d e m o n s t r a t e d that bacterial m i g r a t i o n f r o m the skin a l o n g c a t h e t e r surfaces is m o r e significant in the i n f e c t i o n o f i n t r a v e nous catheters than is hematogenous c o n t a m i n a t i o n ; this o b s e r v a t i o n led to the d e v e l o p ment of antibiotic bonded catheters. Antibiotic-
Address reprint requests to: John L. Nosher, M.D., Department of Radiology. UMDNJ-Robert Wood Johnson Medical School, One Robert Wood Johnson Place - CN 19, New Brunswick, New Jersey 08903-0~)19, USA
Greco and Harvey [10] have previously described the binding of cefoxitin to polytetraflouroethytene coated with tridodecylmethyl-ammonium chloride tTDMAC). As part of the current study, the bonding and retention of antibiotic on polyethylene nephrostomy catheters was tested in uitro using ~4C-cefoxitin. One centimeter pieces of 10 French nephrostomy catheters were incubated with an aqueous solution of ~4C-cefoxitin (10 mg/cc) for 30 rain. The samples were washed five times in water and counted in a liquid scintillation counter to determine the retention of radiolabeled antibiotic. These samples were then incubated with vigorous stirring in human urine for 24 h in vitro and counted for radiolabeled antibiotic activity. Clinical Trial
Patients were eligible for this study if a percutancous nephrostomy catheter was clinically indicated for any reason and there was no history of hypersensitivity to the cephalosporin antibiotic cefoxitin, which was bonded to the experimental catheters. Twenty-two antibiotic bonded catheters (ABC) were placed in 17 patients and 26 nonbonded catheters (NBC) were placed in 18 patients. The average age of patients with ABC was 60 years (range 32-78) and of patients with NBC 59 years (range 8-80).
J.L. Nosher et al.: Antibiotic Bonded Nephrostomy Table 1. Underlying disease of patients and indication for nephrostomy
103 Table 2. Criteria for diagnosis of uJ-inary tract infection Bacteriuria of greater than 10.000 colony count (see text)
Indication
No. catheters (ABC, NBC)
Urinary obstruction (total) Due to malignancy Prostate CA Bladder CA Gynecologic CA Metastatic colon CA Metastatic breast CA Due to calculus Due to congenital anomaly Bladder hematoma Ureteral tuberculosis
43 (19,241 32 (15,17) 11 (6,5) 7 (3.4) 6 (3,3l 5 (1.4) 3 (2.1) 6 (3,3} 3 (I.2) I (0,1 ) 1 10, I )
UTI coexistent with obstruction due to any of the above
I1 (6,5/
Stone extraction (not obstructed)
3 (1 2}
Diversion for ureteral trauma
2 (2,0)
Total
48 (22,26)
Pyuria -> 10 white blood cells per high power field in unspun specimen Fever -> 100~ F in the absence of any other source of infection Abnormal white blood count (WBC) WBC ~ 10.000 with differential shift in the immunocompetent patient or Differential shift with or without WBC -> 10,000 in the immunocompromised patient, i.e., recent corticosteroid therapy or immunosuppressive chemotherapy
holding medium, and sent for culture, colony count, and organism identification. Stastical analysis of data included product survival analysis method for comparison of bacleriuria and UT1 in bonded versus control catheters. Fischer's exact test was used in the total population to evaluate the relationship of infection with other factors, including underlying disease.
ABC = Antibiotic bonded catheters; NBC = nonbonded catheters
Results Nine ABC and 10 NBC were placed in male patients and eight ABC and eight NBC were inserted in female patients. Indication for the nephrostomies and major cfitegories of underlying disease are listed in Table 1. Percutaneous nephrostomy was performed with the Seldinger technique utilizing ultrasound and fluoroscopic guidance. Catheters were randomly assigned to be either antibiotic bonded with cefoxitin (ABC) or to be nonbonded {NBC), serving as the experimental group and the control group. respectively. Several patients in the study were unable to give informed consent tbr the use of an ABC, and therefore, were assigned to an NBC which was outside the protocol sequence. Catheters used in the study were 8 or 10 French polyethylene pig-tailed or loop catheters. ABC catheters pretreated with the cationic surfactant 5% TDMAC in 95% ethanol were inserted into the patient. Urine was aspirated through the percutaneous access needle from the collecting system at the time of initial puncture and sent for culture. Routine culture was then performed on postinsertion days 1, 3, 7, 14 and thereafter, at 14-day intervals. Additional urine specimens were Obtained when the clinical status of the patient indicated the possibility of urinary tract infection. For the current study, a patient was designated as having bacteriuria if greater than 10,000 colony count was cultured from nephrostomy urine. Organisms from urine and catheter tips were identified, and correlated with the existence of possible clinical upper urinary tract infection (UTI). The criteria required for the diagnosis of clinical urinary tract infection are included in Table 2. Infrequently. a positive urine culture was not obtained from a patient with clinical upper UT[ which preceded nephrostomy who had received several days of systemic antibiotic therapy. In all other cases the patient with clinical UTI had culture-proven bacteriuria. A positive response of patients with clinical urinary tract infection to systemic antibiotic therapy was defined as resolution of the previously described criteria for clinical UTI. Complications of percutaneous nephrostomy other than urinary infection were also recorded. The protocol was completed when the nephrostomy catheter was removed for any reason. Upon removal of the catheter, the tip was inspected for any superficial or luminal debris termed "'encrustations" that may have accumulated. Under sterile conditions, each catheter tip was severed, placed in a microbial
In V i t r o Bonding o f Antibiotic to Catheter A f t e r s o a k i n g in r a d i o l a b e l e d L4C-cefoxitin s o l u t i o n a n d w a s h i n g in w a t e r , t h e s a m p l e s o f T D M A C treated catheters bound 24 beg c e f o x i t i n / c m , w h e r e a s u n t r e a t e d c a t h e t e r s r e t a i n e d l e s s t h a n 0.1 p , g / c m . F o l l o w i n g in vitro i n c u b a t i o n in h u m a n u r i n e f o r 24 h, T D M A C c a t h e t e r s r e t a i n e d 2 p,g o f cefoxitin/cm. This concentration of antibiotic has b e e n p r e v i o u s l y s h o w n in o u r l a b o r a t o r y t o b e b a c t e r i o c i d a l a g a i n s t Staph aureus in vitro.
Clinical Trial Forty-eight percutaneous nephrostomy catheters w e r e p l a c e d in 27 p a t i e n t s : 7 h a d b i l a t e r a l , s i m u l t a neous nephrostomies and 20 h a d s u c c e s s i v e nephrostomies or catheter replacements. The unit o f o b s e r v a t i o n f o r p u r p o s e s o f a n a l y s i s in t h i s s t u d y was each nephrostomy catheter. A separate analysis o f f i r s t c a t h e t e r s i n s e r t e d in e a c h r e n a l u n i t , w a s c o m p a r e d w i t h r e s u l t s f r o m all c a t h e t e r s t o e v a l u a t e the possibility of bias due to successive nephrostomy and catheter reinsertion. These results did not s i g n i f i c a n t l y d i f f e r f r o m r e s u l t s w h e n all c a t h e t e r s w e r e s t u d i e d a n d t h e r e f o r e , a r e n o t d e t a i l e d in t h i s report. T h i r t y - s e v e n n e p h r o s t o m y c a t h e t e r s (16 A B C , a n d 21 N B C ) w e r e p l a c e d in p a t i e n t s w i t h o u t c l i n i cal e v i d e n c e o f u r i n a r y t r a c t i n f e c t i o n ; 35 o f t h e s e w e r e in p a t i e n t s w i t h s t e r i l e u r i n e a t t h e t i m e o f i n s e r t i o n . In t h i s g r o u p t h e a v e r a g e d u r a t i o n o f c a t h e t e r p l a c e m e n t w a s 14 d a y s ( 1 - 4 9 d a y s ) f o r A B C
J.L. Nosher et at.: Antibiotic Bonded Nephrostomy
104 Table 3. Organisms isolated from nephrostomy urine specimens.
Number of times organism isolated per catheter Clinical Status of patient Study group
Bacteriuria ABC
NBC
Clinical UTI
Total
ABC
NBC
Total
Organisms Pseudomonas Klebsiella Serratia Citrobacter Proteus Acinetobacter E. coli Enterococcus Staphtococcus
Yeast Total
3 3 1 0 1 0 2 2 1
5 0 I 1 0 3 0 1 "~
8 3 2 1 [ 3 2 3 3
3 3 0 0 1 0 2 0 0
3 0 I 1 0 0 0 I 1
6 3 1 1 1 0 2 1 1
0 13
2 15
2 28
0 9
2 9
2 18
and 22.1 days (1-1 I0 days) for NBC. In patients with sterile urine, bacteriuria developed with seven of sixteen ABC (43.8%) and eight of nineteen NBC (42. I%). Patients with three of sixteen ABC (18.7%) and six of 21 NBC (28.6%) who initially did not have clinical UTI (including patients with two NBC who initially had bacteriuria) later developed clinical UTI. Clinical UTI developed at a median time of 23 days (1-49 days) with ABC and 29 days (3-51 days) with NBC. Considering all catheters, bacteriuria developed in 20, 50, and 80% of catheters by day 4, 13, and 19, respectively, after insertion. Antibiotic therapy was successful in treating all but one of the patients who developed clinical UTI. One patient with a NBC was unsuccessfully treated with antibiotics; another patient with bilateral nephrostomies was denied antibiotics and died of terminal carcinomatosis and UTI. The average duration of antibiotic administration required for elimination of UTI signs and s y m p t o m s was 7 days in both groups. There "were no statistically significant differences in the incidence or timing of bacteriuria or clinical UTI, or response to therapy of UTI when comparing the ABC and control groups. Eleven catheters were placed in patients who presented with clinical upper UTI before undergoing nephrostomy placement. Following percutaneous nephrostomy, all were successfully treated with antibiotics. None of these patients developed subsequent UTI. A patient with one catheter had persistent bacteriuria. The types of organisms isolated from urine of NBC did not appreciably differ from those isolated from ABC (Table 3). In both groups gram-negative organisms predominated. The organisms listed under Clinical U T I in Table 3 include both those from patients who presented with UTI and those who developed UTI following n e p h r o s t o m y insertion.
Table 4. Complications of nephrostomy Type of complication
% of catheters
Clinical UTI
24
Gross hematuria for greater than 24 h (none required transfusion)
6
Cutaneous infection at catheter insertion site Inadvertant catheter withdrawal, complete or incomplete
4 17
Catheter damage by patient or personnel Catheter occlusion
6 6
Minor bleeding at insertion site Total complications (some catheters were associated with more than one complication)
4 45.7
On removal, 8 of 14 ABC (57%) but none of 13 NBC that were examined had minimal encrustation (significance, P = 0.001). N o significant differences in catheter occlusion, incidence of clinical urinary tract infection, bacteriuria, or catheter tip infection were observed when comparing encrusted and nonencrusted catheters. Complications occurred with the use of 21 of 48 nephrostomy catheters (45.7%) and are listed in Table 4. These complications were not influenced by the type of catheter used.
Discussion
Percutaneous n e p h r o s t o m y is an effective method for relieving urinary tract obstruction, and gaining access to the urinary tract for interventional procedures. Though conventional wisdom is that tongterm complications of p e r c u t a n e o u s n e p h r o s t o m y , particularly infections, are frequent, there is little documentation of the incidence of these complications in the literature. The current study was performed to develop statistics on infectious complications of percutaneous n e p h r o s t o m y , and to determine the effectiveness of antibiotic bonded catheters in diminishing the incidence of UTI and catheter occlusion. Time of follow-up was not restricted so that the natural history of infectious complications might be studied. Approximately half of all patients with sterile urine at the time of n e p h r o s t o m y insertion developed bacteriuria within 2 weeks. The overall incidence of infection would probably have been greater except that m a n y catheters were r e m o v e d within the first 7 days following the procedure, accounting for most patients not developing bacteriuria. Within this group of patients, o v e r 80% of
J.L. Nosher et al.: Antibiotic Bonded Nephrostomy catheters in place for 20 days were associated with bacteriuria. In addition, clinical UTI developed with approximately 24% of percutaneous nephrostomy catheters in this group. All but 1 patient with clinical UTI (including patients with preexistent UTI at the time of nephrostomy) were effectively treated and their urine rendered sterile following appropriate antibiotic m a n a g e m e n t . The incidence of bacteriuria and U T I did not differ significantly when considering the first catheters inserted, reinserted catheters, and simultaneous contralateral catheters. The bonding of the antibiotic cefoxitin to nephrostomy catheters of the study group did not alter the incidence or the timing of onset of either bacteriuria or clinical U T I , nor did it alter the response of UTI to systemic antibiotic therapy when compared to the control group. In patients with ABC, organisms accounting for bacteriuria and clinical UT1 were sensitive to the antibiotic cefoxitin in 36% of cases. The types of organisms and their sensitivities did not differ in the NBC and ABC groups and therefore, the use of ABC did not lead to the selection of organisms resistant to the antibiotic, cefoxitin. The cationic bonding process limited the choice of available antibiotics to penicillins and cephalosporins, and of these agents, after retrospectively analyzing sensitivily results, cefoxitin was shown to be an effective choice of antibiotic, although p s e u d o m o n a s and enterococcus strains, u n c o m m o n pathogens in uncomplicated UTI, were frequently isolated. These organisms are uniformly resistant to cefoxitin, but it is unlikely that the results were affected as these organisms were seen in both groups but more frequently in the group with NBC. It is of interest that the only statistically significant difference in the data comparing the ABC and NBC groups was the incidence of catheter encrustation, seen only in patients with ABC. H o w e v e r . these encrustations did not appear to be of any clinical importance. No patient developed signs or s y m p t o m s of hypersensitivity to the antibiotic which was bonded to the ABC. Catheter maltunction has been thought to be a major contributor to UTI in patients with n e p h r o s t o m y . Catheter occlusion or malfunction was not a major factor contributing to infection in our patients. The majority of patients in our series had an underlying malignancy and these patients were found to have a greater incidence of clinical UTI when compared with patients with nonmalignant disease. This observation did not reach statistical significance probably because of the small sample sizes involved. In vitro testing of antibiotic retention to
105 T D M A C - c o a t e d catheters revealed a reduction of radiolabeled cefoxitin from 24 /zg/cm to 2 /xg/cm during 24 h of washing with urine. The cefoxitin concentration of 2/a,g/cm has been shown to be bacteriocidal to staph aureus in vitro. Previous studies have shown that stable concentrations of antibiotic remained on central vascular catheters and dialysis catheters when immersed in plasma and dialysis solution, respectively, following an initial rapid period of elution [8]. The in vitro testing does not address the antibiotic concentration on the catheter surface in the n e p h r o s t o m y tract. The antibiotic concentration would presumably be greater on the catheter surface where bacterial migration is believed to occur most often [4]. The fact remains, however, that failure of antibiotic bonded catheters to effect the incidence or onset of infectious complications of percutaneous n e p h r o s t o m y may be to a large degree related to insufficient antibiotic retention to the nephrostomy catheters. The overall incidence of complications in this series is high and reflects careful postprocedural evaluation of the paticnts. Gross hematuria and bleeding at the insertion site were minor complications of no clinical significance. Inadvertent catheter withdrawal, which occurred in 17% of the patients, was of much greater clinical concern, frequently occurring in the setting of a patient with diminished sensorium in a critical care bed. This occurred with both loop and nonloop catheters. Consideration should be given to insertion of loop catheters of large French size, and U-loop catheters in uncooperative, critical care patients. In addition, catheter damage or clogging with resultant malt'unction occurred in 12% of the patients. Catheter occlusion did not appear to be related to intraluminal encrustation. This study concludes that bonding of the antibiotic cefoxitin to percutaneous nephrostomy catheters did not influence the incidence of bacteriuria or UTI. There was a higher incidence of luminal debris in retrieved catheters coated with cefoxitin.
References I. Stables DP (1982) Percutaneous nephrostomy: Techniques, indications, and results. UrN Clin N Am 9:15-29 2. Lang EK, Price ET (1983) Redefinitio'ns of indications for percutaneous nephrostomy. Radiology 147:419-426 3. Ho PC, Talner LS, Parson CL, Schmidt JD (1980) Percutaneous nephrostomy: Experience in 107 kidneys. Urology 16:532-535 4. Bjornson HS. Colley R. Bower RH, Duty VP. SchwartzFulton JT. Fischer JE (1982) Association between microorganism growth at the catheter site and colonization of the catheter in patients receiving total parenteral nutrition. Surgery 92:720-726
106 5. Tooskin SZ, Harvey RA, Greco RS (1983) Prevention of catheter sepsis by antibiotic bonding. American College of Surgeons, 1983 Surgical Forum 34:132-133 6. Rodriguez JL, Trooskin SZ, Greco RS, Herbstman RA, Donetz AP, Harvey RA (1986) Reduced bacterial adherence to surfactant-coated catheters. Curr Surg 43:422-425 7. Trooskin SZ, Donetz AP, Baxter J, Harvey RA, Greco RS (1987) Infection-resistant continuous peritoneal dialysis catheters. Nephro 46:263-267 8. Trooskin SZ, Donetz AP, Harvey RA, Greco RS (1985) Pre-
J.L. Nosher et al.: Antibiotic Bonded Nephrostomy vention of catheter sepsis by" antibiotic bonding. Surgery 97(5):547-55 I 9. Trooskin SZ, Harvey RA, Kahn M, Lennard TWJ, Greco RS (in press) Results of a prospective clinical trial of antibiotic bonded catheters for continuous ambulatory peritoneal dialysis (CAPD). Book of Proceedings, 1V, Int Symposium on Peritoneal Dialysis 10. Greco RS, Harvey RH (1984) The biochemical bonding of cefoxitin to microporous polytetrafluoroethylene surface. J Surg Res 36:237-243
CardioVascular andInterventional Radiology 9 Springer-Verlag New York Inc. 1990
Antibiotic Bonded Nephrostomy Catheters for Percutaneous Nephrostomies John L. N o s h e r , J A l a n S. E r i c k s e n , ~ S t a n l e y Z. T r o o s k i n , 2 G a r y S. N e e d e l l , j R i c h a r d A. H a r v e y ) and R a l p h S. G r e c o : Departments of ~Radiology, :Surgery. and 3Biochemistry, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey. USA
A b s t r a c t . A p r o s p e c t i v e c o n t r o l l e d trial o f the effectiveness of a cefoxitin-bonded nephrostomy catheter was u n d e r t a k e n to d e t e r m i n e the e f f e c t i v e n e s s o f an a n t i b i o t i c b o n d e d c a t h e t e r in d e c r e a s i n g the infectious c o m p l i c a t i o n s o f p e r c u t a n e o u s n e p h r o s t o m y . The s t u d y c o n c l u d e s that b o n d i n g o f the antibiotic c e f o x i t i n to p e r c u t a n e o u s n e p h r o s t o m y cathe t e r s did not influence the i n c i d e n c e o f b a c t e r i u r i a o r u r i n a r y t r a c t infection. In additiQn, o b s e r v a t i o n s on the o v e r a l l i n c i d e n c e o f c o m p l i c a t i o n s from percutaneous nephrostomy are made.
Key words: A n t i b i o t i c b o n d e d c a t h e t e r - - P e r c u t a neous nephrostomy--Nephrostomy tion--lnfectious complication
complica-
bonded continuous ambulatory peritoneal dialysis (CAPD) catheters and vascular catheters have been s h o w n to be e f f e c t i v e in r e d u c i n g b a c t e r i a l c o l o n i z a tion a n d in i n c r e a s i n g r e s i s t a n c e to infection in animal m o d e l s [5-8]. P r e l i m i n a r y r e s u l t s o f a clinical trial h a v e d e m o n s t r a t e d d e c r e a s e d c a t h e t e r tract infection a n d p e r i t o n i t i s in p a t i e n t s r e c e i v i n g antibio t i c - b o n d e d C A P D c a t h e t e r s [9]. W i t h t h e s e r e s u l t s in mind, the c u r r e n t s t u d y was u n d e r t a k e n to i n v e s tigate the e f f i c a c y o f a p r o t o t y p e a n t i b i o t i c b o n d e d n e p h r o s t o m y c a t h e t e r in d i m i n i s h i n g the i n c i d e n c e . and d e l a y i n g the o n s e t o f b a c t e r i u r i a , s y m p t o m a t i c urinary tract infection, and catheter occlusion.
Materials and Methods In Vitro B o n d i n g o f A n t i b i o t i c to C a t h e t e r
P e r c u t a n e o u s n e p h r o s t o m y is a safe and effective m e t h o d for t r e a t m e n t o f o b s t r u c t i v e u r o p a t h y , for d i v e r s i o n o f urine f r o m the u r e t e r o r b l a d d e r , and for gaining a c c e s s to the u r i n a r y tract for i n t e r v e n tional p r o c e d u r e s . T h e p r o c e d u r e can be p e r f o r m e d s u c c e s s f u l l y in a l m o s t all p a t i e n t s , with few perip r o c e d u r a l c o m p l i c a t i o n s , but l o n g - t e r m c o m p l i c a tions including i n f e c t i o n , c a t h e t e r o c c l u s i o n , and d i s l o d g e m e n t a r e f r e q u e n t [1-3]. B j o r n s o n et al. [4] h a v e d e m o n s t r a t e d that bacterial m i g r a t i o n f r o m the skin a l o n g c a t h e t e r surfaces is m o r e significant in the i n f e c t i o n o f i n t r a v e nous catheters than is hematogenous c o n t a m i n a t i o n ; this o b s e r v a t i o n led to the d e v e l o p ment of antibiotic bonded catheters. Antibiotic-
Address reprint requests to: John L. Nosher, M.D., Department of Radiology. UMDNJ-Robert Wood Johnson Medical School, One Robert Wood Johnson Place - CN 19, New Brunswick, New Jersey 08903-0~)19, USA
Greco and Harvey [10] have previously described the binding of cefoxitin to polytetraflouroethytene coated with tridodecylmethyl-ammonium chloride tTDMAC). As part of the current study, the bonding and retention of antibiotic on polyethylene nephrostomy catheters was tested in uitro using ~4C-cefoxitin. One centimeter pieces of 10 French nephrostomy catheters were incubated with an aqueous solution of ~4C-cefoxitin (10 mg/cc) for 30 rain. The samples were washed five times in water and counted in a liquid scintillation counter to determine the retention of radiolabeled antibiotic. These samples were then incubated with vigorous stirring in human urine for 24 h in vitro and counted for radiolabeled antibiotic activity. Clinical Trial
Patients were eligible for this study if a percutancous nephrostomy catheter was clinically indicated for any reason and there was no history of hypersensitivity to the cephalosporin antibiotic cefoxitin, which was bonded to the experimental catheters. Twenty-two antibiotic bonded catheters (ABC) were placed in 17 patients and 26 nonbonded catheters (NBC) were placed in 18 patients. The average age of patients with ABC was 60 years (range 32-78) and of patients with NBC 59 years (range 8-80).
J.L. Nosher et al.: Antibiotic Bonded Nephrostomy Table 1. Underlying disease of patients and indication for nephrostomy
103 Table 2. Criteria for diagnosis of uJ-inary tract infection Bacteriuria of greater than 10.000 colony count (see text)
Indication
No. catheters (ABC, NBC)
Urinary obstruction (total) Due to malignancy Prostate CA Bladder CA Gynecologic CA Metastatic colon CA Metastatic breast CA Due to calculus Due to congenital anomaly Bladder hematoma Ureteral tuberculosis
43 (19,241 32 (15,17) 11 (6,5) 7 (3.4) 6 (3,3l 5 (1.4) 3 (2.1) 6 (3,3} 3 (I.2) I (0,1 ) 1 10, I )
UTI coexistent with obstruction due to any of the above
I1 (6,5/
Stone extraction (not obstructed)
3 (1 2}
Diversion for ureteral trauma
2 (2,0)
Total
48 (22,26)
Pyuria -> 10 white blood cells per high power field in unspun specimen Fever -> 100~ F in the absence of any other source of infection Abnormal white blood count (WBC) WBC ~ 10.000 with differential shift in the immunocompetent patient or Differential shift with or without WBC -> 10,000 in the immunocompromised patient, i.e., recent corticosteroid therapy or immunosuppressive chemotherapy
holding medium, and sent for culture, colony count, and organism identification. Stastical analysis of data included product survival analysis method for comparison of bacleriuria and UT1 in bonded versus control catheters. Fischer's exact test was used in the total population to evaluate the relationship of infection with other factors, including underlying disease.
ABC = Antibiotic bonded catheters; NBC = nonbonded catheters
Results Nine ABC and 10 NBC were placed in male patients and eight ABC and eight NBC were inserted in female patients. Indication for the nephrostomies and major cfitegories of underlying disease are listed in Table 1. Percutaneous nephrostomy was performed with the Seldinger technique utilizing ultrasound and fluoroscopic guidance. Catheters were randomly assigned to be either antibiotic bonded with cefoxitin (ABC) or to be nonbonded {NBC), serving as the experimental group and the control group. respectively. Several patients in the study were unable to give informed consent tbr the use of an ABC, and therefore, were assigned to an NBC which was outside the protocol sequence. Catheters used in the study were 8 or 10 French polyethylene pig-tailed or loop catheters. ABC catheters pretreated with the cationic surfactant 5% TDMAC in 95% ethanol were inserted into the patient. Urine was aspirated through the percutaneous access needle from the collecting system at the time of initial puncture and sent for culture. Routine culture was then performed on postinsertion days 1, 3, 7, 14 and thereafter, at 14-day intervals. Additional urine specimens were Obtained when the clinical status of the patient indicated the possibility of urinary tract infection. For the current study, a patient was designated as having bacteriuria if greater than 10,000 colony count was cultured from nephrostomy urine. Organisms from urine and catheter tips were identified, and correlated with the existence of possible clinical upper urinary tract infection (UTI). The criteria required for the diagnosis of clinical urinary tract infection are included in Table 2. Infrequently. a positive urine culture was not obtained from a patient with clinical upper UT[ which preceded nephrostomy who had received several days of systemic antibiotic therapy. In all other cases the patient with clinical UTI had culture-proven bacteriuria. A positive response of patients with clinical urinary tract infection to systemic antibiotic therapy was defined as resolution of the previously described criteria for clinical UTI. Complications of percutaneous nephrostomy other than urinary infection were also recorded. The protocol was completed when the nephrostomy catheter was removed for any reason. Upon removal of the catheter, the tip was inspected for any superficial or luminal debris termed "'encrustations" that may have accumulated. Under sterile conditions, each catheter tip was severed, placed in a microbial
In V i t r o Bonding o f Antibiotic to Catheter A f t e r s o a k i n g in r a d i o l a b e l e d L4C-cefoxitin s o l u t i o n a n d w a s h i n g in w a t e r , t h e s a m p l e s o f T D M A C treated catheters bound 24 beg c e f o x i t i n / c m , w h e r e a s u n t r e a t e d c a t h e t e r s r e t a i n e d l e s s t h a n 0.1 p , g / c m . F o l l o w i n g in vitro i n c u b a t i o n in h u m a n u r i n e f o r 24 h, T D M A C c a t h e t e r s r e t a i n e d 2 p,g o f cefoxitin/cm. This concentration of antibiotic has b e e n p r e v i o u s l y s h o w n in o u r l a b o r a t o r y t o b e b a c t e r i o c i d a l a g a i n s t Staph aureus in vitro.
Clinical Trial Forty-eight percutaneous nephrostomy catheters w e r e p l a c e d in 27 p a t i e n t s : 7 h a d b i l a t e r a l , s i m u l t a neous nephrostomies and 20 h a d s u c c e s s i v e nephrostomies or catheter replacements. The unit o f o b s e r v a t i o n f o r p u r p o s e s o f a n a l y s i s in t h i s s t u d y was each nephrostomy catheter. A separate analysis o f f i r s t c a t h e t e r s i n s e r t e d in e a c h r e n a l u n i t , w a s c o m p a r e d w i t h r e s u l t s f r o m all c a t h e t e r s t o e v a l u a t e the possibility of bias due to successive nephrostomy and catheter reinsertion. These results did not s i g n i f i c a n t l y d i f f e r f r o m r e s u l t s w h e n all c a t h e t e r s w e r e s t u d i e d a n d t h e r e f o r e , a r e n o t d e t a i l e d in t h i s report. T h i r t y - s e v e n n e p h r o s t o m y c a t h e t e r s (16 A B C , a n d 21 N B C ) w e r e p l a c e d in p a t i e n t s w i t h o u t c l i n i cal e v i d e n c e o f u r i n a r y t r a c t i n f e c t i o n ; 35 o f t h e s e w e r e in p a t i e n t s w i t h s t e r i l e u r i n e a t t h e t i m e o f i n s e r t i o n . In t h i s g r o u p t h e a v e r a g e d u r a t i o n o f c a t h e t e r p l a c e m e n t w a s 14 d a y s ( 1 - 4 9 d a y s ) f o r A B C
J.L. Nosher et at.: Antibiotic Bonded Nephrostomy
104 Table 3. Organisms isolated from nephrostomy urine specimens.
Number of times organism isolated per catheter Clinical Status of patient Study group
Bacteriuria ABC
NBC
Clinical UTI
Total
ABC
NBC
Total
Organisms Pseudomonas Klebsiella Serratia Citrobacter Proteus Acinetobacter E. coli Enterococcus Staphtococcus
Yeast Total
3 3 1 0 1 0 2 2 1
5 0 I 1 0 3 0 1 "~
8 3 2 1 [ 3 2 3 3
3 3 0 0 1 0 2 0 0
3 0 I 1 0 0 0 I 1
6 3 1 1 1 0 2 1 1
0 13
2 15
2 28
0 9
2 9
2 18
and 22.1 days (1-1 I0 days) for NBC. In patients with sterile urine, bacteriuria developed with seven of sixteen ABC (43.8%) and eight of nineteen NBC (42. I%). Patients with three of sixteen ABC (18.7%) and six of 21 NBC (28.6%) who initially did not have clinical UTI (including patients with two NBC who initially had bacteriuria) later developed clinical UTI. Clinical UTI developed at a median time of 23 days (1-49 days) with ABC and 29 days (3-51 days) with NBC. Considering all catheters, bacteriuria developed in 20, 50, and 80% of catheters by day 4, 13, and 19, respectively, after insertion. Antibiotic therapy was successful in treating all but one of the patients who developed clinical UTI. One patient with a NBC was unsuccessfully treated with antibiotics; another patient with bilateral nephrostomies was denied antibiotics and died of terminal carcinomatosis and UTI. The average duration of antibiotic administration required for elimination of UTI signs and s y m p t o m s was 7 days in both groups. There "were no statistically significant differences in the incidence or timing of bacteriuria or clinical UTI, or response to therapy of UTI when comparing the ABC and control groups. Eleven catheters were placed in patients who presented with clinical upper UTI before undergoing nephrostomy placement. Following percutaneous nephrostomy, all were successfully treated with antibiotics. None of these patients developed subsequent UTI. A patient with one catheter had persistent bacteriuria. The types of organisms isolated from urine of NBC did not appreciably differ from those isolated from ABC (Table 3). In both groups gram-negative organisms predominated. The organisms listed under Clinical U T I in Table 3 include both those from patients who presented with UTI and those who developed UTI following n e p h r o s t o m y insertion.
Table 4. Complications of nephrostomy Type of complication
% of catheters
Clinical UTI
24
Gross hematuria for greater than 24 h (none required transfusion)
6
Cutaneous infection at catheter insertion site Inadvertant catheter withdrawal, complete or incomplete
4 17
Catheter damage by patient or personnel Catheter occlusion
6 6
Minor bleeding at insertion site Total complications (some catheters were associated with more than one complication)
4 45.7
On removal, 8 of 14 ABC (57%) but none of 13 NBC that were examined had minimal encrustation (significance, P = 0.001). N o significant differences in catheter occlusion, incidence of clinical urinary tract infection, bacteriuria, or catheter tip infection were observed when comparing encrusted and nonencrusted catheters. Complications occurred with the use of 21 of 48 nephrostomy catheters (45.7%) and are listed in Table 4. These complications were not influenced by the type of catheter used.
Discussion
Percutaneous n e p h r o s t o m y is an effective method for relieving urinary tract obstruction, and gaining access to the urinary tract for interventional procedures. Though conventional wisdom is that tongterm complications of p e r c u t a n e o u s n e p h r o s t o m y , particularly infections, are frequent, there is little documentation of the incidence of these complications in the literature. The current study was performed to develop statistics on infectious complications of percutaneous n e p h r o s t o m y , and to determine the effectiveness of antibiotic bonded catheters in diminishing the incidence of UTI and catheter occlusion. Time of follow-up was not restricted so that the natural history of infectious complications might be studied. Approximately half of all patients with sterile urine at the time of n e p h r o s t o m y insertion developed bacteriuria within 2 weeks. The overall incidence of infection would probably have been greater except that m a n y catheters were r e m o v e d within the first 7 days following the procedure, accounting for most patients not developing bacteriuria. Within this group of patients, o v e r 80% of
J.L. Nosher et al.: Antibiotic Bonded Nephrostomy catheters in place for 20 days were associated with bacteriuria. In addition, clinical UTI developed with approximately 24% of percutaneous nephrostomy catheters in this group. All but 1 patient with clinical UTI (including patients with preexistent UTI at the time of nephrostomy) were effectively treated and their urine rendered sterile following appropriate antibiotic m a n a g e m e n t . The incidence of bacteriuria and U T I did not differ significantly when considering the first catheters inserted, reinserted catheters, and simultaneous contralateral catheters. The bonding of the antibiotic cefoxitin to nephrostomy catheters of the study group did not alter the incidence or the timing of onset of either bacteriuria or clinical U T I , nor did it alter the response of UTI to systemic antibiotic therapy when compared to the control group. In patients with ABC, organisms accounting for bacteriuria and clinical UT1 were sensitive to the antibiotic cefoxitin in 36% of cases. The types of organisms and their sensitivities did not differ in the NBC and ABC groups and therefore, the use of ABC did not lead to the selection of organisms resistant to the antibiotic, cefoxitin. The cationic bonding process limited the choice of available antibiotics to penicillins and cephalosporins, and of these agents, after retrospectively analyzing sensitivily results, cefoxitin was shown to be an effective choice of antibiotic, although p s e u d o m o n a s and enterococcus strains, u n c o m m o n pathogens in uncomplicated UTI, were frequently isolated. These organisms are uniformly resistant to cefoxitin, but it is unlikely that the results were affected as these organisms were seen in both groups but more frequently in the group with NBC. It is of interest that the only statistically significant difference in the data comparing the ABC and NBC groups was the incidence of catheter encrustation, seen only in patients with ABC. H o w e v e r . these encrustations did not appear to be of any clinical importance. No patient developed signs or s y m p t o m s of hypersensitivity to the antibiotic which was bonded to the ABC. Catheter maltunction has been thought to be a major contributor to UTI in patients with n e p h r o s t o m y . Catheter occlusion or malfunction was not a major factor contributing to infection in our patients. The majority of patients in our series had an underlying malignancy and these patients were found to have a greater incidence of clinical UTI when compared with patients with nonmalignant disease. This observation did not reach statistical significance probably because of the small sample sizes involved. In vitro testing of antibiotic retention to
105 T D M A C - c o a t e d catheters revealed a reduction of radiolabeled cefoxitin from 24 /zg/cm to 2 /xg/cm during 24 h of washing with urine. The cefoxitin concentration of 2/a,g/cm has been shown to be bacteriocidal to staph aureus in vitro. Previous studies have shown that stable concentrations of antibiotic remained on central vascular catheters and dialysis catheters when immersed in plasma and dialysis solution, respectively, following an initial rapid period of elution [8]. The in vitro testing does not address the antibiotic concentration on the catheter surface in the n e p h r o s t o m y tract. The antibiotic concentration would presumably be greater on the catheter surface where bacterial migration is believed to occur most often [4]. The fact remains, however, that failure of antibiotic bonded catheters to effect the incidence or onset of infectious complications of percutaneous n e p h r o s t o m y may be to a large degree related to insufficient antibiotic retention to the nephrostomy catheters. The overall incidence of complications in this series is high and reflects careful postprocedural evaluation of the paticnts. Gross hematuria and bleeding at the insertion site were minor complications of no clinical significance. Inadvertent catheter withdrawal, which occurred in 17% of the patients, was of much greater clinical concern, frequently occurring in the setting of a patient with diminished sensorium in a critical care bed. This occurred with both loop and nonloop catheters. Consideration should be given to insertion of loop catheters of large French size, and U-loop catheters in uncooperative, critical care patients. In addition, catheter damage or clogging with resultant malt'unction occurred in 12% of the patients. Catheter occlusion did not appear to be related to intraluminal encrustation. This study concludes that bonding of the antibiotic cefoxitin to percutaneous nephrostomy catheters did not influence the incidence of bacteriuria or UTI. There was a higher incidence of luminal debris in retrieved catheters coated with cefoxitin.
References I. Stables DP (1982) Percutaneous nephrostomy: Techniques, indications, and results. UrN Clin N Am 9:15-29 2. Lang EK, Price ET (1983) Redefinitio'ns of indications for percutaneous nephrostomy. Radiology 147:419-426 3. Ho PC, Talner LS, Parson CL, Schmidt JD (1980) Percutaneous nephrostomy: Experience in 107 kidneys. Urology 16:532-535 4. Bjornson HS. Colley R. Bower RH, Duty VP. SchwartzFulton JT. Fischer JE (1982) Association between microorganism growth at the catheter site and colonization of the catheter in patients receiving total parenteral nutrition. Surgery 92:720-726
106 5. Tooskin SZ, Harvey RA, Greco RS (1983) Prevention of catheter sepsis by antibiotic bonding. American College of Surgeons, 1983 Surgical Forum 34:132-133 6. Rodriguez JL, Trooskin SZ, Greco RS, Herbstman RA, Donetz AP, Harvey RA (1986) Reduced bacterial adherence to surfactant-coated catheters. Curr Surg 43:422-425 7. Trooskin SZ, Donetz AP, Baxter J, Harvey RA, Greco RS (1987) Infection-resistant continuous peritoneal dialysis catheters. Nephro 46:263-267 8. Trooskin SZ, Donetz AP, Harvey RA, Greco RS (1985) Pre-
J.L. Nosher et al.: Antibiotic Bonded Nephrostomy vention of catheter sepsis by" antibiotic bonding. Surgery 97(5):547-55 I 9. Trooskin SZ, Harvey RA, Kahn M, Lennard TWJ, Greco RS (in press) Results of a prospective clinical trial of antibiotic bonded catheters for continuous ambulatory peritoneal dialysis (CAPD). Book of Proceedings, 1V, Int Symposium on Peritoneal Dialysis 10. Greco RS, Harvey RH (1984) The biochemical bonding of cefoxitin to microporous polytetrafluoroethylene surface. J Surg Res 36:237-243
