International Journal of Antimicrobial Agents 23S1 (2004) S17–S23

Controversies in antibiotic prophylaxis in urology

Magnus Grabe
Department of Urology, Malmö University Hospital, Malmö, SE-205 02 Sweden

Abstract

Antibiotic prophylaxis in urologic surgery remains controversial. However, progress has been made and some of the controversies have
been answered. Firstly, it is important to underline that urologic diagnostic and therapeutic procedures can induce surgical site infections
(SSIs), bacteriuria, pyelonephritis and septicaemia in a substantial number of patients, too great to be neglected. Secondly, as patients are
different and have various risk factors, a careful assessment of the patient and its individual risk is crucial. Thirdly, the same procedure may
be totally different from one individual to another and they can rarely be grouped as standard procedures. A floating level of invasiveness
is followed by a variation of the risk of infection. Fourthly, the pathogens and their susceptibility pattern vary extensively in Europe so that
no clear-cut recommendations as for the choice of antibiotics can be given. Basic principles of antibiotic prophylaxis in terms of timing,
mode of administration and length of regiment apply for urologic interventions. Thus, clean operations will usually not require antimicrobial
prophylaxis except for those including the implant of a prosthetic device, while clean-contaminated will benefit from preventive antimicrobials.
It is the task of the urologists to carefully assess each individual patient and procedure to opt for an optimal prophylaxis.
© 2003 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Keywords: Antibiotic prophylaxis; Urologic surgery

1. Introduction ated infection in patients defined as free from infection at

Antibiotic prophylaxis has been controversial in urologic
surgery for decades. When searching in PubMed, only a
limited number of publications on the subject are found
for most urologic procedures, especially in the last decade.
The best-studied interventions are transurethral resection of
the prostate (TURP) and transrectal ultrasound guided core
biopsy of the prostate. Urologic diagnostic and therapeutic
procedures have in recent years rapidly developed, reduc-
ing the value of older studies for evidence assessment. The
remarkable changes have gone faster than the possibility
to keep updated with a sufficient number of well-designed,
randomised controlled studies. Also, the comparability
between different studies is difficult due to different defi-
nitions, study design and quality [1]. These difficulties are
the fundaments of the controversies regarding the use of
antibiotics as prophylaxis in urologic surgery.
This paper reviews some aspects of the present controver-
sies related to the prophylactic use of antimicrobial agents
in urologic diagnostic and therapeutic procedures. Antimi-
crobial agents are used for prophylaxis as one of several
measures to prevent the emergence of a health care associ-
E-mail address: magnus.grabe@skane.se (M. Grabe).
the time of intervention. It includes patients undergoing a
clean-contaminated procedure.
2. Risk of infection
The first question to be answered is whether there is ev-
idence for infectious complications in association with uro-
logic procedures. The answer is yes. This was recognised for
more than 120 years and elegantly described by Sir Andrew
Clark in The Lancet in 1883, reporting on the association
between catheterisation and fever, called catheter fever [2].
Health care associated infections are summarised in
Table 1. What urologist mostly fear, are deep surgical site
infections (SSIs), complicated urinary tract infections (UTI),
pyelonephritis and septicaemia, all of which represent a
threat for the patient at an increased cost to society.
Table 2 summarises the expected rates related to some
standard urologic procedures.
2.1. Diagnostic procedures
Ultrasound guided core biopsy of the prostate has become
one of the most frequent diagnostic tools in urology, aimed at

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doi:10.1016/j.ijantimicag.2003.09.005
S18 M. Grabe / International Journal of Antimicrobial Agents 23S1 (2004) S17–S23

Table 1 Ureteroscopy and percutaneous stone surgery is followed

Health care associated infections in urologic surgery by infectious complications in up to 25%. Such high rates
Surgical site infection (SSI) seem related to the level of difficulty of the procedure and
a. Superficial possibly to the fact that longer operations will be done under
b. Deep relatively high pressure within the urinary tract [6].
Urinary tract infection (UTI)
a. Asymptomatic bacteriuria
b. Symptomatic UTI 2.3. Open procedures
c. Complicated UTI or febrile upper UTI
d. Pyelonephritis Open urologic operations have not been studied as specif-
Blood stream infection—Septicaemia ically as frequent operations in general surgery. However,
Infection at a remote site
it is reasonable to assume that a similar pattern could be
expected. Operations have been divided into clean, clean
contaminated, contaminated and dirty-infected with an ex-
diagnosing early prostatic cancer. It is a quick, low-invasive pected risk of SSI of approximately 2, 8, 15 and 40%, re-
procedure, but associated with a fairly high risk of infection spectively [7,8]. In studies concerned with implantation of
[1,3], whereas cystoscopy, the other most frequent invasive urologic devices such as penile prosthesis and artificial uri-
diagnostic tool, leads rarely to an infectious complication nary sphincters, infectious rates range from 1 to 17% [9].
[4]. The environment is different. In the first, the medium As for urinary tract infection, they are associated with tran-
size needle passes through the rectal mucosa loaded with sitory treatment with an indwelling catheter.
its rich flora. In the second, the instrument slides along the
urethra after a disinfectant gel has been acting for a few
minutes. 3. Patients’ characteristics

2.2. Endourologic procedures
TURP, still one of the main transurethral operations, has
during the past two decades been the subject of a number of
controlled studies. In a meta-analysis of 32 studies, Berry
and Barret [5] found an average rate of bacteriuria and uri-
nary tract infection of 26% in 4260 patients and septicaemia
in 4.4%. Other transurethral interventions have not been
studied extensively and it is difficult to draw any conclusion
for transurethral resection of bladder tumour, for instance.
The patients’ characteristics and risks differ to a great ex-
tent. A good history and clinical examination will reveal the
patient’s general preoperative physical status and stratify
the risk according to the norms as defined for instance by
the American Society of Anaesthesiologists [10]. Then, the
patient has to be characterised as for his/her endogenous and
exogenous risk factors. General risk factors for infectious
complications are high age, poor nutritional status, diabetes
mellitus, smoking, extreme weight, coexisting infection
at a remote body site, colonisation with micro-organisms,

Table 2
Expected rate of infection in conjunction with urologic surgery, expressed in % (based mainly on reviews 5, 9, 13, 18, 30)
Procedure Infection rates (reported/expected)

No antibiotic prophylaxis With antibiotic prophylaxis

Bacteriuria/UTI Febrile/UTI Sepsis Rates of Febrile UTI/ sepsis

Diagnostic procedures
Core biopsy of the prostate 20–53 5–10 1–5 <5
Cystoscopy, urodynamic examination <20 <5 No data No impact
Ureteroscopy No data available (not differentiated from stone operations) No impact demonstrated
Endourologic procedures and ESWL
ESWL <5 <5 1 Minimal impact
TURP 6–70 5–10 <5 Reduction with 66–71%
Ureteroscopy—uncomplicated Not differentiated from complicated in available studies
Ureteroscopy (complicated) percutaneous <38 4–25 <5 Significant reduction expected
stone surgery
Open surgery UTI SSI Sepsis
Clean (nephrectomy) Catheter associated <2 No data No impact demonstrated
Clean-contaminated (open urinary tract; Catheter associated 5–10 <3 2–3%
bowel segment)
Implant of prosthetic devices Catheter associated 1–16 No data 1–3%
Laparoscopic procedures Catheter associated No data No data No data
No data indicates limited or no data available for that specific intervention.
 M. Grabe / International Journal of Antimicrobial Agents 23S1 (2004) S17–S23
usually after a long pre-operative hospital stay, altered im-
mune response and a lack of control of these risk factors [11].
The environment is of importance. Taking for granted
that all measures of sterility and preparation of the patient
are made properly, it is essential to further characterise the
host related environment and the pathogen load related to
the intervention. The presence of a urinary tract calculus,
of “hidden” bacteria or other potential source will highly
increase the risk of infection [12]. The conclusion of a re-
view on risk factors in urology draw the conclusion that our
present knowledge is not sufficient and that risk factor anal-
ysis has to be integrated in the design of forthcoming clinical
studies [9].
4. The procedure
The procedure is a key matter. All ‘same’ procedures are
not all the same. They are patient-related. It is possible to plot
the different urologic interventions in relation to the level
of invasiveness from the standard diagnostic low-invasive
procedures to the highly invasive open clean-contaminated
operations. However, the risk of infection is not directly cor-
related to the level of invasiveness. An empirical illustra-
tion is given in Fig. 1 [13]. For a similar instrumentation or
operation there is a floating level of invasiveness and risk
of infection. Obviously, an older man operated upon for a
large, bleeding prostate will be at a markedly higher risk of
infection that a healthy man undergoing the same procedure
for a smaller prostate. A single distal ureteral stone will be
a lesser problem than a proximal, impacted, obstructive one
[6]. What we do not know is why some patients will develop
an infectious complication while others will not. Nor do we
know much about bacterial virulence in urologic patients.
A source of controversy in urology is the relevance of the
“natural” bacterial load harboured in the urethra, vagina and
prostate. This load is of such an importance in the patients
suffering from a disease of the lower genitourinary tract
Fig. 1. Empirical relation between degree of invasiveness of routine urologic procedures and expected risk of infectious complications (modified from 13).
S19
that some authors consider the local environment as con-
taminated [14]. This is also probably true for endo-urologic
interventions such as percutaneous stone surgery and ad-
vanced ureteroscopic operations because the upper urinary
tract can harbour bacteria despite a “sterile” urine culture
[9]. An interesting discussion is whether operations involv-
ing the opening of the urinary tract are to be considered in
a similar way as those involving a bowel segment and, thus,
be classified as clean-contaminated procedures. It is likely,
although evidence based information is lacking, that so is
the case.
5. Reduction of infection rates by antibiotic
prophylaxis
The expected rates, rate reduction or expected impact of
antibiotic prophylaxis are summarised in Table 1.
5.1. Diagnostic procedures
Most recent studies show that antibiotic prophylaxis re-
duces the rate of infection in core biopsy of the prostate
[1,3], although some authors have questioned its need [15].
With antibiotic coverage, the rates seem to be less than five
per cent, usually around 2–4%. No impact of antibiotic pro-
phylaxis has been reported for cystoscopy, urodynamic ex-
aminations and diagnostic simple ureteroscopy.
5.2. Endourologic procedures
TURP is the best-studied urological intervention. Chodak
and Plaut [16] showed in 1978 that antibiotic prophylaxis
could not be recommended in TURP, as there was a lack
of scientific stringency in the available reports. Ten years
later, a review of the growing literature indicated that pa-
tients undergoing TURP would in most cases benefit from
a short course of antibiotics [17]. The recent meta-analysis
S20 M. Grabe / International Journal of Antimicrobial Agents 23S1 (2004) S17–S23
could show that there was sufficient evidence for antibiotic
prophylaxis in TURP. A single dose and a short course
(<72 h) reduced the infection rate by 66 and 71%, respec-
tively. The use of an antimicrobial as a prophylactic inten-
tion was expected to protect 175 out of 1000 patients from
bacteriuria and between 9 and 20 patients from septicaemia,
which must be considered as an important winning in terms
of human suffering and cost.
5.3. Open procedures
The rate of infection in clean operations such as standard
nephrectomy, when the urinary tract is not opened, is low
(Table 2). The topic has been very little evaluated in con-
trolled studies and there is presently no evidence for any
impact of antimicrobial prophylaxis. However, antibiotic
prophylaxis is recommended in clean operations when in-
cluding the implantation of prosthetic device [18]. A deep
infection around the prosthesis usually requires its removal,
at high cost for the patient and the health care system. With
antibiotic prophylaxis, this rate is reduced to a few per cent
[9,19].
Surgical antimicrobial prophylaxis has been shown in
many randomised clinical trials to reduce the incidence of
postoperative wound infections in clean-contaminated op-
erations. A reduction from some 5–10% or more to <2–3%
is expected [18,20,21]. Retropubic total prostatectomy,
nowadays one of the most frequent urologic operation in
the western world, has to our knowledge, not been studied
in controlled studies. However, as the lower urinary tract
is opened, the procedure should probably be classified as
clean-contaminated.
5.4. Contaminated and dirty procedures
In contaminated and dirty operations antimicrobial agents
are given with a therapeutic intention. Infected urine is a
very high risk factor for both SSI in for instance open prosta-
tectomy [22] and febrile UTI after TURP [23]. Patients with
indwelling catheter, nephrostomy tube or other stent device
should be considered as having bacteriuria and should be
treated in advance (between 3 and 7 days prior to operation)
in order for the urine to be sterile at the time of surgery.
The patient should be covered well beyond the intervention
(usually for some 7–10 days or longer) depending on the
type of the operation and the underlying condition.
6. Choice of antibiotics
No clear-cut recommendations can be issued, as there are
great variations in Europe regarding bacterial distribution
and, especially, bacterial susceptibility to different antibi-
otics. The antimicrobial resistance is usually higher in the
Mediterranean countries as compared with the northern Eu-
ropean countries and correlated to the four-fold difference
in consumption of antibiotics. For instance, ampicillin resis-
tance in Spain and Portugal are reported to be 54 and 45%,
respectively, as compared with 16% in Sweden. Quinolone
resistance is reported at greater than 20% in several southern
European countries but only a few percent in the northern
ones [24]. Local knowledge about the pathogens’ profile and
susceptibility pattern is, consequently, of paramount impor-
tance in setting up a rational antibiotic policy. It also stresses
the need of control in the use of antimicrobial agents.
Pathogens will vary with the procedure. Gram-negative
strains will be the most frequent in endoscopic procedures
and clean contaminated operations, while Gram-positive
strains, mainly Staphylococcus spp, dominate in wound
infections in prosthetic implant surgery.
In choosing an antimicrobial agent, one has to consider
the contamination load, the target organ and potential risk
of infection, the pressure established within the urinary tract
at operation (endoscopic procedures) and the role of local
inflammation.
7. Timing
There is a given time frame during which antibiotic pro-
phylaxis should be administered. Burke showed in 1961
that there was a defined period of 3 h when the developing
staphylococcal dermal or incisional infection could be sup-
pressed by antibiotics [25]. In clean-contaminated surgical
procedures, optimal time appears to be up to 2 h before but
not later than 3 h after the start of an intervention [26]. The
urinary tract may be different but has not been extensively
studied. In experimental studies in rats, it was shown that
the antibiotic should be administered before intervention but
not later than 6 h after the procedure to prevent UTI [27].
The rational for this is to reach a peak concentration at
the time of highest risk during the procedure and an ac-
tive concentration present during the time of operation. It is
worth noting that the time to development of a blood stream
infection could be rather short, <1 h.
8. Length of regimen
8.1. Diagnostic procedures
The length of regimens for core biopsy of the prostate still
required to be elucidated. Long-term quality control regis-
tration comparing different antibiotics and regimens and risk
factors as that has been set up in our setting, is a possible
way to answer the matter [28].
8.2. Endourologic procedures
The length of regimen in endourologic procedures has
not been well studied for most procedures. Only in TURP,
it has been shown that a medium short regimen of <72 h is
superior to a single dose, observing an infection reduction
 M. Grabe / International Journal of Antimicrobial Agents 23S1 (2004) S17–S23 S21

rate of 71% as compared with 66% [5]. No recommendations
prevail for other standard transurethral instrumentations.
8.3. Open procedures
For open, clean-contaminated operations, the length of
the procedure has been defined as a risk factor for infec-
tion as have the operative technique, the surgical skill, and
the preoperative preparation of the patient and the skin [26].
Thus, prolonged, difficult operation could require repeated
dosages to maintain a sufficient level of circulating antibi-
otic during the procedure and immediate postoperative risk
period. It seems reasonable to transfer this experience to uro-
logic clean-contaminated procedures that include bowel seg-
ments. However, it is less known whether this opinion could
be transposed to open or laparoscopic procedures when the
urinary tract is opened. It could only be presumed to be so.
9. Principles of antibiotic prophylaxis
The basic principle is to protect the patient against serious
adverse infectious complications associated with urologic
diagnostic and therapeutic interventions and reduces costs
for the health care sector. This also means keeping the total
consumption of antimicrobial agents in the urologic wards
at the lowest reasonable level and avoiding stretching the
microbial environment.
The present review illustrates the importance of individu-
alising the antibiotic prophylaxis and that the antimicrobial
agent has to be given within a given timeframe. It should be
as short as possible, respecting, however, the operation re-
lated risk events. The microbial profile is regional and even
local and has to be known. The antibiotic should cover the
expected pathogen profile and the pharmacological proper-
ties in respect to the target organ.
Almost all antimicrobial agents could be used for pro-
phylaxis. Oral administration is as good in most clinical
situation, such as core biopsy of the prostate, transurethral
resection of the prostate and standard ureteroscopy, while
intravenous administration is recommended for long-lasting
operations involving the bowel (reconstructive surgery),
complicated endourologic interventions and patients at high
risk.
It is advisable to use different drugs for prophylaxis and
therapy, and reserve the ‘powerful’ antibiotics for therapy.

Table 3
Approach to antibiotic prophylaxis in urologic surgery (modified from 29 to 30)
Procedure Pathogens (expected) Antibiotic prophylaxis Remarks

Diagnostic procedures
Transrectal biopsy of the prostate Enterobacteriaceae All patients Short course,
Anaerobes? Length to be determined
Cystoscopy Enterobacteriaceae No Consider in risk patients
Urodynamic examination Enterococci
Staphylococcus spp.
Ureteroscopy Enterobacteriaceae No Consider in risk patients
Enterococci
Staphylococcus spp.
Endourologic surgery and ESWL
ESWL Enterobacteriaceae No In patients with stent or nephrostomy tube
Enterococci
Ureteroscopy for uncomplicated stone Enterobacteriaceae No Consider in risk patients
Enterococci In patients with stent or nephrostomy tube
Staphylococcus spp.

Ureteroscopy of proximal or Enterobacteriaceae All patients Short course

impacted stone and PCNL Enterococci Length to be determined
Staphylococcus spp Intravenous suggested
Open urologic surgery
Clean operations Skin pathogens No Consider in high-risk patients.
Catheter associated Short catheter treatment
Clean-contaminated Enterobacteriaceae Suggested Single peri-operative course
Open urinary tract Enterococci
Clean-contaminated Enterobacteriaceae All patients As for colonic surgery
Bowel segments Enterococci
Anaerobes
Skin bacteria
Implant of prosthetic devices Staphylococci All patients
Skin bacteria
Laparoscopic procedures Skin bacteria? Se remarks As for open surgery
S22 M. Grabe / International Journal of Antimicrobial Agents 23S1 (2004) S17–S23
The drugs should cover most expected procedure-related
pathogens, keeping the local susceptibility pattern in mind.
It is also reasonable to use different drugs to reduce the
ecological pressure. The regimen’s length should be kept
as short as possible and, regrettably, we still have too little
evidence-based information about rational length of antibi-
otic prophylactic regimens for most urological procedures
10. EAU recommendations
It is important to keep in mind that the use of antibi-
otics in urologic surgery is only one of several measures
aimed at preventing the emergence of health care associ-
ated infections. A working group or the European Society
of Infection in Urology (ESIU), a member of the Euro-
pean Association of Urology (EAU), has developed guide-
lines for the treatment of genitourinary infections and prac-
tical antibiotic prophylaxis to support European urologist
[29,30].
As a baseline, urologic operations follow the same
principles as general surgery. Clean operations—patients
considered as “free” from bacterial contamination at the
time of intervention, do usually not require antibiotic pro-
phylaxis, with the exception of implant of a prosthetic
device. On the other hand, clean-contaminated procedures,
i.e. operations involving the opening of the urinary tract
and/or the bowel, should be given antibiotics as a pro-
phylactic intention. Contaminated and dirty operations
are given antimicrobial agents as a therapeutic intention.
The recommendations are presented in a modified form in
Table 3.
Patients with indwelling catheter, nephrostomy tube or
other stent device should be considered as having bacteriuria
and treated as mentioned above.
11. Conclusions
In summary, there is no doubt that urologic procedures are
associated with infectious complications ranging from sim-
ple bacteriuria to life threatening septicaemia. This is linked
to the host and its potential risk factors, the environment and
the procedure. The longer and more complicated the proce-
dure, the great the risk. However, even simple, frequent di-
agnostic procedures such as ultrasound guided core biopsy
of the prostate are associated with a greater risk of septi-
caemia than highly invasive procedures such as nephrectomy
and laparoscopic total prostatectomy. Moreover, it has been
shown for several types of interventions that the patients will
benefit from antibiotic prophylaxis given peri-operatively
and covering the period at risk. Therefore, a cautious eval-
uation of the patient, risk factors, environment and type
of intervention is of major importance to ensure a safe
procedure considering also the ecology, local strategy and
costs.
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