UTIs are the most common infections in the early postoperative phase after kidney transplantation. A urinary tract infection can lead to sepsis and be a potential threat to life. The impact of urinary tract infection on the allograft outcome is still under debate. Recent data suggests a negative impact on allograft function of even single episodes of urinary tract infections. In our collective Urinary tract infections were accompanied by worse creatinine clearance at the end of our study period, however the numbers are too be able to deduct a causation. Similar findings have been described by the Mayo Group before.[2] Others did not see a difference in GFR at the baseline but found a decrease in GFR after one year. [22]
With a mean time to urinary tract infection of 10 days after KT in our cohort most urinary tract infections tend to be diagnosed within the second week after transplantation. They appear to be independent of short term perioperative antibiotic prophylaxis. While patients in other countries are discharged from the hospital after 7 to 10 days our mean length of stay was over 20 days. One explanation could be that in the Eurotransplant region and Germany due to serious organ shortage we are forced to transplant more and more marginal organs. This is also apparent in the lower GFR in our collective compared to other cohorts.[22] Thus it is hard to conclude whether urinary tract infections are the cause of or caused by unfavorable graft functions. Others have described no difference in donor criteria between their UTI group and control group. This was evaluated for both predominantly living donor populations as well as predominantly deceased donors.[3, 5, 22] Camargo et al. described to use of UNOS expanded criteria kidneys to be a risk factor.
When patients developed a UTI during their hospital stay, the Double-J- was removed immediately. Surprisingly, early or late removal had no impact on urinary leakage or other ureteral complications, so that the primary need of stenting should be assessed. Liu et al have described a benefit of early stent removal in a randomized trial.[16] Our ongoing practice of removing the stent after 21 days or earlier in infection has been backed by a review by Visser et al who also estimate 21 days post transplant to likely be the ideal time based on current knowledge.[25]
Twenty-three percent of our patients developed asymptomatic bacteriuria in the first month which is comparable to other reports. Most transplant centers treat asymptomatic bacteriuria after KT.[6] As per protocol we treat ASB within the first month post-transplant but other timeframes have been described (e.g. 3 months post-op).[15] A recent meta analysis from Spain recommended not treating longer than within the first month post KT[11], since there are only very limited studies on the diagnosis and treatment of asymptomatic bacteriuria within the first month post transplant.[14] A recent randomized trial has shown that there is no difference in the graft and patient outcome if asymptomatic bacteriurias were not treated. They found no difference in graft function which is according to our own findings.[18] A Cochrane review on the only two available randomized controlled trials (including Origuen et al) also routed against systematic treatment. [7]
While we treated all these patients and thus cannot give more insights into whether to treat or not we want to stress that especially hemodialysis patients (possibly due to lower diuresis) appear to be at an increased risk of developing asymptomatic bacteriuria post transplant. In our study 30% of hemodialysis patients developed asymptomatic bacteriuria compared to only 8% in peritoneal dialysis patients. Randomized trials will be needed to compare withholding antibiotics for asymptomatic bacteriuria in the early phase after KT. The prevalence of asymptomatic bacteriuria appears to be decreasing to about 4% of patients 2 months after KT.[8] Whether further screening is necessary remains to be debated.
In the treatment of asymptomatic bacteriuria there might be a place for the use of Fosfomycin / Pivmecillinam / Nitrofurantoin which are usually not recommended as first line therapy for urinary tract infections in transplant recipients. These agents will grow in popularity given they appear to be safe and efficient even in ESBL bacteria.[17, 23] Furthermore after the recommendation to avoid fluorchinolones in kidney transplant recipients they are also the only valid oral option for outpatient treatment.
Overall we keep treating our patients empirically if they show signs of urinary tract infections. Further data is needed whether it may be safe to wait for the antibiotic resistograms in patients that fulfill he UTI criteria but are not septi(cemi)c, in order to avoid antibiotic exposure to resistant bacteria. When treating empirically the choice of antibiotic must be made with the centers own urinary tract infection’s spectrum and antibiotic resistance in mind, which may vary a lot regionally. Furthermore we saw a different pattern of antibiotic resistance in our Transplant urinary tract infections compared to our overall urinary tract infections. Treatment initiation should also take into account the pattern of laboratory findings.
With regards to perioperative prophylaxis our extended antibiotic protocol has not brought any benefit with regards to urinary tract- and surgical site infections. Similar results have been described by other centers before. A single shot perioperative antibiotic prophylaxis appears to be sufficient. [19] Interestingly, Bachmann et al described 16 different perioperative antibiotic prophylaxis schemes in 65 Eurotransplant KT centers. [4] With regards to the randomized trial and the non-inferiority of a single shot PAP we changed our protocol to a single shot cephalosporin before incision. Furthermore, after two severe PCP infections (one fatal) within the first year post-TX in Basiliximab inducted patients, we changed our PCP protocol and are now prescribing TMP-SMX to each patient for at least three months post-TX regardless of induction therapy. The Mayo group also recommend using TMP-SMX for 6 months post-OP.[3] However Singh et al reported no difference in the incidence of urinary tract infections and asymptomatic bacteriuria in patients that underwent PJP prophylaxis.[21]
When assessing the laboratory alterations an increased white blood count was the most common laboratory finding in our patients. More than 50% of gram negative urinary tract infections showed leukocytosis. About 20% showed CRP increase or urinary nitrite positivity. All complicated urinary tract infections were in the gram-negative group including all septic patients. With gram positive bacteria laboratory findings were even more subtle. Given their inability to reduce nitrate to nitrite we were only able to evaluate WBC, CRP and creatinine increase. An increase in WBC was seen in 40% which was also true for creatinine increase. We did not see any CRP increase. None of these patients was severly ill. To our knowledge neither other studies that presented similar data nor the American Society of Transplantation guidelines take into account laboratory findings.[10]
When evaluating antibiotic susceptibility in your KT patients it is essential to compare them to their own peers rather than the general public. Data from antibiotic stewardship teams (ABS) and hospital hygiene can be helpful but need to be observed critically with a regular update. While our ESBL rate of 13,5% was lower than described by Tekkarismaz, who reported 41% ESBL urinary tract infections in Turkey it was considerably higher than the average of 5% described in a 2017 meta analysis. [1, 22] The global numbers are increasing and varying considerably even within states. Based on our general urinary tract infection data the local ABS recommend Piperacillin-Tazobactam empirically. However with resistant strains in > 15%, Piperacillin-Tazobactam does not appear to be the optimal choice. Thus Carbapenems seems to be the best empiric strategy in urinary tract infections with the potential of early down-stepping.