Béla Köves

Update on biofilm infections in the urinary tract

PurposeBiofilm infections have a major role in implants or devices placed in the human body. As part of the endourological development, a great variety of foreign bodies have been designed, and with the increasing number of biomaterial devices used in urology, biofilm formation and device infection is an issue of growing importance.MethodsA literature search was performed in the Medline database regarding biofilm formation and the role of biofilms in urogenital infections using the following items in different combinations: “biofilm,” “urinary tract infection,” “bacteriuria,” “catheter,” “stent,” and “encrustation.” The studies were graded using the Oxford Centre for Evidence-based Medicine classification.ResultsThe authors present an update on the mechanism of biofilm formation in the urinary tract with special emphasis on the role of biofilms in lower and upper urinary tract infections, as well as on biofilm formation on foreign bodies, such as catheters, ureteral stents, stones, implants, and artificial urinary sphincters. The authors also summarize the different methods developed to prevent biofilm formation on urinary foreign bodies.ConclusionsSeveral different approaches are being investigated for preventing biofilm formation, and some promising results have been obtained. However, an ideal method has not been developed. Future researches have to aim at identifying effective mechanisms for controlling biofilm formation and to develop antimicrobial agents effective against bacteria in biofilms.

An update on prevention and treatment of catheter-associated urinary tract infections

Purpose of review Catheter-related urinary tract infections (UTIs) are among the most important nosocomial infections. This review summarizes the latest advances in the field of catheter care and the management of catheter-associated UTIs. Recent findings The most efficient methods to prevent catheter-associated UTIs are to avoid unnecessary catheterizations and to remove catheters as soon as possible. The use of different reminder systems and implementation of infection control programs can effectively decrease catheter-associated UTIs, although their introduction can be challenging. There is still no evidence to support the routine use of antimicrobial-impregnated catheters, but the use of hydrophilic-coated catheters for clean intermittent catheterization can effectively reduce infections. Preliminary results with chlorhexidine-coated catheters are promising. In cases of serious catheter-associated UTI in patients with a history of previous antibiotic therapy or healthcare-associated bacteraemia, empirical antibiotic treatment should be initiated with activity against multiresistant uropathogens. Suprapubic catheterization is not superior to urethral catheters in terms of reducing the rate of catheter-related bacteriuria. Summary A technology to prevent catheter-associated UTIs is still not available; however, there are promising results with new approaches such as the use of reminder systems and infection control programs, which can effectively decrease the rate of catheter-associated UTIs. There is evidence supporting the use of hydrophilic coated catheters for clean intermittent catheterization, but an optimal catheter material or coating still has to be developed. Evidence-based catheter management is crucial for every patient in need of a catheter.

Do Escherichia coli strains causing acute cystitis have a distinct virulence repertoire

Bacterial virulence factors influence the site and severity of urinary tract infections. While pyelonephritis-associated molecular traits have been defined, virulence factors specific for acute cystitis strains have not been identified. This study examined the virulence factor repertoire of 247 Escherichia coli strains, prospectively isolated from women with community-acquired acute cystitis. Fim sequences were present in 96% of the isolates, which also expressed Type 1 fimbriae. Curli were detected in 75%, 13% of which formed cellulose. Pap sequences were present in 47%, 27% were papG+, 23% were prsG+ and 42% expressed P fimbriae. TcpC was expressed by 33% of the strains, 32% in a subgroup of patients who only had symptoms of cystitis and 42% in patients with signs of upper urinary tract involvement; most frequently by the papG+/prsG+ subgroup. Strains with the full fim, pap and TcpC and curli virulence profile were more common in cystitis patients with than in patients without upper tract involvement (p < 0.05). The varied virulence profile of E. coli strains causing acute cystitis suggests that diverse bacterial strains, expressing Type 1 fimbriae trigger a convergent host response, involving pathways that give rise to the characteristic symptoms of acute cystitis.

Rare emergence of symptoms during long-term asymptomatic Escherichia coli 83972 carriage without an altered virulence factor repertoire.

PURPOSE Asymptomatic bacteriuria established by intravesical inoculation of Escherichia coli 83972 is protective in patients with recurrent urinary tract infections. In this randomized, controlled crossover study a total of 3 symptomatic urinary tract infection episodes developed in 2 patients while they carried E. coli 83972. We examined whether virulence reacquisition by symptom isolates may account for the switch from asymptomatic bacteriuria to symptomatic urinary tract infection. MATERIALS AND METHODS We used E. coli 83972 re-isolates from 2 patients in a prospective study and from another 2 in whom symptoms developed after study completion. We phylogenetically classified the re-isolates, and identified the genomic restriction patterns and gene expression profiles as well as virulence gene structure and phenotypes. In vivo virulence was examined in the murine urinary tract infection model. RESULTS The fim, pap, foc, hlyA, fyuA, iuc, iroN, kpsMT K5 and malX genotypes of the symptomatic re-isolates remained unchanged. Bacterial gene expression profiles of flagellated symptomatic re-isolates were unique to each host, providing no evidence of common deregulation. Symptomatic isolates did not differ in virulence from the wild-type strain, as defined in the murine urinary tract infection model by persistence, symptoms or innate immune activation. CONCLUSIONS The switch from asymptomatic E. coli 83972 carriage to symptomatic urinary tract infection was not explained by reversion to a functional virulence gene repertoire.

The Global Prevalence of Infections in Urology Study: A Long-Term, Worldwide Surveillance Study on Urological Infections

The Global Prevalence of Infections in Urology (GPIU) study is a worldwide-performed point prevalence study intended to create surveillance data on antibiotic resistance, type of urogenital infections, risk factors and data on antibiotic consumption, specifically in patients at urological departments with healthcare-associated urogenital infections (HAUTI). Investigators registered data through a web-based application (http://gpiu.esiu.org/). Data collection includes the practice and characteristics of the hospital and urology ward. On a certain day in November, each year, all urological patients present in the urological department at 8:00 a.m. are screened for HAUTI encompassing their full hospital course from admission to discharge. Apart from the GPIU main study, several side studies are taking place, dealing with transurethral resection of the prostate, prostate biopsy, as well as urosepsis. The GPIU study has been annually performed since 2003. Eight-hundred fifty-six urology units from 70 countries have participated so far, including 27,542 patients. A proxy for antibiotic consumption is reflected by the application rates used for antibiotic prophylaxis for urological interventions. Resistance rates of most uropathogens against antibiotics were high, especially with a note of multidrug resistance. The severity of HAUTI is also increasing, 25% being urosepsis in recent years.

Benefits and Harms of Treatment of Asymptomatic Bacteriuria: A Systematic Review and Meta-analysis by the European Association of Urology Urological Infection Guidelines Panel

People with asymptomatic bacteriuria (ABU) are often unnecessarily treated with antibiotics risking adverse effects and antimicrobial resistance. We performed a systematic review to determine any benefits and harms of treating ABU in particular patient groups. Relevant databases were searched and eligible trials were assessed for risk-of-bias and Grading of Recommendations, Assessment, Development and Education quality. Where possible, a meta-analysis of extracted data was performed or a narrative synthesis of the evidence was presented. After screening 3626 articles, 50 studies involving 7088 patients were included. Overall, quality of evidence ranged from very low to low. There was no evidence of benefit for patients with no risk factors, patients with diabetes mellitus, postmenopausal women, elderly institutionalised patients, patients with renal transplants, or patients prior to joint replacement, and treatment was harmful for patients with recurrent urinary tract infection (UTI). Treatment of ABU resulted in a lower risk of postoperative UTI after transurethral resection surgery. In pregnant women, we found evidence that treatment of ABU decreased risk of symptomatic UTI, low birthweight, and preterm delivery. ABU should be treated prior to transurethral resection surgery. In addition, current evidence also suggests that ABU treatment is required in pregnant women, although the results of a recent trial have challenged this view. PATIENT SUMMARY We reviewed available scientific studies to see if people with bacteria in their urine but without symptoms of urinary tract infection should be treated with antibiotics to eliminate bacteria. For most people, treatment was not beneficial and may be harmful. Antibiotic treatment did appear to benefit women in pregnancy and those about to undergo urological surgery.

Asymptomatic Bacteriuria in Clinical Urological Practice: Preoperative Control of Bacteriuria and Management of Recurrent UTI.

Asymptomatic bacteriuria (ABU) is a common clinical condition that often leads to unnecessary antimicrobial use. The reduction of antibiotic overuse for ABU is consequently an important issue for antimicrobial stewardship and to reduce the emergence of multidrug resistant strains. There are two issues in everyday urological practice that require special attention: the role of ABU in pre-operative prophylaxis and in women affected by recurrent urinary tract infections (rUTIs). Nowadays, this is the time to think over our practice and change our way of thinking. Here, we aimed to summarize the current literature knowledge in terms of ABU management in patients undergoing urological surgery and in patients with rUTIs. In the last years, the approach to patient with ABU has changed totally. Prior to all surgical procedures that do not enter the urinary tract, ABU is generally not considered as a risk factor, and screening and treatment are not considered necessary. On the other hand, in the case of all procedures entering the urinary tract, ABU should be treated in line with the results of a urine culture obtained before the procedure. In patients affected by rUTIs, ABU can even have a protective role in preventing symptomatic recurrence, particularly when Enterococcus faecalis (E. faecalis) has been isolated.

Spectrum and antibiotic resistance of uropathogens between 2004 and 2015 in a tertiary care hospital in Hungary

Purpose. Surveillance of the bacterial spectrum and antibiotic‐resistance patterns of locally occurring uropathogens is essential to serve as a basis for empirical treatment of urinary tract infections (UTIs), as antibiotic‐resistance rates may vary geographically with significant differences between countries and regions, and with time. Methodology. We retrospectively analysed all urine samples taken in the department of urology in a tertiary care hospital in Hungary from January 2004 to December 2015. Results/Key findings. The five most commonly occurring bacteria were Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, Pseudomonas aeruginosa and Proteus mirabilis. Resistance of Escherichia coli to ciprofloxacin increased significantly from 19 to 25%. Although the resistance of Escherichia coli against cephalosporins showed an increasing trend, it still remained generally low. However, resistance rates of K. pneumoniae to cephalosporins were very high, reaching 60%, due to the high rate of extended‐spectrum‐&bgr;‐lactamase‐positive Klebsiella strains. We observed a significant increase in the rate of carbapenem‐resistant Pseudomonas aeruginosa. Conclusion. Fluoroquinolones cannot be recommended for empirical treatment in our region. Cephalosporins can be a good empirical choice for treating Gram‐negative UTIs, but should be avoided when multi‐drug resistant (MDR) bacteria are suspected. Increases in the rate of carbapenem‐resistant Pseudomonas aeruginosa, and in the general rate of MDR bacteria, are both a very alarming trend. We recommend practising prudent antibiotic policy, preferably using antibiotics with the narrowest possible spectrum.

Urinary Tract Infections in Immunocompromised Patients with Diabetes, Chronic Kidney Disease, and Kidney Transplant

CONTEXT This paper provides a brief overview of urinary tract infections (UTIs) in immunocompromised patients from the perspective of a practicing urologist. OBJECTIVE The primary objective was to provide an update on UTIs in immunocompromised patients. Diabetes mellitus (DM), chronic kidney disease, and kidney transplant (KT) are the most common clinical cases encountered by urologists. Diagnosis, management, and future research needs are summarised. EVIDENCE ACQUISITION We conducted a nonsystematic review of the literature. A comprehensive search of the PubMed database between 1996 and 2016 was performed. EVIDENCE SYNTHESIS Clinical diagnosis of UTIs in immunocompromised patients is challenging. Causative pathogens in DM are slightly different to those in the general population, but without any difference in resistance profiles. Keeping serum glucose under control is the most important preventive measure. The prevalence of UTIs in patients with autosomal dominant polycystic kidney disease (ADPKD) is 21-75%. Lipophilic antibiotics are effective in the treatment of infected cysts, albeit with a trend for lower effectiveness due to increasing resistance rates. UTIs are the most common infections in KT recipients, with a reported rate of 45-72%. Diagnostic challenges exist for both ADPKD and KT patients who develop UTIs. Treatment of UTIs should be tailored according to individual patient characteristics and the severity classification framework suggested by the European Society of Infections in Urology. CONCLUSIONS The underlying pathophysiology of UTIs in immunocompromised patients is not well known, which limits UTI management, including early diagnosis, treatment, and prevention. Future research to identify patients at higher risk of UTIs is necessary. PATIENT SUMMARY In this report we looked at patients with a weakened immune system who are more likely to develop a urine infection. We focused on the patient groups most commonly encountered in a urology setting. We found that these patients have a higher risk of urinary infection, but the signs of infection may be different to those in the general population. Early diagnosis is imperative in this group. Further research on early diagnosis and better individualised management strategies are necessary.

Biofilm and Urogenital Infections

Bacterial adherence and the growth of bacteria on solid surfaces as biofilm are both naturally occurring phenomena. Biofilms can be defined as an accumulation of microorganisms and their extracellular products forming structured communities attached to a surface. Biofilms are able to build up under natural circumstances, for instance on the urothelium or prostate stones and they can also colonize the surfaces of implanted medical devices. Biofilm infections have a major role on temporary and permanent implants or devices placed in the human body. In the process of endourological development a great variety of foreign bodies have been invented besides urethral catheters like ureter, prostatic stents, percutan nephrostomy, penile, testicular implants and artificial urinary sphincters. Many biofilms are quite harmful but others can have a positive impact, namely lining healthy intestine and female genito-urinary tract. Biofilms have significant implications for clinical pharmacology, particularly related to antibiotic resistance, drug adsorption onto and off of devices, and minimum inhibitory concentrations of drugs required for effective therapy.