Original Article
CIPROFLOXACIN BEFORE PCNL FOR UPPER UTI AND UROSEPSIS
MARIAPPAN
et al.
Urosepsis after percutaneous
nephrolithotomy (PCNL) is a severe
complication, and its avoidance
can sometimes be difficult despite
antibiotic prophylaxis. Authors
from the UK with a considerable
experience in this procedure
describe a prospective controlled
study using ciprofloxacin for 1
week before PCNL, and found that
it significantly reduces the risk of
urosepsis.
© 2006 THE AUTHORS
JOURNAL COMPILATION
One week of ciprofloxacin before
percutaneous nephrolithotomy
significantly reduces upper tract
infection and urosepsis: a prospective
controlled study
Paramananthan Mariappan, Gordon Smith, Sami A. Moussa and
David A. Tolley
Western General Hospital, Urology, Edinburgh, UK
Accepted for publication 12 June 2006
OBJECTIVE
To evaluate whether 1 week of ciprofloxacin
before percutaneous nephrolithotomy (PCNL)
in patients with stones of ≥ 20 mm or
pelvicalyceal dilatation, reduces urosepsis, as
we previously reported that such patients
have four times the risk of urosepsis after
PCNL.
PATIENTS AND METHODS
Patients undergoing PCNL, and who fulfilled
strict selection criteria, were recruited
prospectively into a study which was
conducted in two phases. The study methods
were similar to those previously described;
patients with dilated pelvicalyceal systems
and/or stones of ≥20 mm from phase 1
(previously published) acted as controls. In the
subsequent phase, the same selection criteria
applied and only those with stones of
≥20 mm and/or dilated pelvicalyceal systems
were given ciprofloxacin 250 mg twice daily
for 1 week before PCNL and comprised the
treatment arm. Midstream urine samples,
renal pelvic urine and fragmented stones
were collected to assess culture and
sensitivity. Systemic inflammatory response
syndrome (SIRS) was used to define urosepsis
after PCNL. The urologists monitoring the
© 2 0 0 6 B J U I N T E R N A T I O N A L | 9 8 , 1 0 7 5 – 1 0 7 9 | doi:10.1111/j.1464-410X.2006.06450.x
patients after PCNL and conducting the
analysis were all unaware of the
characteristics of the stones or intravenous
urography findings before PCNL. In all, 115
patients (54 in phase 1 and 61 in phase 2)
were recruited, of whom 46 in phase 1 and 52
in phase 2 had stones of ≥20 mm and/or a
dilated pelvicalyceal system, and became the
control and treatment arms, respectively.
RESULTS
The patient demographics were similar in
both arms. There was three times less risk of
upper tract infection (relative risk 3.4, 95%
confidence interval 1.0–11.8, P = 0.04) and
SIRS (2.9, 1.3–6.3, P = 0.004) in the patients
receiving ciprofloxacin (treatment arm).
CONCLUSIONS
The administration of oral ciprofloxacin for
1 week before PCNL in patients with stones of
≥20 mm or dilated pelvicalyceal systems
significantly reduced the risk of urosepsis.
KEYWORDS
percutaneous nephrolithotomy, controlled
study, urosepsis, urine culture and sensitivity,
systemic inflammatory response syndrome
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M A R I A P PA N ET AL.

INTRODUCTION FIG. 1. Flow chart of patient recruitment into either arm of the current analysis. Data collection from phase
2 is ongoing and forms part of a separate analysis.
Urosepsis is a potentially catastrophic
complication that can follow percutaneous PHASE 1
nephrolithotomy (PCNL) despite sterile (Commenced: June 2003)
preoperative urine and prophylactic
antibiotics [1,2]. O’Keeffe et al. [1] reviewed
retrospectively a series of 700 patients
EXCLUSION CRITERIA
undergoing upper tract manipulation; nine
(Appendix 1)
developed severe septicaemia and 66% died.
The source of this systemic infection has
often been attributed to infection in the upper
tracts, although preoperative mid-stream N = 54 PHASE 2
(Analysis completed and (Commenced June 2004)
urine (MSU) samples were sterile. We showed
submitted in May 2004)
in a previous report [3] that infection in the
upper tracts (either renal pelvic urine or
stones) had four times the risk of resulting in
urosepsis after PCNL. That study showed EXCLUSION CRITERIA
simultaneously that patients with larger Subgroup with non-dilated (Appendix 1)
stones (≥20 mm) or dilated pelvicalyceal pelvicalyceal systems and/
systems had a significantly greater risk of or stones <20mm
N=8 N = 61
infected upper tracts. Therefore, as a natural
continuation of this study, we further
evaluated if a 1-week course of ciprofloxacin
in patients with a dilated pelvicalyceal system
Subgroup with Dilated
or stones of ≥20 mm could reduce the risk of pelvicalyceal systems and/
upper tract infection or urosepsis, thus Subgroup with Dilated or stones ≥20mm
completing the audit loop. pelvicalyceal systems and/ (TREATMENT ARM –
or stones ≥20mm given Ciprofloxacin prior
(CONTROL ARM) to PCNL)
PATIENTS AND METHODS N = 46 N = 52

As a part of a series of ongoing investigations Subgroup with non-dilated

on sepsis and stone surgery, we prospectively
collected data on all patients undergoing
PCNL at our centre from June 2003. All
patients included had sterile MSU samples
before PCNL, as checked 1 week before
surgery. Appendix 1 lists the study exclusion
criteria, which excluded patients with
confounding factors that would have
predisposed to urosepsis/UTI. Summarising
the previously reported methods [3]; all
patients received i.v. gentamicin 5 mg/kg body
weight at the time of induction for the PCNL.
Samples collected for culture and sensitivity
(C&S) were MSU, pelvic urine and fragmented
stones as per our previous description [3].
Each patient was left with a nephrostomy
tube for 24 h before it was clamped and
removed. Sepsis, fever and pain after
nephrostomy clamping led to a further period
of free drainage. Patients were monitored
after PCNL for signs of systemic inflammatory
response syndrome (SIRS) (as defined in
Appendix 2); other overt causes (e.g. pain,
deep vein thrombosis and pneumonia) were
excluded before attributing the SIRS to the
urinary tract.
CURRENT ANALYSIS
of prospectively recruited
treatment vs control arms
The first phase of the series, with 54 patients,
was reported previously [3] and we continued
to prospectively collect similar data from
patients undergoing PCNL with the same
selection criteria (phase 2). Because we found
in phase 1 that patients with dilated
pelvicalyceal systems and/or stones of
≥20 mm were at greater risk of upper tract
infection, which in turn predicted urosepsis,
we instituted a local protocol to give all
patients with dilated pelvicalyceal systems
and/or stones of ≥20 mm a 1-week course of
ciprofloxacin before PCNL. This present study
was designed to compare the risk of upper UTI
and urosepsis between those receiving
ciprofloxacin (treatment arm) and a similar
subset with dilated pelvicalyceal systems and
stones of ≥20 mm in the historical cohort
(control arm) from the previous report. Figure
1 shows the recruitment of patients.
pelvicalyceal systems and/
or stones <20mm
N=9
The presence of dilated pelvicalyceal systems
and stones of ≥20 mm were determined from
the IVU before PCNL by one uro-radiologist
(S.A.M.) who was unaware of the subsequent
observations and specimen culture results.
The urologists monitoring the patients after
PCNL and conducting the analysis were all
unaware of the IVU/stone characteristics
before PCNL. Urosepsis in this study was
defined as SIRS or shock in the absence of
other potential sources. Blood was cultured
from patients who developed SIRS.
The results were analysed statistically using
Fisher’s exact and the Mantel-Haenszel chi-
square tests to determine associations
between the various groups and subgroups.
The t-test was used to compare mean stone
size between the groups analysed. Univariate
analysis was used to determine any

© 2006 THE AUTHORS

107 6 JOURNAL COMPILATION © 2006 BJU INTERNATIONAL
 CIPROFLOXACIN BEFORE PCNL FOR UPPER UTI AND UROSEPSIS

association between SIRS and other variables.

TABLE 1 Patient and stone demographics in both phases of the study. There was no statistically
The type 1 error was set at 0.05.
significant difference between them

Variable Phase I Phase II

RESULTS
Number of patients 54 61
Male: female 28 : 26 35 : 26
In all, 115 (54 in phase 1 and 61 in phase 2)
Mean (range):
patients were recruited, based on the
Age, years 53.1 (24–83) 55.5 (27–84)
selection criteria. Table 1 lists the patient and
Stone size, mm 32.8 (15–80) 30.8 (4–100)
stone demographics. Six patients (three in
Duration of surgery, min 70.7 (30–180) 54.5 (20–120)
each phase) required two percutaneous tracks
N:
to achieve complete stone clearance. None of
Easy puncture 41 45
the patients required blood transfusion or
Turbid urine on puncture 6 5
developed hypovolaemia from blood loss.
Previous documented UTI 15 17
There were 46 patients in the control arm and
Residual stones 17 15
52 in the treatment arm (Fig. 1). Figure 2
Stones ≥20 mm alone 46 48
describes the MSU, pelvic urine and stone
Dilated pelvicalyceal system alone 24 22
culture results in the control and treatment
Stones ≥ 20 mm and/or dilated pelvicalyceal system 46 (control) 52 (treatment)
arms. The use of ciprofloxacin significantly
reduced the incidence of upper UTI (i.e. pelvic
urine and stones) in the treatment arm; the
FIG. 2. Comparison of the culture results in patients with stones of ≥ 20 mm or dilated pelvicalyceal systems incidence of infected pelvic urine was three
in the control and treatment arms. times less (relative risk, RR, 3.4, 95% CI 1.0–
11.8, P = 0.04) and the risk in the incidence of
100 infected stones was halved (2.3, 1.1–4.5,
P = 0.016).
80
Percentage of patients

28 In the treatment arm, the risk of SIRS was

60 37 43 three times less (RR 2.9, 95% CI 1.3–6.3,
41 46 49
P = 0.004; Fig. 3). Of the seven patients in the
40 treatment arm with SIRS, four had infected
stones and one infected pelvic urine. Two of
20 18 these patients, both with infected stones,
9 9 developed septic shock. A subgroup analysis
5 6 3
0 of the patients with only dilated pelvicalyceal
MSU C & S MSU C & S PELVIC C & S PELVIC C & S STONE C & S STONE C & S systems showed that 10 of 24 (42%) in the
(control) (treatment) (control) (treatment) (control) (treatment) control arm developed SIRS, whereas only one
of 22 (5%) in the treatment arm developed
, , = positive; = negative.
SIRS (RR 9.2, 95% CI 1.3–65.9, P = 0.004).

Figure 4 shows the relationship between

FIG. 3. Risk of SIRS in the control and treatment arms (RR 2.9, 95% CI 1.3–6.3, P = 0.004). stone size, stone infection and SIRS, whereby
larger stones appear more likely to be
100
infected, especially in those who developed
SIRS. From the pooled t-test, the mean size of
80 infected stones (29.8 mm) was significantly
Percentage of patients

28
smaller than the uninfected stones (37.6 mm;
P = 0.04). This relationship was maintained in
60
45 both phases of the study.

40
DISCUSSION
20 18
Most centres worldwide use antibiotic
7 prophylaxis in accordance with the Infectious
0 Diseases Society of America and European
Control Treatment (ciprofloxacin) Society of Clinical Microbiology and
Infectious Diseases guidelines [6], but the
SIRS; No SIRS empirical prescription of preoperative

© 2006 THE AUTHORS

JOURNAL COMPILATION © 2006 BJU INTERNATIONAL 107 7
M A R I A P PA N ET AL.
antibiotics for longer is being used for
patients with a ‘higher risk’ of urosepsis. To
our knowledge this is the first controlled
study of its kind to show the benefits of this
extended period of antibiotic prophylaxis
before stone surgery. We showed that
infected pelvic urine, infected stones and
urosepsis can significantly be reduced with
1 week of oral ciprofloxacin in patients with
large stones and dilated pelvicalyceal systems,
who are at greater risk of urosepsis after
PCNL. The inability to reduce the infection
within stones in a few patients might be
attributed to the impenetrability of the
stones, presence of endotoxins in the stone
matrix [7] and the possibility that the patients
did not comply with the preoperative
antibiotic regimen.
Despite careful preparation before PCNL,
patients still develop systemic and sometimes
catastrophic infection. Urosepsis and shock
occur in direct proportion to the duration of
the procedure, bacterial load in the urine,
severity of obstruction by the stone and
presence of infection in the stone [8]. MSU
samples have been shown not to represent
the infection present in the upper tracts
[3,4,9–11]. Conversely, stone and pelvic urine
C&S were better predictors of urosepsis after
surgery and large stones appeared more likely
to be infected. Shigeta et al. [12] found
infected stones in 10% of their 57 patients
with renal stones, and found that bacteriuria
was more prevalent in stones of >30 mm in
diameter. However, Gault et al. [13] attributed
the lower risk of infected stones in their series
(5.6%) to a longer period of preoperative
antibiotics, using fluoroquinolones. Our
rationale for using ciprofloxacin was guided
by discussion with microbiologists, based on
local sensitivity patterns. A recent surveillance
study [5] showed that ciprofloxacin was
highly effective for treating uropathogens,
with susceptibility rates for Escherichia coli,
Klebsiella pneumonia, Pseudomonas
aeruginosa and Proteus mirabilis being 98%,
94%, 89% and 87%, respectively.
We used SIRS to define urosepsis, as it is a
reliable, objective and convenient clinical
marker. Septic shock would have been a more
conclusive measure, but its rarity [14]
precludes meaningful results with a moderate
sample.
Stone or pelvic urine cultures are available
only after surgery but appear to be the best
guide for antibiotic therapy in case of sepsis.
107 8
FIG. 4. Relationship between stone bulk (in mm), stone C&S and SIRS in both phases.
1 2
100.00
80.00
60.00
Stone bulk
40.00
20.00
0.00
negative
SIRS absent present
However, using stone bulk and pelvicalyceal
dilatation as suitable surrogate markers [3] for
upper UTI, ciprofloxacin for 7 days before
PCNL reduced the risk of sepsis afterward, and
the potentially longer course of antibiotics
needed for therapeutic antibiotics, as well as
reducing the duration of stay in patients who
would otherwise develop sepsis.
In conclusion, the present results suggest
that treating patients who have dilated
pelvicalyceal systems and/or stones of
≥20 mm before PCNL with ciprofloxacin
250 mg twice daily for 1 week significantly
reduces the risk of upper UTI and urosepsis.
Although our findings provide evidence to
corroborate most urologists’ practice, a
multicentre randomized controlled trial
should be done to further confirm these
results.
ACKNOWLEDGEMENTS
We thank Mr Ammar Alhasso, Mr Simon V.
Bariol, Mr Eng Ong, Mr Richard Pamberton
and Mr Asif Raza for completing the study
proformas. Special thanks also to the staff of
the Endourology Theatre of the Western
General Hospital for diligently collecting
specimens for analysis.
Study phase
positive negative positive
Stone C&S
CONFLICT OF INTEREST
None declared.
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CIPROFLOXACIN BEFORE PCNL FOR UPPER UTI AND UROSEPSIS
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Correspondence: Paramananthan Mariappan,
Western General Hospital, Urology, Edinburgh,
UK.
e-mail: param.mariappan@nhs.net
Abbreviations: PCNL, percutaneous
nephrolithotomy; MSU, midstream urine;
C&S, culture and sensitivity; SIRS, systemic
inflammatory response syndrome; RR, relative
risk.
Exclusion criteria
1. Patients with a stent, nephrostomy tube or
indwelling catheter
2. Diabetes mellitus
3. Renal failure
4. Fever before surgery
5. Previous manipulation/procedure
6. Concomitant bladder stone or tumour
7. Patients with active UTI
8. Contralateral renal/ureteric stone
APPENDIX 2
SIRS definitions from [15] (*modified for the
present series of studies [3,11])
The systemic response to infection,
manifested by two or more of the following
conditions as a result of infection:
1. Temperature ≥38 °C or ≤36 °C
2. Heart rate >100 beats/min*
3. Respiratory rate >20 breaths/min
4. White blood cell count >12,000 white blood
cells/µL or <4000 white blood cells/µL
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