Journal of Antimicrobial Chemotherapy (1990) 26, Suppl. A, 77-83

Antibiotic prophylaxis with cefotaxime in endoscopic extraction of upper urinary tract stones: a randomized study R. O. Foorcade and the Cefotaxime Cooperative Group*

This French multicentre, placebo-controlled, double-blind study investigated the efficacy of a single dose of cefotaxime 1 g iv in the prophylaxis of patients undergoing endoscopic extraction of urinary tract stones. Postoperative fever occurred in 12 patients in the placebo group and in nine in the cefotaxime group (no significant difference). The incidence of postoperative bacteriuria, between the first and third postoperative day, was significantly higher in the placebo group (15/60, 25%) than in the cefotaxime group (5/60, 8-5%). This controlled study clearly demonstrates the efficacy of antibiotic prophylaxis in endourological procedures. Cefotaxime significantly reduced the incidence of early postoperative bacteriuria without causing any significant side effects. Introduction

Most general reviews of antibiotic prophylaxis in urological procedures advocate its use primarily for patients undergoing transurethral surgery of the prostate (Larsen, Gasser & Madsen, 1986; Gattegno, 1987), although others consider its use to be controversial (Grabe, 1987). The issue of the use of prophylaxis for endoscopic surgery is even more confused. As Scherz & Parsons (1987) stated in a general review, "No controlled study addresses the role of prophylactic antibiotics for extracorporeal shock wave lithotripsy or endoscopic surgery of stones". Since stone extraction is considered to be a 'clean contaminated' procedure, (Childs, 1983) and it has been shown that 70% of branched stones may be infected with various bacteria, primarily Proteus spp. (Fowler, 1984), there is a rationale for the use of prophylactic antibiotics in these procedures. In addition, clinical studies show a high rate of postoperative bacteriuria and fever after percutaneous extraction of stones (Charton etal., 1986). Various prophylactic regimens can be used. On the basis of the work of Hargreave et al. (1982) and Botto et al. (1984), cefotaxime in a 1 g single intravenous dose, given at induction of anaesthesia, was chosen for this study, which aimed to investigate the efficacy of this regimen in the prophylaxis of patients undergoing endoscopic urinary stone extraction procedures. *Cefotajime Cooperative Group: J. Biserte (Lille), J. P. Boiteux (Clermont-Ferrand), J. Chailley (Tours), P. Colombel (Le Mans), F. Duval (Reims), R. O. Fourcade (Aiuerre), P. Grise (Rouen), L. Lanay (Juvisy), B. Le Portz (Vannes), P. Mangin (Brest), J. P. Mignard (St-Brieuc), C. Mugnier (Bruges), M. Petit (Reims), J. Tremaux (Dijon), C. Viville (Strasbourg). 77 0305-7453/90/26A077 + 07 $02.00/0

©1990 The British Society for Antimicrobial Chemotherapy

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Department of Urology, Centre Hdpitalier d'Auxerre, France


R. O. Foarcade et al Patients and methods

This placebo controlled, double-blind study involved 14 urological centres throughout France. All patients aged between 18 and 60 years of age, undergoing endoscopic extraction of upper urinary tract stones, over a one year period, were included in the study. Patients with a history of allergic reactions (cutaneous or other) to any /f-lactam antibiotic, a documented bacteriuria in the month prior to the endoscopic procedure, antibiotic therapy in the month prior to study entry, or a previous second stage percutaneous nephrolithotomy procedure were excluded from entry to the study.

Two types of surgical procedure were employed: percutaneous nephrolithotomy (PCNL) and ureterorenoscopy (URS). In the PCNL procedure, a ureteral stent was inserted in the renal pelvis and a percutaneous tract was dilated up to 26 F to allow insertion of a nephroscope. The stone was approached through this tunnel and either removed or destroyed by ultrasonic or electrohydraulic means. Drainage was ensured by nephrostomy, and the ureteral stent was removed at the end of the procedure. In URS, a transurethral transureteral approach to the stone through the insertion of a ureteroscope was employed. After dilatation of the ureteral meatus, the stone was basketted and removed or destroyed under visual control. Drainage, if any, consisted of a ureteral stent and bladder catheter, or an indwelling autostatic ureteral stent.

Drug treatment Patients entering the study were randomly assigned to receive a single intravenous dose of either cefotaxime 1 g, or placebo, at induction of anaesthesia. All patients had urine specimens taken on the day before the operation. Only patients with sterile urine were included in the study.

Assessment criteria Bacteriological study of the stone was initially done, but the frequent use of ultrasonic stone destruction and aspiration of fragments in a non-sterile vacuum bottle hindered its application. As complete bacteriological analysis was carried out on less than 25% of stones; these results are not included. The results of treatment were therefore assessed on two major criteria. The first was the presence of significant bacteriuria ( > 103cfu/ml) in any of the urine samples obtained daily between the first day and third day. Samples tested were from midstream voided urine and any drainage catheter (nephrostomy tube, ureteral stent, bladder catheter). The second was the presence of fever, defined as a temperature over 38°C, on any of the first three postoperative days.

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Surgical procedures

Prophylaxis in npper minary tract stone extraction


Table I. Demographic characteristics Cefotaxime (B-60)

Total mean (n = 120)

44-6 ±15-5

46-5 ±14-7


73-3 67-9 ± 1 0 2

7(H) 70-2 ±12-6

71-7 69-1 ±11-5




450 2(M) 10-5

46-6 15-6 211

45-8 17-8 15-8

Postoperatively, patients were followed up to day 30. Clinical infection, where it occurred, was noted during the day 3 to day 30 period, and urine culture was repeated at day 30. Adverse drug reactions were also observed. Qualitative data were evaluated with the chi-squared test. Student's f-test and Fisher's exact test were used to compare the differences between the groups. Table n. Type and location of stones Cefotaxime (« = 60)

Placebo (« = 60)

Unilateral stone (%) Operated side left (%) Single stone (%) Upper tract dilatation (%) Stone location (number of cases) calyx pelvis junction ureter staghorn Type of stone (%) oxalate uric acid struvite fibrin •Ureterorenojcopy. ^Percutaneous nephrolithotomy.

URS* („ « 38)

PCNL' (/» = 22)

URS* (n = 33)

PCNL* (n - 27)





57-9 94-7

63-6 90-9

45-5 84-8

59-3 77-8





1 — — 34 4

7 11 3 5 —

3 — — 27 9

8 17 3 6 —

77-8 7-4 111 3-7

63-2 5-3 31-6 —

81-5 7-4 11-1 —

75 5 20 —

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Age in years (mean±s.D.) Sex: male (%) Weight in kg (mean±s.D.) Unilateral stone (%) Previous presence of stone (%) one month one year Previous surgery (%)

Placebo (n = 60)


R. O. Foorcade et aL Table IIL Description of surgical procedures Cefotaxime

Placebo PCNL* = 22)

URS* (« = 38)


= 33)

PCNL* (" = 27)















31 5




•Ureterorenoscopy. 'Percutaneous nephrolithotomy.

Results Of the 147 patients entering the study, 120 patients were eligible for analysis (60 in the CTX group and 60 in the placebo group). Twenty-seven patients were excluded from the analysis because of the following factors: insufficient clinical data (five cases), unexpected preoperative bacteriuria (seven cases), or failure of endoscopic procedure (15 cases, nine being ureterorenoscopy). The patients' characteristics are summarized in Table I. The type and location of stones extracted are listed in Table II. The surgical procedures performed are outlined in Table III. There were no significant differences with respect to patient characteristics, type of stone, or complications in the surgical procedure between the cefotaxime and the placebo group. The incidence of postoperative bacteriuria between the first and third postoperative days was significantly higher in the placebo group than in the cefotaxime group Table IV. Treatment results No. of patients (%) placebo group (« - 60)

cefotaxime group (n = 60)

12 (20)



15(25) 0(0)

5(8-5) 0(0)


6(10) 1(1-6)

Assessment criteria Postoperative fever Infectious episodes 0-3 days Other infections 3-30 days Other infections

0(0) 0(0)

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Time for placement of pelvic catheter (min) Time for dilatation (tract or orifice) (min) Time for stone extraction (min) Total procedure (min) Complications in surgical procedure (%)


Prophylaxis in upper urinary tract stone extraction


Table V. Positive urine cultures obtained in the early postoperative period (day one to day three) Positive urine cultures (number of cases (%)) Surgical procedure




8(13) 15(25)-

2 (3-5)


"Difference between placebo and cefotaxime group statistically significant at P -= 0014 (chi-jquared test).

(P = 0-014) (Table IV). Analysis according to the type of surgical procedure used also showed a lower incidence of bacteriuria in the cefotaxime group (Table V). However, this analysis resulted in groups too small for statistical significance to be reached. Sixteen different isolates were cultured in the placebo group and five in the cefotaxime group (Table VI). In the placebo group, two strains were resistant to cefotaxime and ten strains were sensitive, while in the cefotaxime group, two strains were resistant to cefotaxime and one sensitive (Escherichia coli). The remaining strains were either not tested or found to be of intermediate sensitivity. Fever occurred in 12 patients in the placebo group and nine in the cefotaxime group (Table TV). Fever did not always correlate with early postoperative infection. Only seven of the 12 febrile placebo patients and only four of the nine febrile cefotaxime treated patients had infected urine. In seven of the remaining patients, pyrexia was caused by transient renal haematoma (five cases), acute bronchitis (one case), and venous puncture site inflammation (one case). In three cases no cause was found. Chemical stone type had no influence on the outcome of postoperative infection. Infection after extraction of struvite stones, which were likely to be infected, was found in two of nine patients in the placebo group, and one of seven patients in the cefotaxime group. Table VI. Bacterial isolates Bacterium Gram-negative Escherichia coli Proteus spp. Pseudomonas spp. Enterobacter spp. Acinetobacter spp. Gram-positive Staphylococcus spp. Staph. aweus Streptococcus spp.

Placebo group

Cefotaxime group

5 1 1 1 —

1 — 1 — 2

5 1 2


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Percutaneous nephrolithotomy (n = 49) Urcterorenoscopy («"=) Total



R. O. Foorcade el al

Discussion In percutaneous surgery for stone extraction, without antibiotic prophylaxis, raised temperature has been reported in approximately 10% of cases (Charton etal., 1986) and urinary tract infection in up to 35% of cases. However, the use of prophylaxis has been advocated in the open extraction of stones and endoscopic surgery (Heinz, Hoffler & Koeppl, 1983). Prophylaxis in these procedures has been shown to reduce the incidence of bacteriuria to as low as 2% to 3% (Clayman & Castaneda-Zuniga, 1984; Taii7in-Fin etal., 1986). Unfortunately, these studies were not controlled. With an early postoperative infection rate of 25% in the placebo group as against 8-3% in the cefotaxime treated group (P 0-014), the results of this controlled study clearly favour the use of antibiotic prophylaxis. The choice of a long-acting antibiotic, such as cefotaxime, allows a single 1 g iv dose, given at induction of anaesthesia, to be used. Cefotaxime provides complete prophylactic antibiotic cover at a lower cost and with less inconvenience than other procedures using multiple injections (Charton etal., 1984; Botto, 1989). The effectiveness of a single cefotaxime dose is shown since only two bacteria sensitive to cefotaxime were isolated in the cefotaxime group. Cefotaxime was chosen as the incidence of strains resistant to cefotaxime in the French urologjcal units involved in the study was low: only four strains (two in the placebo group, two in the cefotaxime group) cultured in postoperative urine were resistant to cefotaxime: Staphylococcus aureus (1), Acinetobacter spp. (2) and Pseudomonas spp. (1). An alternative technique to antibiotic prophylaxis, using nephrostomy tube irrigation with a solution of noxythiolin, has recently been reported from England (Buck, 1988). Although the bacteriological results are comparable, the choice of agent and cost effectiveness of such a procedure (only intended for PCNL and not suitable for URS) remain to be evaluated. This French multicentre controlled study showed that antibiotic prophylaxis using a single intravenous dose of 1 g of cefotaxime at the start of endoscopic urinary tract stone extraction procedures provided effective antibiotic prophylaxis and achieved a significant reduction in early postoperative bacteriuria, without any significant side-effects.

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During the day 3 to day 30 follow-up period, no infectious symptoms occurred in the cefotaxime group, while seven infectious episodes were noted in the placebo group: six urinary tract infections (three asymptomatic with bacteriuria, two with flank pain and one prostatitis without detectable bacteriuria) and one respiratory tract infection; one patient with bronchitis also had bacteriuria. Only three patients had an early postoperative urinary tract infection. In two cases, infection was caused by the same bacterial strain as isolated in the immediate post-operative period. In the third case, whilst a Pseudomonas strain was isolated in the initial postoperative period (treated with cefotaxime), an Acinetobacter strain was isolated in the follow-up period. No major side-effects were noted. Only two mild skin rashes were noted in the cefotaxime group.

Prophylaxis in upper urinary tract stone extraction



North America 14, 265—71.

Tauzin-Fin, P., Ragnaud, J. M., Ballanger, P., Pcrrier, R. & Sabathie, M. (1986). Etude comparative de la cefoperazone et du cotrimoxazole dans la chirurgie lithiasique renale par voie per-cutanee. Pathologie Biologic 34, 498-501.

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Botto, H., Richard, F., Mathieu, F., Perrcau, A. M. & Carney, M. (1984). Short-term prophylaxis with cefotaxime in prostatic surgery. Journal of Antimicrobial Chemotherapy 14, Suppl. B, 231-5. Buck, A. C. (1988). The use of noxythiolin (Noxyflex 'S') as an antiseptic irrigant in upper urinary tract drainage following percutaneous nephrolithotomy. British Journal of Urology 62, 306-10. Charton, M., Dosne, B., Escovar, P., Kopf, A. & Brisset, J. M. (1984). Traitement prophylactique minute des infections urinaires apres resection endoscopique de la prostate Presse Medicale 13, 545-7. Charton, M., Vallancien, G., Veillon, B. & Brisset, J. M. (1986). Urinary tract infection in percutaneous surgery for renal calculi. Journal of Urology 135, 15-7. Childs, S. J. (1983). Genitourinary surgical prophylaxis. Infections in Surgery 2, 701-10. dayman, R. V. & Castafieda-Zuniga, W. R. (1984). Techniques in Endourology. Year Book Medical Publishers, Chicago, IL. Fowler, J. E. (1984). Bacteriology of branched renal calculi and accompanying urinary tract infection. Journal of Urology 131, 213-5. Gattegno, B. (1987). Antibiotherapie prophylactique en urologie. Annales d'Urologie 21, 75-9. Grabe, M. (1987). Antimicrobial agents in transurethral prostatic resection. Journal of Urology 138, 245-52. Hargreave, T. B., Hindmarsh, J. R., Elton, R., Chisholm, G. D. & Gould, J. C. (1982). Short-term prophylaxis with cefotaxime for prostatic surgery. British Medical Journal 284, 1008-10. Heinz, A., Hoffler, D. & Koeppe, P. (1983). Perioperative Antibiotikaprophylaxe bei obstmierender Nephrolithiasis. Aktuelle Urologie 14, 136-40. Larsen, E. H., Gasser, T. C. & Madsen, P. O. (1986). Antimicrobial prophylaxis in urologie surgery. Urologie Clinics of North America 13, 591-604. Scherz, H. C. & Parsons, C. L. (1987). Prophylactic antibiotics in urology. Urologie Clinics of

Antibiotic prophylaxis with cefotaxime in endoscopic extraction of upper urinary tract stones: a randomized study. The Cefotaxime Cooperative Group.

This French multicentre, placebo-controlled, double-blind study investigated the efficacy of a single dose of cefotaxime 1 g iv in the prophylaxis of ...
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