epidemiology, treatment and prevention of healthcare-associated urinary tract infections
DESCRIPTION
2011, F. M. E. Wagenlehner, Mete Cek, Kurt G. Naber, Hiroshi Kiyota, Truls E. Bjerklund-JohansenTRANSCRIPT
TOPIC PAPER
Epidemiology, treatment and prevention of healthcare-associatedurinary tract infections
F. M. E. Wagenlehner • Mete Cek •
Kurt G. Naber • Hiroshi Kiyota •
Truls E. Bjerklund-Johansen
Received: 17 April 2011 / Accepted: 23 August 2011 / Published online: 7 September 2011
� Springer-Verlag 2011
Abstract
Objectives Healthcare-associated urinary tract infections
(HAUTIs) are the most frequent healthcare-associated
infections in general hospitals. They are almost exclusively
complicated UTIs, although complicating factors are very
heterogenous. HAUTIs are mainly catheter associated.
Most of them are asymptomatic and do not need antimi-
crobial therapy. However, cross-contamination and cross-
infection may contribute to distribution of resistant uro-
pathogens. The bacterial spectrum of HAUTI is broad, and
antibiotic resistance is common.
Methods The authors reviewed the literature from 2000
to 2010 to determine the epidemiology, prevention and best
treatment strategies for HAUTI. The recommendations
were summarized by determining the level of evidence and
grading each recommendation.
Results The treatment for HAUTI encompasses treatment
for complicating factors as well as antimicrobial chemo-
therapy. At least in serious UTI, adequate initial antibiotic
therapy results in lower mortality. Therefore, the initial
antibiotic regimen must provide sufficient antibiotic cov-
erage. This can only be achieved if the local or regional
bacterial spectrum and antibiotic resistance patterns of
uropathogens are followed continuously. Provisional
microbiological findings, such as reports on Gram-stain or
certain biochemical results, can lead to early stratification
of pathogens and allow a more tailored empiric antibiotic
therapy. Antibiotic therapy of HAUTI has to consider
therapeutic success in the individual patient and prevention
of emergence of antibiotic-resistant mutants. For both
aspects, adequate drug selection and dosing are paramount.
Discussion Antibiotic treatment for HAUTI should fol-
low prudent antibiotic use to prevent emergence of anti-
biotic resistance.
Keywords Healthcare-associated UTI �Nosocomial UTI �Antibiotic treatment for UTI � Emergence of
antibiotic-resistant uropathogens
Summary of recommendations
1. All urinary tract infections (UTI) acquired in an outpa-
tient or in an institutional care setting should be con-
sidered as healthcare-associated UTI (HAUTI) (GoR B).
2. Healthcare-associated asymptomatic bacteriuria
should not be treated with antimicrobials, except
before traumatizing interventions of the urinary tract
and in pregnant women (GoR A).
F. M. E. Wagenlehner
Department of Urology, University Giessen, Giessen, Germany
F. M. E. Wagenlehner (&)
Clinic of Urology, Pediatric Urology and Andrology,
Justus-Liebig-University, Rudolf-Buchheim-Str. 7,
35385 Giessen, Germany
e-mail: [email protected]
M. Cek
Department of Urology, Trakya University,
Edirne, Turkey
K. G. Naber
Technical University, Munich, Germany
H. Kiyota
Department of Urology, Jikei University Affiliated Aoto
Hospital, Tokyo, Japan
T. E. Bjerklund-Johansen
Urology Department, Aarhus University Hospital, Skejby,
Aarhus University, Aarhus, Denmark
123
World J Urol (2012) 30:59–67
DOI 10.1007/s00345-011-0757-1
3. In HAUTI, a wide spectrum of frequently also
multiresistant uropathogenic bacteria has to be con-
sidered (GoR B).
4. For rational empiric therapy, the local susceptibility
pattern of the uropathogens must be continuously
followed and considered (GoR A).
5. A urine specimen and in case of urosepsis also a
blood specimen for culture must be obtained before
initiation of any antibiotic therapy (GoR A).
6. Antibiotic treatment should be initiated after the
results of the susceptibility testing are available,
whenever possible (GoR B).
7. If empiric antibiotic treatment is warranted, it should
be tailored after the results of the susceptibility
testing are available (GoR B).
8. Antibiotics with best performance in biofilm infec-
tion should be selected, and the dosage should be
sufficiently high when treating HAUTI (GoR B).
9. Prevention of catheter-associated UTI is the gold
standard for prevention of HAUTI (GoR A).
10. For prevention of HAUTI in short-term catheteriza-
tion, the following recommendations are to be
considered: (i) staff education about catheter man-
agement; (ii) catheterization only when indicated and
prompt removal of indwelling catheters; (iii) hand-
washing; (iv) catheter insertion with aseptic tech-
nique and sterile equipment; and (v) maintenance of a
closed urinary drainage system (GoR A).
11. For prevention of HAUTI in long-term catheteriza-
tion, the following recommendations should be
considered: (i) hydration; (ii) appropriate catheter
exchange; and (iii) no antimicrobial prophylaxis for
catheter-associated bacteriuria (GoR B).
12. For avoidance of long-term bladder catheterization,
the following methods should be considered:
12.1 in case of incomplete emptying of the bladder:
(i) medications for complete emptying the
urinary bladder, such as cholinergic drugs
and/or alpha-1 adrenergic inhibitors; (ii)
operative deobstruction for benign prostatic
hyperplasia (BPH); and (iii) clean intermit-
tent catheterization (GoR B).
12.2 in case of incontinence: (i) medications for incon-
tinence and (ii) operative treatment for
incontinence (GoR B).
Introduction
A healthcare-associated infection is defined as a localized or
systemic condition that results from an adverse reaction to
the presence of an infectious agent or its toxin and was not
present or incubating prior to the initiation of a healthcare
encounter [1, 2]. The term ‘‘healthcare-associated infec-
tion’’ incorporates the term ‘‘nosocomial’’ or ‘‘hospital
acquired,’’ which refers to infections that occur as a result of
hospital care, but also any infection occurring in an insti-
tutional (long-term facilities, nursing home) or outpatient
care setting. Healthcare-associated urinary tract infections
(HAUTIs) are the most frequent healthcare-associated
infections and account for more than 40% of all healthcare-
associated infections in a general hospital [3, 4] (LoE 2b).
They are mainly catheter associated [3–5] (LoE 2b). Bac-
teriuria should be distinguished from urinary tract infection
and develops in up to 25% of patients who require a urinary
catheter for seven days or more, with a daily risk of 5% [5]
(LoE 3). Most of the catheter-associated bacteriuria are
asymptomatic [6] (LoE 3) and therefore do not need anti-
biotic therapy. However, the pathogens are fully exposed to
the healthcare setting (nosocomial) environment, including
the selective pressure of antibiotic or antiseptic substances.
Unfortunately, many studies do not differentiate between
symptomatic UTI and asymptomatic bacteriuria. HAUTI
comprises perhaps the largest institutional reservoir of
antibiotic-resistant pathogens [5] (LoE 3).
The aim of this review is to determine the epidemiology,
prevention and best treatment strategies for HAUTI and
provide evidence graded recommendations.
Methods
This manuscript was published in part originally in: Naber
KG, Schaeffer AJ, Heyns CF, Matsumoto T, Shoskes DA,
Bjerklund Johansen TE (eds) Urogenital Infections. Euro-
pean Association of Urology—International Consultation
on Urological Diseases, 1st edition 2010, Arnhem, The
Netherlands, ISBN:978-90-79754-41-0 [7]. The review is
based on a systematic literature search for the years
2000–2010 in PubMed. Two searches were performed
using Boolean logic structure: (1) surveillance AND sus-
ceptibility AND nosocomial urinary tract infection (for
search, the term ‘‘nosocomial’’ was used instead of
‘‘healthcare associated’’) and (2) randomized clinical trials
AND nosocomial urinary tract infection AND antibiotic
therapy. The first search revealed 55 publications. There
were several local or national surveillance studies, but only
three multinational studies were found and used for this
review. The second search revealed 15 publications. No
prospective controlled, randomized therapeutic study was
found, in which only patients with nosocomial UTI were
treated or such patients were substratified. Only one study
investigated the effect of antibiotic prophylaxis at urinary
catheter removal, which was included into this review, and
one study investigated the effect of an antibiotic-coated
60 World J Urol (2012) 30:59–67
123
urinary catheter on prophylaxis of nosocomial UTI, which
was included into this review. These publications were
augmented with publications known by the authors.
The studies were rated according to their level of evi-
dence, and the strength of the recommendations was graded
according to the standards of the International Consultation
on Urological Diseases [8, 9].
Epidemiology
The incidence of healthcare-associated infections has
stayed more or less stable over the last two decades.
However, certain aspects of patient care have changed
during this period. As minimally invasive techniques
develop and patient care improves, patients are being
treated either on an outpatient basis or they stay in hos-
pitals for shorter periods. Particularly in urology, there is a
wide range of operations, which allow the patient to be
discharged within 48 h of operations. This has two
important implications on the incidence of healthcare-
associated infections: (1) More elderly patients with
comorbidities are hospitalized [10, 11] and (2) shorter
hospital stays make it difficult to assess the true frequency
of healthcare-associated infections. The incubation periods
of certain infections (e.g., surgical site infections) are
sometimes longer than the hospital stay of patients. It is
thus more preferable to calculate the incidence of health-
care-associated infections on the basis of patient days,
rather than actual number of admissions [12]. The
denominator can also be the number of patients at risk, or
days of indwelling catheterization [13]. The rate of noso-
comial infections per 1,000 patients’ days in the USA was
calculated to be 9.8 in 1995 [12, 13]. More recent esti-
mates (for 2009) exhibit a much more detailed analysis and
are therefore not comparable to previous overall estimates
[14]. On the other hand, the incidence of nosocomial uri-
nary infections in European countries was found to be 3.55
episodes/1,000 patient days and the prevalence was esti-
mated to be 10.65/1,000 [15].
The prevalence of HAUTI in urological departments
was 11% in the combined analysis of the Pan European
Prevalence (PEP) study and the Pan Euro-Asian Prevalence
(PEAP) study [16]. The largest group was asymptomatic
bacteriuria (29%) followed by cystitis (26%), pyelone-
phritis (21%) and urosepsis (12%). The prevalence of
HAUTIs was found to be 14.7% in the Global Prevalence
Study on Infections in Urology (GPIU) 2008 also showing
a rising percentage of urosepsis from 9.3% in 2006 to
21.8% in 2008, while the prevalence of HAUTI stayed
more or less stable around 14% in the same period [17].
This suggests that prophylactic measures in various urol-
ogy clinics may not be appropriate [18].
Risk factors
Several characteristics related to the healthcare provider,
the patient and the procedures are known to increase the risk
of HAUTI. The most important risk factors for HAUTI are
an indwelling catheter and the duration of catheterization
[19]. Other significant risk factors are (1) UTI during the
previous 12 months; (2) urinary tract obstruction; (3) uri-
nary stones; (4) previous antibiotic usage within the last
3 months; and (5) hospitalization within the last 6 months
due to any reason [19]. The study also showed that for
patients having more than three risk factors, there was a
significantly increased risk of having a Candida sp., Kleb-
siella sp. or Pseudomonas sp. as a causative pathogen, when
compared to those patients with three or less risk factors.
Another recent study also found strong evidence
between HAUTI and prolonged length of stay (OR 5.28),
urinary catheter (OR 5.16) [20], unresolved spinal injury
(OR 4.07), fracture/dislocation on admission (OR 3.34),
transfer to/from another hospital (OR 2.9), underlying
neurologic disease (OR 2.59), some assistance required
prior to admission (OR 2.58), previous stroke (OR 1.94)
and male sex was protective (OR 0.44) [20]. Information
on the effectiveness of risk-reducing strategies in those risk
groups is now warranted. Studies suggested also the
severity score of hospitalized patients as an important risk
factor for the development of HAUTI [11, 21]. On the
other hand, immunosuppressant therapy within 14 days,
history of malignancy, cigarette smoking in the past and
male sex are shown to be risk factors for healthcare-asso-
ciated urinary tract-related bacteremia [22].
Bacterial spectrum
Whereas community-acquired UTI are often uncompli-
cated, almost all HAUTIs are complicated infections with
structural or functional abnormalities within the urinary
tract, such as indwelling catheters or some kind of urinary
obstruction. The bacterial etiology of UTI differs markedly
between uncomplicated and complicated UTIs, which is
mainly due to the fact that bacteria causing uncomplicated
UTI are highly selected clones with an array of virulence
factors, which are not required to such an extent in bacteria
causing complicated UTI [23].
Bacterial spectrum in complicated HAUTI
The bacterial spectrum of complicated HAUTIs comprises
a wide range of Gram-negative and Gram-positive species.
The bacterial spectrum can vary geographically, over the
time and between distinct specialities at the same institu-
tion [24] (LoE 3).
World J Urol (2012) 30:59–67 61
123
Bacterial spectrum of HAUTI in North America
(SENTRY study)
The SENTRY antimicrobial surveillance program, initiated
in 1997, has chronologically examined urinary pathogens
collected from hospitalized patients from different hospital
departments across North America and thus provides
insight into pathogen frequency and resistance rates [25]
(LoE 3). A surveillance study based on 1998 data encom-
passed 31 North American institutions, which examined
1,510 urinary isolates from hospitalized patients from dif-
ferent departments [26] (Table 1).
Bacterial spectrum of HAUTI in Europe
(ESGNI-003 study)
A European multicenter one-day prevalence study on
HAUTI of patients from different hospital departments
tested 607 uropathogens from 228 hospitals throughout
Europe [27] (LoE 2b). Patients from different departments
throughout the hospital were evaluated (Table 1).
Bacterial spectrum of HAUTI in urological patients
in Europe (PEP-study)
A European multicenter one-day prevalence study on
HAUTI in urology tested 320 uropathogens from 232
urological departments throughout Europe [19] (LoE 3)
(Table 1).
Antibiotic resistance
Since antibiotics have been introduced into clinical medi-
cine, antibiotic-resistant bacteria have evolved. The epi-
demiology of antibiotic-resistant bacteria, however, varies
from region to region, from speciality to speciality, from
infection type to infection type and from time to time.
Antibiotic resistance in complicated HAUTI
Healthcare-associated uropathogens are frequently subject
to antibiotic pressure and cross-infection [28] (LoE 2b).
The influence of these parameters can vary between
regions and specialities [24] (LoE 3). Different species of
uropathogens show distinct abilities to develop antibiotic
resistance.
Antibiotic resistance in HAUTI in North America,
Latin America and Europe (SENTRY study)
In the SENTRY study, which was a laboratory-based study,
a central reference laboratory was employed using NCCLS
(National Committee for Clinical Laboratory Standards)
criteria [26] (LoE 3). Strains were sent from the local
microbiology laboratories. Global resistance rates (com-
bined resistance of E. coli, Klebsiella spp., P. aeruginosa
and Enterococci) in North America for Ampicillin,
Amoxicillin/clavulanate, Trimethoprim/Sulfamethoxazole
and Ciprofloxacin were 59, 31, 43 and 29%, respectively.
Global resistance rates in Latin America for Ampicillin,
Amoxicillin/clavulanate, Trimethoprim/Sulfamethoxazole
and Ciprofloxacin were 62, 36, 38 and 32%, respectively.
Global resistance rates in Europe for Ampicillin, Amoxi-
cillin/clavulanate, Trimethoprim/Sulfamethoxazole and
Ciprofloxacin were 62, 36, 38 and 32%, respectively
(Table 1).
Antibiotic resistance in HAUTI in Europe
(ESGNI-003 study)
The European Study Group on Nosocomial Infections
(29 countries) also evaluated antimicrobial susceptibility
against hospital-acquired urinary isolates [27] (LoE 2b).
Sensitivity assays were not performed in a central labora-
tory, and local results of susceptibility testing were taken at
face value. During 1999, 607 organisms from 522 patients
with HAUTI were tested. For E. coli, resistance rates were
comparable to those observed from the North American
SENTRY experience (Table 1): TMP/SMX (28%), ampi-
cillin (55%), ciprofloxacin (9%) and gentamicin (6%).
However, it is worth noting that non-European Union
countries tended to have higher rates of E. coli resistance
than European Union countries.
In particular, amikacin, ceftazidime and cefepime were
the most active agents ([90% susceptible), imipenem and
tobramycin were moderately active ([85% susceptible)
and ciprofloxacin and gentamicin were the least active
(*75% susceptible). In contrast, P. aeruginosa isolates
from non-European Union countries (e.g., Estonia, Serbia)
showed resistance rates of over 50% for fluoroquinolones
and non-amikacin aminoglycosides. The authors specu-
lated that this high rate of resistance to pseudomonal
strains might be explained by the lack of strict antimi-
crobial policies in hospitals within non-European Union
countries.
Antibiotic resistance in HAUTI in urological patients
in Europe (PEP-study)
The PEP-study also evaluated resistance rates of uropath-
ogens causing HAUTI in urological patients [19] (LoE 3).
However, there was no reference laboratory, and different
standards were employed for testing of the strains (178
hospitals employed NCCLS criteria, 34 DIN (Deutsches
Institut fur Normung) criteria, and 20 other criteria) and not
62 World J Urol (2012) 30:59–67
123
all hospitals have tested all antibiotics. Global resistance
rates for the total bacterial spectrum were as follows
(Table 1): Ampicillin 51%, ampicillin ? beta-lactamase
inhibitor 30%, piperacillin 21%, piperacillin/tazobactam
15%, cefazolin 44%, cefuroxime 25%, ceftazidime 17%,
cefepime 21%, imipenem 7%, gentamicin 34%, amikacin
14%, ciprofloxacin 34% and TMP/SMZ 45%.
In all these studies, increasing resistance rates were
found for some species like E. coli, but not for all uro-
pathogens. However, resistance rates may vary substan-
tially between regions. Additionally, the results of those
studies were published almost 10 years ago, and more
recent published data on HAUTI are missing. Therefore,
timely, local, hospital-based surveillance of the bacterial
spectrum and antibiotic sensitivity is paramount for a
rational empiric therapy.
Treatment for HAUTI
As mentioned earlier, HAUTI is mainly catheter associated.
HAUTI has to be distinguished from asymptomatic bacte-
riuria, which does not need antibiotic therapy according to
the current guidelines, except before an traumatizing inter-
vention of the urinary tract and in pregnant women [29, 30]
(LoE 1a). However, by cross-contamination and cross-
infection healthcare-associated asymptomatic bacteriuria
may also contribute significantly to the distribution of
Table 1 Antimicrobial spectrum of healthcare-associated uropathogens (C2%) from distinct surveillance studies
Name of study SENTRY [33] SENTRY [33] SENTRY [33] ESGNI-003 [27] PEP-study [19]
Regions of the world North America Latin America Europe Europe Europe
Year of surveillance 2000 2000 2000 2000 2003
Type of surveillance Longitudinal Longitudinal Longitudinal Cross-section Cross-section
Origin of samples Microbiology
laboratories
Microbiology
laboratories
Microbiology
laboratories
Different departments in the
hospital
Urology
departments
Number of pathogens n = 1,466 n = 531 n = 783 n = 607 n = 320
Species %
E. coli 43 60 46 36 35
Klebsiella spp. 12 12 9 8 10
Pseudomonas spp. 7 6 9 7 13
Proteus spp. 6 7 10 8 7
Enterobacter spp. 3 4 4 4 3
Citrobacter spp. 4 2 2 2 n.r.
Enterococcus spp. 16 4 13 16 9
Staphylococcus spp. 6 3 3 4 4
Candida spp. n.r. n.r. n.r. 9 4
Resistance rates of
antibiotics %
Ampicillin 59e 62e 65e 66a 51
Ampicillin ? BLI 31e 36e 36e 29a 30
TMP/SMZ 43e 38e 48e 32a 45
Ciprofloxacin 29e 32e 29e 17b 34
Gentamicin n.r. n.r. n.r. 18 34
Ceftazidime n.r. n.r. n.r. 13c 17
Amikacin n.r. n.r. n.r. 19c 14
Piperacillin/tazobactam n.r. n.r. n.r. n.r. 15
Imipenem n.r. n.r. n.r. 14c 7
Vancomycin n.r. n.r. n.r. 1d n.r.
n.r. Not reporteda Gram-negative bacteria excluding P. aeruginosab Gram-negative bacteriac P. aeruginosad Enteroccocie E. coli, Klebsiella spp., P. aeruginosa, Enterococci
World J Urol (2012) 30:59–67 63
123
resistant uropathogens throughout the institution (nursing
home and hospital) [28] (LoE 2b) and also throughout the
community in case of an outpatient care setting. Therefore,
healthcare-associated asymptomatic bacteriuria may be an
important factor for the spread of resistant uropathogens and
should therefore be included into a systematic (not routine)
surveillance. But in general, antibiotic therapy should only
be considered for symptomatic HAUTI. In some situations,
however, the distinction between healthcare-associated
asymptomatic bacteriuria and symptomatic HAUTI may be
difficult, e.g., intensive care medicine, patients with spinal
cord injury, physically and mentally handicapped (geriatric)
patients or children in young age. Careful consideration of all
clinical parameters is necessary in those instances before
antibiotic therapy is initiated. On the other hand, if systemic
signs or symptoms such as fever or chills appear the urinary
tract should be thoroughly investigated.
General aspects of antibiotic therapy of UTI
In the antimicrobial treatment of uncomplicated UTIs, the
rapid elimination of the pathogen is most important. In
complicated HAUTIs, the primary goal of antibiotic ther-
apy is to limit the infection and prevent the emergence of
resistant mutants.
Drusano and Craig determined four parameters for the
rational dosing of an antibiotic in a population [31]:
1. the minimal inhibitory concentration (MIC) of the
clinical isolates.
2. the pharmacokinetic (pk) profile.
3. the pharmacodynamic (pd) profile.
4. the protein binding of the applied antibiotic.
The distribution of the MIC values of nosocomial clin-
ical isolates is the greatest variable parameter, and the
MICs vary geographically and by time [32, 33] (LoE 2b).
The other three parameters are usually determined from
Phase I to III studies. There is, however, a surprisingly high
interindividual variation. Certain subgroups of patients,
however, are not studied, and recommendations for anti-
biotic therapy must be extrapolated from the results of
other related groups. An additional 5th parameter is
extremely important for the treatment of HAUTI. In many
cases of complicated UTIs, biofilm infection is predomi-
nant, which leads to reduced susceptibility of the pathogens
[34] (LoE 2b). Antimicrobial therapy in complicated UTIs
may only kill the bacteria dissolved from the biofilm
(planktonic form) and thus inhibits the spread of the
infectious process. An accompanying urological therapy
must aim to remove the biofilm. In any case, antibiotics
with best performance in biofilm infection should be
selected and the dosage should generally be high when
treating complicated HAUTIs [35]. The dosage should
even be sufficiently high enough to eradicate also the first
step resistant mutants [36] (LoE 3).
At least in severe UTIs, adequate initial antibiotic
therapy results in lower mortality compared with inade-
quate antibiotic treatment [37] (LoE 3). Susceptibility
testing should be carried out in any case of HAUTI, and if
possible, the results should be awaited before treatment.
However, in severe infections, an initial empiric therapy
must be instigated immediately after microbiological
sampling. Susceptibility testing can serve in these cases to
narrow the antibiotic coverage. Provisional microbiological
findings, such as reports on Gram-stain or certain bio-
chemical results, such as oxidase, coagulase and catalase,
can lead to early stratification of pathogens and allow a
more tailored empiric antibiotic therapy [38] (LoE 3).
Prudent use of antimicrobials may also help to reduce the
selection of resistant pathogens to a minimum.
Antibiotic selection for therapy of complicated HAUTI
and urosepsis
Antibiotics with an enlarged antibacterial spectrum are
necessary for initial empiric treatment in severe cases [39]
(LoE 4). The empiric parenteral treatment could start with
a cephalosporin group 3a, a fluoroquinolone with good
renal excretion or with an aminopenicillin in combination
with a beta-lactamase inhibitor. If clinical improvement
fails after 2–3 days, treatment should be switched to a
pseudomonas active acylaminopenicillin/beta-lactamase
inhibitor, a group 3b cephalosporin or a group 1 carbape-
nem. Other reasons for treatment failure, such as persistent
complicating factors, other infections or non-infectious
sources, should also be taken into account and be
re-evaluated. Local and regional variations in resistance
must be also considered for empiric treatment.
The use of parenteral antibiotics is determined by the
general condition of the patient (e.g., nausea and vomiting)
and the severity of the infection; oral antibiotics can be
continued as soon as the clinical situation has improved.
After the results of the susceptibility testing have arrived,
the antibiotic treatment should be aligned accordingly.
Treatment duration should continue for at least 3–5 days
beyond defervescence, dependent on the removal of the
complicating factor. However, this recommendation does
not hold true for the treatment of pyelonephritis with
abscess formation or chronic bacterial prostatitis, which
should usually continue for several weeks.
Prevention of HAUTI
The best treatment is prevention; this is also true for
HAUTI. Since most HAUTIs are catheter associated,
64 World J Urol (2012) 30:59–67
123
optimal management of any indwelling catheter and pre-
vention of catheter-associated UTI should be of highest
priority in urology.
Prevention of HAUTI in short-term indwelling
catheterization
According to CDC guidelines, prevention of catheter-
associated UTI is the gold standard for prevention of
HAUTI [40]. The following have to be considered:
1. staff education about catheter management,
2. catheterization only when indicated and prompt
removal of indwelling catheters,
3. Handwashing,
4. catheter insertion with aseptic technique and sterile
equipment,
5. maintenance of a closed urinary drainage system,
6. silver- or antibiotic-coated urinary catheter may reduce
the risk of catheter-associated bacteriuria [41, 42]
(LoE 1b), but whether this also holds true for episodes
of symptomatic catheter-associated UTI, needs to be
shown, and
7. a short-term antibiotic prophylaxis at urinary catheter
removal may prevent UTI after short-term indwelling
catheterization [43] (LoE 1b), however may increase
the total antibiotic selection pressure for the develop-
ment of antibiotic resistance.
Prevention of HAUTI in long-term indwelling
catheterization
The CDC guidelines mentioned earlier have been developed
only for the patients with short-term indwelling urethral
catheterization. Catheter-associated bacteriuria is ultimately
not avoidable in patients with long-term indwelling cathe-
terization. Since most catheter-associated bacteriuria with
long-term indwelling catheterization are asymptomatic [44]
(LoE 3), prevention of symptomatic episodes is the aim to
look for. The following practical points are recommended,
but the level of evidence is low (LoE 4).
1. Hydration—the increase in urine volume by hydration
results in washout of bacteria from the urinary bladder
and thus inhibiting bacterial growth in the urinary
bladder. Hydration also prevents obstruction of the
urethral catheter due to encrustation.
2. Catheter exchange—routine catheter exchange is usually
performed every 4–6 weeks. However, the optimal
frequency of catheter exchange depends on the individual
patient, because the catheter encrustation sometimes
happens in shorter periods. In these cases, catheter
exchange should be performed more frequently.
3. No antimicrobial prophylaxis—antimicrobial prophy-
laxis can delay the occurrence of catheter-associated
bacteriuria. However, the incidence of drug-resistant
bacteria increases in the presence of antimicrobial
prophylaxis. Therefore, antimicrobial prophylaxis for
prevention of catheter-associated bacteriuria should be
avoided [5] (LoE 4).
Avoidance of long-term indwelling catheterization
To prevent catheter-associated UTI, long-term indwelling
catheterization should be avoided at the first place. There
are two frequent indications for long-term bladder
catheterization:
• incomplete emptying of the bladder
and
• non-obstructive incontinence.
In both indications attempts, such as (1) medications for
complete emptying the urinary bladder, (2) operative tech-
niques such as deobstruction in case of prostatic obstruction
in males [45, 46], or pelvic floor reconstruction in case of
pelvic floor disorders, such as cystocele formation, (3) clean
intermittent catheterization; or (4) urethral stent for benign
prostatic enlargement [47, 48] (LoE 3), [49, 50] (LoE 3) may
be considered. There is little evidence whether clean inter-
mittent catheterization prevents symptomatic UTIs [51]
(LoE 4). The frequency of clean intermittent catheterization
may be important for the prevention of UTIs.
Further research
In the past most studies did not distinguish between
healthcare-associated symptomatic UTI and asymptomatic
bacteriuria. There is now agreement that healthcare-asso-
ciated asymptomatic bacteriuria should not be treated with
antimicrobials; therefore, routine screening for bacteriuria
seems to be not indicated. However, its impact to induce
infections when spread to other patients is not well
understood. Prospective studies are needed to clarify,
whether systematic surveillance of healthcare-associated
asymptomatic bacteriuria is recommended and if so, at
what time intervals.
Conclusions
HAUTIs are almost exclusively complicated UTI and
mainly catheter associated. Healthcare-associated asymp-
tomatic bacteriuria should not be treated with antimicrobials
World J Urol (2012) 30:59–67 65
123
except before traumatizing interventions of the urinary
tract and in pregnant women. Besides of an adequate
antibiotic therapy, the complicating factors need to be
treated effectively. For initial empiric therapy, the local
susceptibility profile of common uropathogens such as
E. coli must be known to choose the most appropriate
antibiotic. In case of severe, bacteremic UTI, it has been
shown that an inadequate initial antibiotic regimen has an
elevated mortality. Before initiation of antibiotic therapy, a
urine specimen for culture must be obtained to be able to
adapt the antibiotic regimen to the susceptibility profile.
Increasing antibiotic resistance requires a more prudent use
of antimicrobial drugs also in the treatment of HAUTI.
Conflict of interest The authors declare that they have no conflict
of interest.
References
1. Hooton TM, Carlet JM, Duse AG, Krieger JN, Steele L, Sunak-
awa K (2001) Definitions and epidemiology. In: Naber KG,
Pechere JC, Kumazawa J, Khoury S, Gerberding JL, Schaeffer AJ
(eds) Nosocomial and Health Care Associated Infections in
Urology. Health Publication, Plymouth
2. Horan TC, Andrus M, Dudeck MA (2008) CDC/NHSN surveil-
lance definition of health care-associated infection and criteria for
specific types of infections in the acute care setting. Am J Infect
Control 36(5):309–332
3. Gastmeier P, Kampf G, Wischnewski N, Hauer T, Schulgen G,
Schumacher M et al (1998) Prevalence of nosocomial infections
in representative German hospitals. J Hosp Infect 38(1):37–49
4. Ruden H, Gastmeier P, Daschner FD, Schumacher M (1997)
Nosocomial and community-acquired infections in Germany.
Summary of the results of the First National Prevalence Study
(NIDEP). Infection 25(4):199–202
5. Maki DG, Tambyah PA (2001) Engineering out the risk for
infection with urinary catheters. Emerg Infect Dis 7(2):342–347
6. Tambyah PA, Knasinski V, Maki DG (2002) The direct costs of
nosocomial catheter-associated urinary tract infection in the era
of managed care. Infect Control Hosp Epidemiol 23(1):27–31
7. Wagenlehner FME, Cek M, Kiyota H, Bjerklund-Johansen TE
(2010) Epidemiology, treatment and prevention of health-care
associated urinary tract infections. In: Naber KG, Schaeffer AJ,
Heyns C, Matsumoto T, Shoskes D, Bjerklund-Johansen TE
(eds) Urogenital infections. European Association of Urology—
International Consultation on Urological Diseases, Arnhem,
pp 575–588
8. US Department of Health and Human Services, Public Health
Service, Agency for Health Care Policy and Research (1992)
pp 115–127
9. Abrams P, Khoury S, Grant A (2007) Evidence–based medicine
overview of the main steps for developing and grading guideline
recommendations. Prog Urol 17(3):681–684
10. Levy SB, Marshall B (2004) Antibacterial resistance worldwide:
causes, challenges and responses. Nat Med 10(12 Suppl):S122–
S129
11. Safdar N, Maki DG (2002) The commonality of risk factors for
nosocomial colonization and infection with antimicrobial-resis-
tant Staphylococcus aureus, enterococcus, gram-negative bacilli,
Clostridium difficile, and Candida. Ann Intern Med 136(11):
834–844
12. Weinstein RA (1998) Nosocomial infection update. Emerg Infect
Dis 4(3):416–420
13. National Nosocomial Infections Surveillance (NNIS) (2004)
System Report, data summary from January 1992 through June
2004, issued October 2004. Am J Infect Control 32(8):470–485
14. Cited 2011 02.06.2011. Available from: http://www.cdc.gov/
nhsn/PDFs/dataStat/2010NHSNReport.pdf
15. Bouza E, San Juan R, Munoz P, Voss A, Kluytmans J (2001) A
European perspective on nosocomial urinary tract infections II.
Report on incidence, clinical characteristics and outcome (ES-
GNI-004 study). European Study group on nosocomial infection.
Clin Microbiol Infect 7(10):532–542
16. Bjerklund Johansen TE, Cek M, Naber K, Stratchounski L,
Svendsen MV, Tenke P (2007) Prevalence of hospital-acquired
urinary tract infections in urology departments. Eur Urol
51(4):1100–1112
17. Tandogdu Z, Cek M, Tenke P, Naber K, Bjerklund Johansen TE
(2010) Prevalence of nosocomial urinary tract infections: what
has changed in years. In: European Urology Supplements. 25th
Anniversary EAU congress 2010. European Association of
Urology, Barcelona, p 171
18. Naber KG (2006) Urogenital infections: the pivotal role of the
urologist. Eur Urol 50(4):657–659
19. Johansen TE, Cek M, Naber KG, Stratchounski L, Svendsen MV,
Tenke P (2006) Hospital acquired urinary tract infections in
urology departments: pathogens, susceptibility and use of anti-
biotics. Data from the PEP and PEAP-studies. Int J Antimicrob
Agents 28(Suppl 1):S91–S107
20. Graves N, Tong E, Morton AP, Halton K, Curtis M, Lairson D
et al (2007) Factors associated with health care-acquired urinary
tract infection. Am J Infect Control 35(6):387–392
21. Leone M, Albanese J, Garnier F, Sapin C, Barrau K, Bimar MC
et al (2003) Risk factors of nosocomial catheter-associated uri-
nary tract infection in a polyvalent intensive care unit. Intensive
Care Med 29(7):1077–1080
22. Saint S, Kaufman SR, Rogers MA, Baker PD, Boyko EJ, Lipsky
BA (2006) Risk factors for nosocomial urinary tract-related
bacteremia: a case-control study. Am J Infect Control 34(7):
401–407
23. Dobrindt U, Chowdary MG, Krumbholz G, Hacker J (2010)
Genome dynamics and its impact on evolution of Escherichiacoli. Med Microbiol Immunol 199(3):145–154
24. Tambic A, Tambic T, Kucisec-Tepes N (1996) Prevalence and
antibiotic sensitivity pattern variations of bacterial isolates in
different settings and different periods of time. Acta med Croatica
50:5–10
25. Jones RN, Kugler KC, Pfaller MA, Winokur PL (1999) Charac-
teristics of pathogens causing urinary tract infections in hospitals
in North America: results from the SENTRY Antimicrobial
Surveillance Program, 1997. Diagn Microbiol Infect Dis
35(1):55–63
26. Mathai D, Jones RN, Pfaller MA (2001) Epidemiology and fre-
quency of resistance among pathogens causing urinary tract
infections in 1,510 hospitalized patients: a report from the
SENTRY Antimicrobial Surveillance Program (North America).
Diagn Microbiol Infect Dis 40(3):129–136
27. Bouza E, San Juan R, Munoz P, Voss A, Kluytmans J (2001) A
European perspective on nosocomial urinary tract infections I.
Report on the microbiology workload, etiology and antimicrobial
susceptibility (ESGNI-003 study). European Study Group on
Nosocomial Infections. Clin Microbiol Infect 7(10):523–531
28. Wagenlehner FM, Krcmery S, Held C, Klare I, Witte W,
Bauernfeind A et al (2002) Epidemiological analysis of the
spread of pathogens from a urological ward using genotypic,
phenotypic and clinical parameters. Int J Antimicrob Agents
19(6):583–591
66 World J Urol (2012) 30:59–67
123
29. Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton
TM (2005) Infectious Diseases Society of America guidelines for
the diagnosis and treatment of asymptomatic bacteriuria in adults.
Clin Infect Dis 40(5):643–654
30. Nicolle LE, Zhanel GG, Harding GK (2006) Microbiological
outcomes in women with diabetes and untreated asymptomatic
bacteriuria. World J Urol 24(1):61–65
31. Drusano GL, Preston SL, Hardalo C, Hare R, Banfield C, Andes
D et al (2001) Use of preclinical data for selection of a phase II/
III dose for evernimicin and identification of a preclinical MIC
breakpoint. Antimicrob Agents Chemother 45(1):13–22
32. Kahlmeter G (2003) An international survey of the antimicrobial
susceptibility of pathogens from uncomplicated urinary tract
infections: the ECO.SENS project. J Antimicrob Chemother
51(1):69–76
33. Gordon KA, Jones RN (2003) Susceptibility patterns of orally
administered antimicrobials among urinary tract infection
pathogens from hospitalized patients in North America: com-
parison report to Europe, Latin America. Results from the
SENTRY Antimicrobial Surveillance Program (2000). Diagn
Microbiol Infect Dis 45(4):295–301
34. Goto T, Nakame Y, Nishida M, Ohi Y (1999) Bacterial biofilms
and catheters in experimental urinary tract infection. Int J Anti-
microb Agents 11(3–4):227–231 (discussion 37–39)
35. Pea F, Pavan F, Di Qual E, Brollo L, Nascimben E, Baldassarre
M et al (2003) Urinary pharmacokinetics and theoretical phar-
macodynamics of intravenous levofloxacin in intensive care unit
patients treated with 500 mg b.i.d. for ventilator-associated
pneumonia. J Chemother 5(6):563–567
36. Zhao X, Drlica K (2008) A unified anti-mutant dosing strategy.
J Antimicrob Chemother 62(3):434–436
37. Elhanan G, Sarhat M, Raz R (1997) Empiric antibiotic treatment
and the misuse of culture results and antibiotic sensitivities in
patients with community-acquired bacteraemia due to urinary
tract infection. J Infect 35(3):283–288
38. Wagenlehner E, Niemetz A, Naber G (2003) Spectrum of
pathogens and resistance to antibiotics in urinary tract infections
and the consequences for antibiotic treatment: study of urology
inpatients with urinary tract infections (1994–2001). Urologe A
42(1):13–25
39. Grabe M, Bishop M, Bjerklund-Johansen TE, Botto H, Cek M,
Lobel B, Naber KG, Palou J, Tenke P, Wagenlehner F (2009)
Guidelines on urological infections. In: EAo Urology (ed)
European Association of Urology Guidelines. European Associ-
ation of Urology, Arnhem, pp 1–110
40. Tenke P, Kovacs B, Bjerklund Johansen TE, Matsumoto T,
Tambyah PA, Naber KG (2008) European and Asian guidelines on
management and prevention of catheter-associated urinary tract
infections. Int J Antimicrob Agents 31(Suppl 1):S68–S78
41. Karchmer TB, Giannetta ET, Muto CA, Strain BA, Farr BM (2000)
A randomized crossover study of silver-coated urinary catheters in
hospitalized patients. Arch Intern Med 160(21):3294–3298
42. Al-Habdan I, Sadat-Ali M, Corea JR, Al-Othman A, Kamal BA,
Shriyan DS (2003) Assessment of nosocomial urinary tract
infections in orthopaedic patients: a prospective and comparative
study using two different catheters. Int Surg 88(3):152–154
43. Pfefferkorn U, Lea S, Moldenhauer J, Peterli R, von Flue M,
Ackermann C (2009) Antibiotic prophylaxis at urinary catheter
removal prevents urinary tract infections: a prospective ran-
domized trial. Ann Surg 249(4):573–575
44. Tambyah PA, Maki DG (2000) Catheter-associated urinary tract
infection is rarely symptomatic: a prospective study of 1,497
catheterized patients. Arch Intern Med 160(5):678–682
45. Bach T, Netsch C, Haecker A, Michel MS, Herrmann TR, Gross
AJ (2010) Thulium: YAG laser enucleation (VapoEnucleation) of
the prostate: safety and durability during intermediate-term fol-
low-up. World J Urol 28(1):39–43
46. Lourenco T, Shaw M, Fraser C, MacLennan G, N’Dow J, Pickard
R (2010) The clinical effectiveness of transurethral incision of the
prostate: a systematic review of randomised controlled trials.
World J Urol 28(1):23–32
47. Oesterling JE (1991) A permanent, epithelializing stent for the
treatment of benign prostatic hyperplasia. Preliminary results.
J Androl 12(6):423–428
48. Gottfried HW, Schlmers HP, Gschwend J, Brandle E, Hautmann
RE (1994) Thermosensitive stent (Memotherm) for the treatment
of benign prostatic hyperplasia. Arch Esp Urol 47(9):933–943
49. Ala-Opas M, Talja M, Tiitinen J, Hellstrom P, Heikkinen A,
Nurmi M (1993) Prostakath in urinary outflow obstruction. Ann
Chir Gynaecol Suppl 206:14–18
50. Poulsen AL, Schou J, Ovesen H, Nordling J (1993) Memokath: a
second generation of intraprostatic spirals. Br J Urol 72(3):
331–334
51. Moore KN, Fader M, Getliffe K (2007) Long-term bladder
management by intermittent catheterisation in adults and chil-
dren. Cochrane Database Syst Rev (4):CD006008
World J Urol (2012) 30:59–67 67
123