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MICROBIOLOGICAL STUDY OF BLADDER TUMORS, THEIR HISTOLOGY AND INFECTIVE COMPLICATIONS

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D. E BADENOCH, D.M., M.CH., ER.C.S. D. A. MURDOCH, M.Sc., M.B., B.S. R. C. TIPTAFT, E R. C.S. From the Departments of Urology and Medical Microbiology, The London Hospital, London, England

microbiology of bladder tumors and the infective complications of transurethraI t were studied prospectively in 51 patients. Patients taking antimicrobials were ith significant preoperative bacteriuria were included in the study when results urine specimen were unavailable at the time of operation. Infected tumors were nt of males and 75 percent of females. A wide range of bacteria, including fated; when streptococci or coliforms were cultured from the tumor, they were ~nificant numbers in the preoperative urine specimen. Perioperative bacteremia complications requiring parenteral antibiotics were more common in females h significant preoperative bacteriuria. No correlation was found between tumor 'ogic grade or stage of tumor. Patients with sterile preoperative urine and positive :tom tumors were no more likely to have postoperative urinary tract infections gative tumor cultures.

the microbiology of bladder iced conflicting evidence on tumor infection1.2; the rela)r histology has not been in~spective study compares the 1 the histologic grade and and the clinical course of the

(aged 64-86 years, median 70); none had been catheterized nor had received antimicrobials in the week before operation. During the study period, 12 males and 4 females already taking antimicrobials were admitted for transurethral resection of bladder tumor (TURBT); these patients were excluded. All patients had histologically proved transitional cell carcinoma of the bladder, except for one male with a nephrogenic adenoma. Tumors were staged and graded according to the UICC classification (UICC, i978). A Foley catheter was inserted at operation in 28 men (80 % ) and 11 women (60 %), and was usually removed the following day.

~nifieant preoperative bacte~xcluded from other studies; be at risk of postoperative tieularly as the result of the culture is not always avail,peration. This study excludes taking antimierobial agents to have bacteriuria prets with preoperative bactethe time of operation have

Specimen collection Bladder tumors were removed under sterile conditions by diathermy loop resection, placed in sterile Universal containers and transported immediately to the laboratory. Two blood samples were taken, in operating theater or in recovery, fifteen minutes and two hours after the start of tumor resection.

:al and Methods lied consisted of 35 males median 68) and 16 females ~.Y 1990

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Grade and stage of tumors

TABLEI. Tumor

Sex

--.Grade G2 G1

, G3

Ta

T1

-Stage T2

T3

T4

Tote1

Males* Total Infected

10 1

15 2

9 2

18 2

10 2

5 0

1 1

0 0

34 5

Females Total Infected

5 4

5 3

6 5

9 7

2 0

3 3

1 1

1 1

16 12

*One male patient with a nephrogenic adenoma is not included.

A clean-catch midstream specimen of urine was collected on the day before operation. A second specimen from the day after operation was usually a catheter specimen taken directly from the catheter by needle puncture. A third specimen, taken seven days after operation or on the day of discharge, was a mid-stream specimen.

Processing o] tumor specimens Tumors were weighed under sterile conditions, smeared on a sterile slide, washed twice in separate bijoux of sterile peptone water, and homogenized in sterile saline with a pestle and mortar. Gram stain of the smear was made to search for bacteria• Aliquots of 0.3 mL were taken from both washings, from neat homogenate and from homogenate diluted by a factor of 1:100; 0.1 mL quantities of each aliquot were inoculated onto two blood agar plates (one incubated aerobically in 10 % CO2 and the other anaerobically) and onto a McConkey agar plate. The number of bacterial colonies per plate was estiTABLEII. Organism Escherichia coli Citrobacter diversus Streptococcus fecalis S• agalactiae S. mitior S. milleri S. aeidominimus Staphylococcus epidermidis S. hemolyticus Peptostreptococcus spp Coryneforms Clostridium butyricum Rhodotorula minuta TOTALS

mated and therefore the number of bact:eria per; gram of tumor could be calculated. Samples o!iI neat homogenate were also inocul~:ed intdl Robertson cooked meat broth and (iolumbigl broth for enrichment; subcultures wele taken! after one day and after five days; these wereii inoculated onto blood agar plates as above (for~ subcultures from Robertson cooked meat) orI onto Columbia agar (for Columbia broth). All plates were incubated at 37 o C for at leasti five days before being discarded.

Processing oJ urine and blood cultures Volumes of 0.1 mL of each urine specimen were diluted in peptone water by a 2actor o~ 1:1000, then spread onto blood agar and Mc;I Conkey agar, and incubated in 10% CO~ fo~, forty-eight hours. Significant bacteriuria was defined as > 10~i) organisms mL -1. Blood samples were inocula;} ted into thioglycollate broth, glucose broth, and~i liquoid broth The broths were subcultureS:~ onto blood agar after two days and after five days; these were then incubated aerobically (ini •

Isolates.from tumors* Men Women Organisms/Gram of Tumor 0 5 (1) 104-10e 0 1 103 1 (1) 3 (1) 103-109 0 1 103 0 1 (1) l0 s 0 1 (1) 10s 0 1 (1) 109 1 0 103 0 1 103 5 2 103-105 0 2 102-104 0 1 103 0 1 103 7

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*Figures in brackets refer to the number of isolates from blood. One tumor grew 2 organisms in a male; 8 tumors grew > 2 Organisms in females.

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VOLUME XXXV, NUMBEBD

Microbiological summary )ata

Males

l)

35

:ia s

Females 16

4 10p < 0.05 7 12 p < 0.01 1 4 p < 0.05

tria a antibiotics:

0

0

10

12

2 1

7 p < 0.01 4 p < 0.05

anaerobically for five days berded.

f bacterial isolates ~tes were identified by standard :h API identification kits as appeptostreptococci and eorynet be satisfactorily identified to rs/s red test was used for statistical Results c distribution of bladder tumors nale and female patients (Table o correlation between tumor in:ology in either sex group.

9logy ~e of micro-organisms was isoe bladder tumors (Table II). n-positive cocci were not assoaificant bacteriuria or other in;ations. In 10 patients the ortg the tumor was a coliform or p, and the same organism was

isolated in significant numbers from the preoperative urine specimen in each case. In 4 of the 14 patients (29 % ) with significant preoperative baeteriuria postoperative clinical infections developed requiring parenteral antibiotics (Table III). Only 1 patient of the 37 (3 %) with sterile preoperative urine required parenteral postoperative antibiotics. W h e n those with sterile urine preoperatively were separately analyzed (Table IV), these numbered 37 (31 males and 6 females). Though 9/37 (24 % ) had positive tumor cultures and 9/ 37 (24%) had development of postoperative baeteriuria only 219 (22%) were from those with positive tumor cultures. Again there was no relationship between positive tumor culture and histologie grade or stage of tumor.

Comparison between males and females Seven males of thirty-five (20 % ) had infected turn ors (Table III), but four tumors grew only peptostreptoeoeei. T h e r e were twelve firstdiagnosed tumors, of which three (25 %) were infected. In 10 male patients significant postoperative baeteriuria developed, but all 10 had been catheterized at operation. Twelve of sixteen females (75 % ) had infected tumors, significantly more than in males (lO < 0.01). Ten (63 % ) had preoperative baeteriuria; the same organism in the urine was grown from the tumor in all eases. There were seven firstdiagnosed tumors, of which six were infected. Four females (25 % ) required parenteral antibioties for postoperative complications (3 with clinical evidence of septicemia). There was no correlation in either sex between first-diagnosed tumor and tumor infection, but there was a strong correlation between first-diagnosed tumors from females and the isolation of streptococci from the tumor (p < 0.01) and from the perioperative blood sample (p < 0.05). Bacteremia at operation was more frequent in females than in males (1 male in 35 [3% ] c o m p a r e d w i t h 4 females in 16 [ 2 5 % ] ) ,

TABLE IV. Patientswith negative preoperative urine culture Positive Positive Tumor --Blood Cultures-Positive Postop Sex No. Culture Periop Postop Urine Culture* dale 31 7 0 ,0 7 (2) ~emale 6 2 0 0 2 (0) ?oral 37 9 0 0 9 (2) *Figures in brackets are those with positive t u m o r cultures.

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(p < 0.05). There was a significant difference between males and females in the frequency that parenteral antibiotics were given (p < 0.05), and in the number of antibiotic courses initiated in hospital (p < 0.01) (Table III).

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Comment

This study found no relationship between tumor histology and infection, but overall identified a much higher incidence of tumor infection in females (75 % ) than in males (18 % ); if those with positive preoperative urine cultures are excluded, there was no difference. Serious infeefive complications requiring parenteral antibiotics were frequent in females (25 % ) but rare in males (3%). When female patients underwent TURBT for the first time, streptococci were frequently isolated from the perioperative blood sample. Streptococcal endoearditis is a well-recognized complication of urologic manipulations,5 and 3 percent of eases of endoearditis from a recent survey were linked to urologic surgery. 6 All patients with preoperative baeteriuria have been specifically excluded from previous studies. However, in clinical practice, the result of the preoperative urine culture is not always known at the time of surgery, and we considered tha~: it was important to include patients with unknown preoperative baeteriuria in our analysis. We found that when streptococci or eoliforms were isolated from tumors, they were always present in significant numbers in the preoperative urine specimen. As 57 percent of patients with significant preoperative bacteriuria required postoperative antibiotics (compared with 3 % with sterile urine before operation), exclusion of these patients would have led us to conclude, like previous authors, ~ that tumor infection and postoperative complications are uncommon. An unexpected finding was the variety of unusual organisms isolated, particularly from tumors in females; strict sterile technique was observed and large numbers of each isolate were found: evidence that these organisms were unlikely to be contaminants. Organisms such as eoryneforms (nonsporing gram-positive rods), which were isolated from 2 females, are thought to be of little pathogenic significance (so little that these organisms were not identifiable by a specialist laboratory); perhaps these organisms should be considered more as commensals and colonizers than "infecting" organisms.

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The isolation of these organisms, and a v a - / riety of alpha-hemolytic streptococci rarely iso-i lated from the urine, supports the contention ofi Appel e t al. ~ that the "bladder defense mecha, nism" can be disrupted by the presence of thel/ bladder tumor. Pathogens as well as e o m r n e n - i / sals can colonize the bladder tumor, which c a n l / then act as a focus for more serious i n f e c t i o n s . ' i The shortness of the female urethra presumably permits organisms to enter more frequently than in the male. Peptostreptococci were isolated as frequently I in males as in females. Investigations linked to I this study found peptostreptococci in the pc- i rioperative blood samples of males undergoing l transurethral resection of the prostate and opti' i eal urethrotorny for urethral stricture. It is pos-I sible that peptostreptoeocei are regular i n h a b i t : l ants of the abnormal urinary tract. We conclude t h a t females undergoing i TURBT are at particular risk of postoperativell infective complications. If the preoperativei urine is not known to be sterile, it would be a d . ~ visable for women to be given a prophylacti6I antibiotic active against streptococci and col~I iforms (amoxicillin would be a r e a s o n a b l ~ choice) • These data give little justification for~l the routine use of prophylactic antibiotics i 6 ~ otherwise normal males undergoing TURBT. !

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The London Hospital (Whiteehapel I London E1 1BB, Englani ! (MR. BADENOCH! ACKNOWLEDCMENTS.To ProfessorJ. 1). Blandyand M:

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A. M. I. Paris for allowing us to include their patients i~! this study; to Professor J. D. Williams, Professor M, Casewell, and Dr. T. Healing for their critical advice; an ~ especially to the staff of Brooks and Alexandra wards t ~ the London Hospital, Mile End.

References

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1. Appel RA, Flynn JT, Paris AMI, and Blandy JP: Occult b a c J terial colonization of bladder tumors, J Urol 124:345 (1980)i 2. Goldwasser B, eta[: Urinary infection following transur ~! ~ thral resection of bladder tumors~rate and source, J Urol i ~ 1123 (1983). 3. UICC (International Union against Cancer): TMM Glassff~ cation of Malignant Tumours 3rd edition, MH Hammer, G e n e ~ UICC, 1978. 4. Cowan ST: Manual for the Identification of Medical B a c 4 ria: 2nd ed, Cambridge University Press, 1974. 5. Siroky MB, M0ylan RA, Austen G, and Olsson CA: M . static infection secondary to gemtomrmary tract sepsis, Am J .Me~:~ 61:351 (1976). 6. Skehan JD, Murray M, and Mills PG: Infective endoca~r~]l ditis: current incidence and mortality. Abst Proc Br Cardiac So November 26, 1985, Br Heart J, 54:614 (1985).

UROLOGY / JANUARY1990 / VOLUME XXXV,

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Microbiological study of bladder tumors, their histology and infective complications.

The microbiology of bladder tumors and the infective complications of transurethral resection (TURBT) were studied prospectively in 51 patients. Patie...
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