id000032
10.3205/id000032
urn:nbn:de:0183-id0000327
Review Article
Spectrum and antibiotic resistance of catheter-associated urinary tract infections
Köves
Köves
Béla
B
Dr.
Department of Urology, Jahn Ferenc Dél-Pesti Kórház, Köves utca 2–4, H-1204 Budapest, HungaryDepartment of Urology, South-Pest Hospital, Budapest, Hungary
bkoves@gmail.com
author
Magyar
Magyar
András
A
Department of Urology, South-Pest Hospital, Budapest, Hungary
author
Tenke
Tenke
Peter
P
Department of Urology, South-Pest Hospital, Budapest, Hungary
author
German Medical Science GMS Publishing House
Düsseldorf
610
Urogenital infections and inflammations
20171122
engl
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung).
2195-8831
5
GMS Infectious Diseases
GMS Infect Dis
06
Catheter associated urinary tract infections (CAUTIs) are amongst the most common nosocomial infections and are also considered among the most common complications associated with indwelling urinary catheters. Most catheter associated infections are derived from the patient’s own perineal flora, however the presence of a catheter increases the chance of being colonised by cross transmission of nosocomial bacteria as well. Most episodes of short-term catheter-associated bacteriuria are asymptomatic and are caused by single organisms, while long-term catheterisation promotes multibacterial infections and colonization. With prolonged duration of catheterization bacteriuria is considered universal because of the formation of biofilms on the surface of the catheter. Chronic indwelling catheters are an important reservoir of different multiresistant gram-negative organisms, therefore they are frequently isolated from CAUTIs. Treatment of catheter associated asymptomatic bacteriuria is not recommended because it will only promote the emergence of resistant organisms without effectively clearing the urine of catheterised patients.
Summary of recommendationsRegarding bacterial spectrum and antimicrobal resistance of catheter associated urinary tract infections the following recommendations should be highlighted:Routine urine culture in asymptomatic catheterised patients is not recommended (Gr: B).Treatment of catheter associated asymptomatic bacteriuria is not recommended (Gr: A).
1 IntroductionUrinary tract infections (UTIs) represent at least 40% of all hospital acquired infections with the majority of cases being catheter associated , . In patients without catheters microorganisms that ascend from the urethra are usually of enteric origin (e.g. Escherichia coli and other Enterobacteriaceae). However the presence of a catheter creates a special environment for bacterial colonisation and biofilm formation, which increases the chance of being colonised by non-enteric nosocomial bacteria, like Pseudomonas aeruginosa as well. Therefore it is important to be familiar with the different spectrum of pathogens associated with the presence of an urinary catheter.
2 MethodsWe performed a literature search in the PubMed database from 1970 to 2016 regarding the spectrum and antibiotic resistance of catheter-associated urinary tract infections (CAUTIs) using the following keywords in different combinations: catheter, urinary tract infection, bacteriuria, antibiotic resistance. Only publications written in English were selected. A total of 38 publications were identified through the search. Furthermore, data and recommendations of the European Association of Urology , the European Centre for Disease Prevention, Control and Centers for Disease Control and Prevention, including Guideline for Prevention of Catheter-associated Urinary Tract Infections from 2009 and recommendations for Healthcare-associated Infections (HAIs) were also collected. The recommendations were based on the level of evidence and the grade of recommendation. For this purpose the system modified from the Oxford Centre for Evidence-based Medicine was used .
3 Results3.1 Routes and incidence of colonisation3.1.1 PathogenesisTransurethral ascent of microorganisms is the most common mechanism of UTI development, which provides a logical explanation for the increased risk of infection following bladder catheterisation or instrumentation. Bacteria can ascend through the lumen of the catheters by reflux of urine from the contaminated bags (intraluminal route) or along the extraluminal catheter-urethral surface. At the time of catheter insertion up to 20% of patients will be colonized immediately , . Catheterised patients with catheter associated bacteriuria develop bacteremia in 0.4–4% of cases. In acute care facilities catheter associated UTI is one of the most common causes of bacteremia , , , because of the high frequency of catheterisation. For closed catheter systems the incidence of bacterial colonisation is increased by 3–8% with each day , therefore colonisation is considered universal by the end of the month. The development of bacteriuria is universal within 3–4 days in case of catheters with open-drainage systems. Impairment of the natural defense mechanisms (e.g. obstruction, immunsuppresion), leads to reduction of virulence requirements of any bacterial strain to induce infection.3.1.2 BiofilmBiofilm formation is a universally occuring phenomen on the surface of the catheters in the urinary tract. Biofilms are structured communities of microorganisms encapsulated within a self-developed polymeric matrix adherent to a surface . These bacteria may differ from their planktonic free-floating counterparts in many aspects, such as metabolic rates or antibiotic susceptibility. The formation of biofilms on catheter surfaces is the reason why bacteriuria becomes universal in case of long-term catheterisation. 3.2 Microorganisms and spectrum 3.2.1 Short-term catheterisationShort-term (<30 days) catheter-associated bacteriuria is generally caused by single organisms and is asymptomatic. However it may be polymicrobial in up to 15% of cases , . During initial catheter insertion or catheter exchange, transient asymptomatic bacteraemia is common in chronically catheterised patients . The risk of bacteraemia during initial catheter insertion may be similar, whether there is a pre-existing UTI (7%) or sterile urine (8.2%) , (IIa). The incidence of febrile UTI and bacteraemia is relatively low since colonisation of urethral catheters is caused mainly by less virulent organisms and a non-obstructed catheter effectively drains the infection. The bacterial spectrum reflects the locally prevailing flora (eg. community, hospital). According to the European and Asian guidelines on management and prevention of catheter-associated urinary tract infections the most frequently occurring bacteria during short-term catheterisation are E. coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, Staphylococcus epidermidis, Enterococcus spp. and Candida spp. .Pyuria, which however varies by organism, has no diagnostic value, and is present in most cases of catheter-associated bacteriuria.3.2.2 Long-term catheterisationIndwelling catheterisation lasting 30 days or longer is defined as ‘long-term’ or ‘chronic’. With prolonged duration of catheterisation biofilm formation on the catheter surface occurs universally , , . As a consequence microorganisms may acquire increased resistance against antimicrobials and become almost impossible to eradicate without removing the catheter. In long-term catheterised patients polymicrobial bacteriuria occures in up to 95% of the cases, with usually <![CDATA[3–5 i</PlainText></TextGroup>solated organisms. During long-term catheterisation, the commonest bacteria is <Mark2>E. coli</Mark2>. Other associated flora include <Mark2>Providencia stuartii</Mark2>, <Mark2>Pseudomonas</Mark2>, <Mark2>Proteus</Mark2>, <Mark2>Morganella</Mark2> and <Mark2>Acinetobacter</Mark2>, <Mark2>Enterococcus</Mark2> and <Mark2>Candida</Mark2> spp. <TextLink reference="10"></TextLink>.</Pgraph><Pgraph>While the catheter remains in situ, the spectrum of free-floating microorganisms and bacteria in the biofilms shows a dynamic turnover. Bergqvist et al. found that one-quarter of the samples obtained by an indwelling catheter did not show complete agreement with the bladder aspiration samples suggesting that some organisms may colonise the catheter only <TextLink reference="21"></TextLink>.</Pgraph><SubHeadline2>3.2.3 Occuring bacteria</SubHeadline2><Pgraph>Similarly to the bacterial spectrum of uncomplicated UTIs, <Mark2>E. coli</Mark2> is the most common pathogen in the presence of a catheter as well. However in the presence of a catheter we find higher proportions of other bacteria, especially a higher rate of gram-positive pathogens. </Pgraph><Pgraph>The National Healthcare Safety Network (NHSN) is a national surveillance system for patient and healthcare personnel safety in the USA. It aims to surveil selected HAI data at locations other than intensive care units, in hospitals and other types of healthcare facilities. In hospitals reporting to the NHSN between 2006–2007, the most frequent pathogens associated with the presence of an indwelling catheter were <Mark2>E. coli</Mark2> (21.4%) and <Mark2>Candida</Mark2> spp. (21.0%), followed by <Mark2>Enterococcus</Mark2> spp. (14.9%), <TextGroup><Mark2>P. a</Mark2></TextGroup><Mark2>eruginosa</Mark2> (10.0%), <Mark2>K. pneumoniae</Mark2> (7.7%), and <Mark2>Enterobacter</Mark2> spp. (4.1%) and <Mark2>Acinetobacter baumannii</Mark2> (1,2%). A smaller proportion was caused by other gram-negative bacteria and <Mark2>Staphylococcus</Mark2> spp. <TextLink reference="22"></TextLink>. Moreover at one US tertiary care academic centre <Mark2>Enterococcus</Mark2> spp. (28.4%) and <Mark2>Candida</Mark2> spp. (19.7%) were reported to be the most common pathogens <TextLink reference="9"></TextLink>, <TextLink reference="23"></TextLink>.</Pgraph><Pgraph>The persistence of <Mark2>E. coli</Mark2> strains is related to the presence of Type 1 pili, an adhesin for uroepithelium as well as the Tamm-Horsfall protein. Colonising <Mark2>E. coli</Mark2> strains lack P fimbriae in most cases of catheter-associated infections <TextLink reference="24"></TextLink>.</Pgraph><Pgraph><Mark2>Enterococcus</Mark2> species, especially <Mark2>Enterococcus faecalis</Mark2> and <Mark2>Enterococcus faecium</Mark2> are among the leading causes of hospital-acquired UTIs <TextLink reference="22"></TextLink>, <TextLink reference="25"></TextLink>. Many enterococcal isolates can produce biofilms. Catheter implantation results bladder inflammation and causes fibrinogen release and accumulation onto the catheter. <Mark2>E. faecalis</Mark2> takes advantage of the presence of fibrinogen and uses it as a resource through the production of proteases <TextLink reference="26"></TextLink>.</Pgraph><Pgraph><Mark2>P. mirabilis</Mark2> is an organism of unique importance for CAUTIs. It is not typical in patients undergoing short term catheterization <TextLink reference="27"></TextLink>, however the longer a catheter is in place the more likely <Mark2>P. mirabilis</Mark2> will be present. It was found in about 40% of urine samples collected from patients with chronic indwelling catheters <TextLink reference="9"></TextLink>. <Mark2>P. mirabilis</Mark2> has a uniquely strong biofilm forming activity compared to other uropathogens <TextLink reference="28"></TextLink>, and it is also a very potent urease producer. <Mark2>P. mirabilis</Mark2> hydrolyzes urea several times faster than other pathogens with urease activity <TextLink reference="29"></TextLink>. Organisms producing urease may cause a crystalline biofilm <TextLink reference="30"></TextLink>, <TextLink reference="31"></TextLink>, which is similar to struvite stones, and it is frequently associated with catheter encrustation and obstruction <TextLink reference="32"></TextLink>. Other urease producing species include <Mark2>P. aeruginosa</Mark2>, <Mark2>K. pneumoniae</Mark2>, <Mark2>Morganella morganii</Mark2>, other <Mark2>Proteus</Mark2> species, some <Mark2>Providencia</Mark2> spp. and some strains of <Mark2>Staphylococcus aureus</Mark2> and coagulase negative <Mark2>staphylococci</Mark2> <TextLink reference="33"></TextLink>. </Pgraph><Pgraph>Patients with urinary catheter also have an increased risk of UTI due to <Mark2>Pseudomonas</Mark2> spp. <TextLink reference="8"></TextLink>. <Mark2>P. aeruginosa</Mark2> is an opportunistic human pathogen, which causes infections through biofilm formation on the surface of indwelling catheters. It utilizes a distinct mechanism to form biofilms, independent of exopolysaccharides during CAUTIs <TextLink reference="34"></TextLink>.</Pgraph><Pgraph>Another organism rarely found outside of the catheterised urinary tract is <Mark2>Providencia stuartii</Mark2> <TextLink reference="20"></TextLink>. For this organism, the adhesins MR/K are more common <TextLink reference="35"></TextLink>, <TextLink reference="36"></TextLink>. <Mark2>Acinetobacter</Mark2> is a group of bacteria commonly found in soil and water. Outbreaks of <Mark2>Acinetobacter</Mark2> infections including occasionally urinary tract infections typically occur healthcare settings treating very ill patients and rarely occur outside of healthcare settings <TextLink reference="37"></TextLink>.</Pgraph><Pgraph><Mark2>Candida albicans</Mark2> readily causes a clinical UTI via the haematogenous route, but this is also can cause ascending infection if an indwelling catheter is present, or following antibiotic therapy <TextLink reference="10"></TextLink>. </Pgraph><Pgraph>Candiduria develops in 3%–32% of patients with short-term catheterisation <TextLink reference="13"></TextLink>. In case of long-term catheterization the incidence of candiduria was 17% in a single study reporting on a population of individuals with spinal cord injury or multiple sclerosis <TextLink reference="38"></TextLink>. The US NHSN no longer counts candida CAUTI in its surveillance definitions.</Pgraph><SubHeadline>3.3 Antimicrobial resistance in the presence of a catheter</SubHeadline><Pgraph>The increasing antimicrobial resistance against different antimicrobials is a common problem with urinary pathogens. Chronic indwelling catheters are an important reservoir of different multiresistant gram-negative organisms, such as extended spectrum beta-lactamase (ESBL) producing <Mark2>Enterobacteriaceae</Mark2> <TextLink reference="39"></TextLink> or carbapenem-resistant <Mark2>Enterobacteriaceae</Mark2> (CRE) <TextLink reference="40"></TextLink>. Therefore multir<TextGroup><PlainText>es</PlainText></TextGroup>istant organisms are often causes of CAUTIs.</Pgraph><Pgraph>One of the most important factors leading to increasing bacterial resistance is the fact that patients with indwelling urinary catheters often receive antimicrobials, usually for indications other than urinary tract infection <TextLink reference="9"></TextLink>. Due to this intense antimicrobial exposure, antimicrobial resistant bacteria are frequently isolated from catheterised urine samples. Conversely, pathogens colonizing the drainage bags of catheterized patients were found to be a source for outbreaks of resistant organisms in acute care facilities <TextLink reference="13"></TextLink>, <TextLink reference="41"></TextLink>. The urine of residents with chronic indwelling catheters was found to be the most common site of isolation of resistant gram-negative organisms in nursing home setting as well <TextLink reference="39"></TextLink>, <TextLink reference="42"></TextLink>. Consequently, current data do not support the treatment of catheter associated asymptomatic bacteriuria because it will only promote the emergence of resistant organisms <TextLink reference="43"></TextLink>, <TextLink reference="44"></TextLink> without effectively clearing the urine of catheterised patients.</Pgraph><Pgraph>In the annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention (2006–2007) 24,8% of <Mark2>E. coli</Mark2> isolates and 33,8% of <Mark2>P. aeruginosa</Mark2> isolates from CAUTI cases were fluoroquinolone-resistant. Against ceftriaxone, resistances of <Mark2>E. coli</Mark2> and <Mark2>K. pneumoniae</Mark2> were 5,5% and 21,2%, respectively. Resistance rates were relatively high even against carbapenems in the presence of a catheter: <Mark2>E. coli</Mark2> 4%, <Mark2>K. pneumoniae</Mark2> 10%, <Mark2>P. aeruginosa</Mark2> 25% and <Mark2>A. baumannii</Mark2> 25,6%. Significant resistance was found against vancomycin (6,1%) and ampicillin (3,1%) in case of <Mark2>E. faecalis</Mark2> as well.</Pgraph></TextBlock>
<TextBlock linked="yes" name="4 Further research">
<MainHeadline>4 Further research</MainHeadline><Pgraph>Further research has to be aimed to develop antimicrobial agents that are also effective against bacteria enclosed in the biofilms. Creating an ideal catheter surface modification which can resist bacterial adhesion and biofilm formation in long-term catheterisation is also a challenge of the future.</Pgraph></TextBlock>
<TextBlock linked="yes" name="5 Conclusion">
<MainHeadline>5 Conclusion</MainHeadline><Pgraph>Urinary catheters have long been recognized as major risk factor for developing healthcare associated UTIs. There is different spectrum of causative pathogens in the presence of a catheter due to biofilm formation and different resistance patterns from what we see in the urinary tract without a foreign body. Pathogens within the biofilm are well protected from antibiotics and from the host defense. Traditional microbiologic laboratory testing can detect planktonic free-floating bacteria within the urine, but pathogens within the biofilm will not be easily detected with routine methods. Since antimicrobal therapy in catheterised patients induces bacterial resistance and will be associated with the development of multi-resistant organisms, prudent antibiotic administration strategy, catheter management and prevention of CAUTIs should be considered high priority. Treatment of asymptomatic bacteriuria in catheterized patients should be avoided as this can only aggravate the problem of antimicrobial resistance in healthcare.</Pgraph></TextBlock>
<TextBlock linked="yes" name="Note">
<MainHeadline>Note</MainHeadline><Pgraph>This article is also to be published as a chapter of the Living Handbook „Urogenital Infections and Inflammations“ <TextLink reference="45"></TextLink>.</Pgraph></TextBlock>
<TextBlock linked="yes" name="Competing interests">
<MainHeadline>Competing interests</MainHeadline><Pgraph>The authors declare that they have no competing interests.</Pgraph></TextBlock>
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