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© Borgis - Postępy Nauk Medycznych 9/2016, s. 632-638 | DOI: 10.5604/08606196.1219840
Beata Semeniuk1, Zbigniew Lewandowski2, Łukasz Chabros3, Magdalena Durlik1, *Teresa Bączkowska1
Urinary tract infections with alert pathogens in allogeneic kidney transplant recipients
Zakażenie układu moczowego szczepami alarmowymi u chorych po zabiegu przeszczepienia nerki
1Department of Transplantation Medicine, Nephrology and Internal Medicine, Medical University of Warsaw
Head of Department: Professor Magdalena Durlik, MD, PhD
2Department of Epidemiology, Medical University of Warsaw
Head of Department: Professor Józef P. Knap, MD, PhD
3Department of Medical Microbiology, The Infant Jesus Teaching Hospital, Warsaw
Head of Department: Professor Grażyna Młynarczyk, MD, PhD
Streszczenie
Wstęp. Zakażenie układu moczowego szczepami alarmowymi u chorych po zabiegu przeszczepienia nerki stanowi istotny problem kliniczny.
Cel pracy. Ocena częstości występowania, czynników ryzyka oraz wpływu rodzaju szczepu alarmowego wywołującego zakażenie układu moczowego (UTI) na czynność nerki przeszczepionej.
Materiał i metody. Analizie poddano 132 chorych po zabiegu przeszczepienia nerki hospitalizowanych z powodu UTI.
Wyniki. Dodatni wynik posiewu moczu szczepami alarmowymi uzyskano u 29,6% chorych z UTI. Obecność cewnika JJ była związana z ponad 3-krotnie zwiększonym ryzykiem rozwoju UTI szczepami alarmowymi (OR 3,69; p < 0,007). UTI wywołane Klebsiella, Enterococcus faecalis, faecium było związane ze zwiększonym ryzykiem rozwoju szczepów alarmowych, OR wynosiło odpowiednio: 9,89 (p < 0,001), 2,57 (p < 0,053) oraz 11,13 (p < 0,001). UTI wywołane przez Escherichia coli było związane ze zmniejszonym ryzykiem rozwoju szczepu alarmowego OR 0,12 (p < 0,001). Zakażenie szpitalne, okres bezpośredni po transplantacji nerki były związane odpowiednio z 5-krotnie (OR 4,72; p < 0,001) oraz ponad 10-krotnie (OR 10,20; p < 0,007) zwiększonym ryzykiem powstania szczepu alarmowego. Chorzy zakażeni szczepami alarmowymi przy przyjęciu do szpitala mieli wyjściowo gorszą czynność nerki przeszczepionej w porównaniu z chorymi zakażonymi szczepem niealarmowym (p < 0,001), aczkolwiek nie obserwowano istotnej różnicy w czynności przeszczepu nerkowego pomiędzy chorymi z UTI wywołanymi szczepami alarmowymi w porównaniu z chorymi z UTI wywołanym przez szczepy niealarmowe pod koniec hospitalizacji.
Wnioski. Zakażenia układu moczowego szczepami alarmowymi stanowią coraz większy problem kliniczny. Należy opracować odpowiednią politykę postępowania z taki chorymi, aby ograniczyć częstość ich występowania.
Summary
Introduction. Multidrug-resistant (MDR) urinary tract infections (UTI) are a major clinical problem after kidney transplantation.
Aim. Data analysis on the incidence, microbiology, risk factors as well as the effects of MDR UTIs on renal function.
Material and methods. The study included 132 renal transplant recipients with UTI.
Results. Positive cultures for alert patogen (AP) were obtained in 29.6% patients. The use of JJ stents was associated with an over 3-fold increase in the risk of MDR infections (OR = 3.69; p < 0.007). Positive culture for Klebsiella, Enterococcus faecalis and faecium was associated with an increased risk of obtaining AP. The odds ratios were as follows: 9.89 (p < 0.001), 2.57 (p < 0.053) and 11.13 (p < 0.001). Escherichia coli infection was associated with reduced risk of AP infection (OR = 0.12; p < 0.001). Community-acquired infections vs hospital-acquired infections was associated with 5 times higher risk of MDR (OR = 4.72; p < 0.001). The risk of infection with AP in patients admitted immediately after KTx was over 10-fold higher compared to those hospitalized for ‘other reasons’ (OR = 10.20; p < 0.007). Patients infected with AP had worse renal function on admission (p < 0.001) compared to those infected with non-alert pathogens. However, no significant differences in renal function were found between patients infected with AP and those infected with non-alert pathogens at the end of hospitalization (p < 0.091).
Conclusions. MDR UTI have become an important clinical problem in patients after kidney transplantation, every efforts should be made to reduce their occurrence.
Urinary tract infection (UTI) in kidney transplant recipients is one of the most common infectious complications encountered in both in- and outpatient setting (36-75%), with about 30% of UTI patients developing sepsis. UTIs can also promote cytomegalovirus (CMV) infections and acute graft rejection as well as exert adverse indirect effects on transplanted kidney function (1, 2).
As a result of recurrent infections and broad-spectrum antibiotic therapy, alert pathogens able to develop defense mechanisms against different groups of antibiotics are often isolated. Microbial resistance to antibiotics is determined by genetic information encoded in chromosomes and/or transportable elements (plasmids, integrons, transposons). Bacterial resistance to a certain group of antibiotics can be intrinsic or acquired via genetic processes (mutations, transfer of genetic information through direct cell-to-cell contact) (3). Microbial resistance to drugs is currently one of the major problems in UTI antibiotic therapy, particularly in hospital-acquired infections. Hospital-acquired UTIs account for 40% of all hospital-acquired infections, including 82% of Gram-negative infections. Hospitalized UTI patients are a reservoir for typical hospital bacterial strains, which are more resistant to antibiotics compared to strains causing other infections (4). The most common mechanisms of antibiotic resistance include:
– ESBL (extended-spectrum β-lactamases) – most often found in Escherichia coli, Klebsiella spp., Enterobacter spp., Seratia spp. and Proteus mirabilis. They confer resistance to penicillins and cephalosporins (except for cephamycins). Of lactam antibiotics, only carbapenems (imipenem, meropenem) are active against these bacterial strains. They probably account for about 40% of UTIs in renal transplant recipients,
– HLAR (high-level aminoglycoside resistance) – the resistance to high aminoglycoside concentrations is acquired and results from the effects of enzymes that modify aminoglycosides. Isolated from Enterococcus strains (Streptococcus, Enterococcus faecalis and Enterococcus faecium), which are naturally resistant to cephalosporins and low aminoglycoside concentrations,
– VRE (vancomycin resistant Enterococcus) – resistance to vancomycin and teicoplanin in Enterococcus strains, which is a major therapeutic problem in hospital-acquired infections,
– MRCNS – methicillin-resistant coagulase-negative Staphylococcus,
– KPC (Klebsiella pneumoniae carbapanemase) – strains of Enterobacteriaceae resistant to carbapenems (imipenem, meropenem, ertapenem) as well as other β-lactam antibiotics (penicillins, cephalosporins). Isolated among the strains of Enterobacteriaceae as well as the family of Pseudomonas, Acinetobacter,
– MRSA – methicillin resistant Staphylococcus aureus,
– AmpC – chromosomal cephalosporinases (constitutive or inducible) – resistance mechanism resulting from the production of chromosomal cephalosporinase encoded by the AmpC gene (AmpC β-lactamase). Most often isolated among E. coli and Klebsiella spp. (5).
Therefore, data analysis on the incidence, microbiology, risk factors as well as the effects of alert pathogen-related UTIs on the function of the transplanted kidney seems to be important not only for medical, but also economic reasons as the costs of both diagnostics and treatment in alert pathogen-related UTIs require considerable financial resources (2, 6-8).
Aim
Data analysis on the incidence, microbiology, risk factors and influence of AP on the renal function of transplanted kidney.
Material and methods
The study included 132 renal transplant recipients hospitalized in the Department of Transplantation Medicine, Nephrology and Internal Medicine between 2010 and 2011, with a positive bacteriological culture and diagnosed UTI on admission. Patients with asymptomatic bacteriuria were excluded from the analysis. Data for the study group is shown in table 1.
Tab. 1. Characteristics of the study group
Factors nx ± SD or
percentage (%)
MedianQ1-Q3
Age (years)13249.0 ± 14.251.337.4-59.2
BMI (kg/m2)10824.2 ± 4.623.820.6-26.5
Female sex13267.4%
Total HD duration (years)1292.8 ± 2.02.01.0-4.0
Recurrent UTIs 13261.4%
Post-transplantation diabetes mellitus13015.4%
ATG/Thymoglobulin1325.3%
JJ stent13216.7%
Urinary tract defects13211.4%
Hospital-acquired infections13231.8%
Reinfection13237.9%
Sepsis 13129.8%
Reasons for hospitalization:
UTI
KTx


132
132


57.6%
20.5%
Deterioration in renal function13211.4%
Other13210.6%
Creatinine levels (mg/dl) 1322.9 ± 2.12.11.6-3.4
eGFR (ml/min/1.73 m2)13228.8 ± 15.726.916.7-38.8
Alert pathogens 13229.6%
x ± SD – mean value ± standard deviation
We have analyzed selected factors potentially determining infections with alert pathogens. These included patient’s medical history (age, sex, BMI, HD duration), perioperative factors such as the use of induction (ATG Fresenius, Thymoglobulin), urinary tract defects, the need for JJ catheter, the reason for hospitalization, hospitalization-related events as well as the type of bacteria present in the urine.
A midstream specimen of urine was collected into a sterile container following a thorough washing of the external genitalia. The urine samples were then either delivered to a microbiological laboratory within 2 hours or stored in the Department for up to 24 hours at 4°C, and then sent to a microbiological laboratory. Urine culture was performed in the Department of Microbiology, Medical University of Warsaw. Data collection was based on a thorough analysis of medical history.
A total of 132 positive urine cultures were obtained in renal transplant recipients who were admitted to the Department due to: UTI, treatment continuation immediately after kidney transplantation (KTx), deterioration in renal function as well as other reasons, such as: transplanted kidney biopsy, anemia, the need for JJ stent placement, weight loss, diarrhea, leukopenia, pleural effusion. Patients with UTI were included in the analysis – every patient could have a medical history of multiple urinary tract infections in the studied period, but only the first infection was evaluated.
Statistical analysis
Statistical analysis was performed to investigate the relationship between factors describing the condition of the patient (age, sex, BMI), pre-hospitalization and hospitalization conditions (diabetes, total HD duration, UTI recurrence, reinfection, the presence of JJ stent, ATG/Thymoglobulin treatment, reasons for hospitalization, hospital-acquired infections, urinary tract defects), medical management after admission and assays: alert pathogens, sepsis, creatinine and eGFR. Logistic regression analysis was used for this purpose. The strength of the relationship between the assessed factors and the risk of infection with alert pathogens was expressed as the odds ratio (OR) with 95% confidence interval (95% CI). In order to assess the differences in creatinine levels and eGFR, the significance of the differences in these parameters (Wilcoxon signed-ranks test) was evaluated for each group, followed by their comparison between the groups of alert and non-alert pathogens (Mann-Whitney U test). The results are presented as a mean value ± SD and as a median with quartile 1 and quartile 3.
Calculations were performed in the Department of Epidemiology using SAS 9.4 (9). The methodology of the study was based on the textbook by van Belle et al. (10).
Results

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Piśmiennictwo
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otrzymano: 2016-08-04
zaakceptowano do druku: 2016-08-25

Adres do korespondencji:
*Teresa Bączkowska
Department of Transplantation Medicine, Nephrology and Internal Medicine Medical University of Warsaw
ul. Nowogrodzka 59, 02-006 Warszawa
tel. +48 507-121-398
tbaczkowska@wum.edu.pl

Postępy Nauk Medycznych 9/2016
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