Decreased invasive capacity of quinolone-resistant Escherichia coli in patients with urinary tract infections.

Quinolone-resistant (QR) Escherichia coli may have lower invasive capacity than does quinolone-susceptible E. coli. To evaluate this, we prospectively collected data regarding all cases of E. coli invasive urinary tract infections (IUTI) in 669 adults admitted to the Infectious Diseases Unit of our hospital during a 3-year period, as well as 10,950 patients with cystitis or asymptomatic bacteriuria who presented to the outpatient clinic during a 1-year period. QR E. coli was isolated in 20% of patients with cystitis, compared with 8% of those with IUTI (P<.05). The proportion of E. coli isolates that were quinolone resistant was similar in patients with bacteremic and nonbacteremic IUTI. The factors of urinary manipulation and structural abnormalities were independently associated with the presence of quinolone resistance. Old age was the only variable independently associated with blood invasion. QR E. coli is less likely to produce invasive disease (pyelonephritis and prostatitis) than is quinolone-susceptible E. coli. However, once pyelonephritis or prostatitis have developed, there is no difference in the incidence of bacteremia.     

Adherence characteristics to human small intestinal mucosa of Escherichia coli isolated from patients with diarrhea or urinary tract infections

Formalin-fixed human ileal mucosa and formalin-fixed or untreated (native) human urinary bladder mucosa were used to test the adherence ability of Escherichia coli enterotoxigenic (ETEC) or uropathogenic (UPEC) for humans. When grown on colonization factor antigen (CFA) agar for 3 h at 37 degrees C, ETEC with CFA/I or CFA/II pili had typical peritrichous flagella and adhered strongly to human ileal lymphoid follicle and villus epithelium. In contrast, E. coli cells with CFA/I or CFA/II pili and possessing very weak or no motility displayed low levels of adherence to the epithelium. UPEC, which possessed type 1 pili and rarely had flagella, strongly adhered to human urinary bladder mucosa but not to human ileal epithelium. Type 1 pili-possessing E. coli isolated from human feces behaved as did UPEC. Moreover, M cells (microfolds) present in human ileal lymphoid follicle epithelium provided adherence sites for type 1 pili but not for CFA/I or CFA/II pili. These data demonstrate the importance of bacterial motility in efficient in vitro adherence to human ileal epithelia, in contrast to human urinary epithelia, and the adhesin specificity of bacterial adherence to M cell microfolds.     

Pathogenesis of urinary tract infections with normal female anatomy

Recurrent urinary tract infections (UTIs) are common among girls and young women who are healthy and have anatomically normal urinary tracts. These infections are a main source of morbidity and health-care costs in this population. The interaction between specific infecting bacteria and urinary tract epithelium characteristics underlies the pathogenesis of this disease. Several pathogen-related factors predispose people to recurrent UTI, including periurethral bacterial colonisation and Escherichia coli virulence. Host behavioural risk factors include voiding dysfunction, high intercourse frequency, and oral contraceptive and spermicide use. The role of vesicoureteral reflux in recurrent childhood UTI is probably overestimated in the medical literature and is important only in a small group of children with high-grade reflux. Family pedigree analysis suggests a familial genetic predisposition for UTI among young females. Animal models show the multigenic nature of recurrent UTI. Putative candidate genes for the disease include ABH blood groups, interleukin-8 receptor (CXCR1), the human leucocyte antigen locus, toll-like receptors, tumour necrosis factor, and Tamm-Horsfall protein.     

Risk factors and mechanisms of fluoroquinolone resistance in 156 Escherichia coli strains clinically isolated from urinary tract infections

As fluoroquinolone-resistant strains of Escherichia coli emerge, several risk factors for fluoroquinolone resistance have become evident, such as amino acid mutations in the quinolone resistance determining regions (QRDR) of gyrA and parC and previous use of fluoroquinolone. This study investigated risk factors for fluoroquinolone resistance and amino acid mutation in the QRDR in E. coli. We investigated the statistical correlation between each amino acid mutation and resistance to levofloxacin. We examined the minimum inhibitory concentration (MIC) of levofloxacin and the amino acid mutations of gyrA and parC by direct DNA sequence in E. coli clinically isolated from urinary tract infection (UTI) patients. We investigated risk factors for levofloxacin resistance, such as age, sex, and previous use of fluoroquinolone. We found a significant correlation between the number of mutations and resistance to levofloxacin (p < 0.001) and between the presence of underlying urinary tract disease and the presence of mutations (p = 0.004) by multivariate analyses. Three mutations in QRDR were demonstrated to be significantly correlated with levofloxacin resistance. In conclusion, these findings contribute to our understanding of the molecular mechanisms and risk factors for fluoroquinolone resistance.     

Plasmid-identified Staphylococcus saprophyticus isolated from the rectum of patients with urinary tract infections.

Among 15 strains of Staphylococcus saprophyticus of various origin, 13 presented different plasmid patterns, making plasmid identification a useful epidemiological marker. In a consecutive study of 14 young female patients with urinary tract infection caused by S. saprophyticus, 6 patients were simultaneously positive for the same bacterium in the stools. Three paired samples contained the identical plasmid-identified clone of S. saprophyticus indicating that the rectum may be a reservoir of this urinary pathogen.     

Properties of Escherichia coli isolates from urinary tract infections in boys

Fifty-five isolates of Escherichia coli from urine of boys younger than three years of age with urinary tract infection (UTI) were compared with strains from girls of the same age range who had UTI. The frequency of P fimbriae, hemolysin, and type 1C fimbriae, previously described as associated with pyelonephritis (PN) in girls, was also high (76%, 60%, and 31%, respectively) in UTI-associated strains from boys. However, in contrast to isolates from girls, strains from lower UTI in boys did not differ from PN-associated strains regarding these three characteristics. In contrast, aerobactin production was significantly associated with PN compared with lower UTI in both sexes. Serotypes O4 and O6 were overrepresented among all UTI-associated strains from boys and PN-associated strains from girls. This overrepresentation was largely accounted for by three clones, one of which was a new clone identified among the UTI-associated strains from boys.     

The effect of leukemic human serum on normal granulopoiesis.

Acute lymphoblastic leukemia (ALL) in children is often characterized by defective granulopoiesis during initial and relapse stages of the disease, resulting in absolute neutropenia in vivo and in low or absent production of granulocyte-macrophage colonies in vitro. The purpose of this study was to determine if serum from leukemic children with ALL could inhibit normal granulopoiesis. Several concentrations of serum from 12 leukemic patients were mixed with normal bone marrow cells and co-cultured by the double layer agar technique. Also, serum from normal individuals and from ALL patients in remission and relapse was examined for inhibitors. Cultures without serum served as controls. The majority of ALL (initial, relapse and remission) and normal sera either stimulated or had no effect on colony formation. These groups also had similar percentages of inhibitory sera, with the exception of the somewhat higher levels of inhibition found in the remission group. Thus, ALL serum resembled normal serum in its effect on in vitro granulopoiesis at the committed granulocyte-macrophage stem cell level. It is therefore unlikely that inhibition of in vivo granulopoiesis at the committed level by serum inhibitors is responsible for ALL-associated neutropenia.     

Design of clinical trials in patients with urinary tract infections

This overview deals with the optimization of the design of clinical trials in patients with urinary tract infections (UTIs). Despite the fact that UTI is one of the most common types of infection and that the main end-point (elimination or persistence of bacteriuria) is objective and easy to register, the quality of studies performed and published has generally been less than optimal. Problems that should always be addressed in the study protocol are definitions of terms used, for example bacteriuria, level of the infection (cystitis or pyelonephritis), and uncomplicated and complicated infections; dimension of the patient's sample to allow adequate testing of a null hypothesis; procedures before, during and after treatment; methods for analysis of the results.In diesem Überblick wird die Optimierung klinischer Studien bei Harnwegsinfektionen (HWI) dargestellt. Obwohl HWI zu den häufigsten Infektionskrankheiten gehören und der Endpunkt (Eliminierung oder Persistenz der Bakteriurie) objektiv und leicht festzustellen ist, zeigt sich, daß die Qualität der durchgeführten und publizierten Studien im allgemeinen nicht optimal ist. Es ist wichtig, daß in allen Studienprotokollen folgende Gesichtspunkte berücksichtigt werden: Definition der verwendeten Begriffe, z. B. Bakteriurie, Ebene der Infektion (Zystitis oder Pyelonephritis) sowie unkomplizierte und komplizierte Infektion; der Umfang der Patientenstichprobe, um die Nullhypothese ausreichend zu testen; Maßnahmen vor, während und nach der Therapie; Methoden zur Analyse der Ergebnisse.     

The potential impact of biomarker-guided triage decisions for patients with urinary tract infections

Objectives

Current guidelines provide limited evidence as to which patients with urinary tract infection (UTI) require hospitalisation. We evaluated the currently used triage routine and tested whether a set of criteria including biomarkers like proadrenomedullin (proADM) and urea have the potential to improve triage decisions.

Methods

Consecutive adults with UTI presenting to our emergency department (ED) were recruited and followed for 30 days. We defined three virtual triage algorithms, which included either guideline-based clinical criteria, optimised admission proADM or urea levels in addition to a set of clinical criteria. We compared actual treatment sites and observed adverse events based on the physician judgment with the proportion of patients assigned to treatment sites according to the three virtual algorithms. Adverse outcome was defined as transfer to the intensive care unit (ICU), death, recurrence of UTI or rehospitalisation for any reason.

Results

We recruited 127 patients (age 61.8 ± 20.8 years; 73.2 % females) and analysed the data of 123 patients with a final diagnosis of UTI. Of these 123 patients, 27 (22.0 %) were treated as outpatients. Virtual triage based only on clinical signs would have treated only 22 (17.9 %) patients as outpatients, with higher proportions of outpatients equally in both biomarker groups (29.3 %; p = 0.02). There were no significant differences in adverse events between outpatients according to the clinical (4.5 %), proADM (2.8 %) or urea groups (2.8 %). The mean length of stay was 6.6 days, including 2.2 days after reaching medical stability.

Conclusions

Adding biomarkers to clinical criteria has the potential to improve risk-based triage without impairing safety. Current rates of admission and length of stay could be shortened in patients with UTI.     

Bacteriology and ultrastructure of the bladder in patients with urinary tract infections

Tissue obtained by biopsy of the bladder from 33 patients with various urinary tract symptoms was studied by conventional bacteriological techniques and by scanning electron microscopy (SEM). All the patients had recurrent urinary tract symptoms which had not completely responded to antibiotic therapy. Eleven of the patients had greater than or equal to 10(8) colony-forming units (CFU) of bacteria/1 urine; six had between 10(6) and 10(7) CFU/1, and 16 were abacteruric. Bacteria were isolated, however, from the tissue obtained by biopsy from eight of the 16 patients with sterile urine and bacteria were seen on the uro-epithelium in 14 of these patients. By comparison, in all samples of tissue obtained from the 11 patients with greater than or equal to 10(8) CFU/1 of urine bacteria were seen on the uro-epithelium and from nine of these, bacteria were subsequently grown. Fastidious organisms were not isolated from any of the patients. The uro-epithelium of all those studied was also shown to be grossly disrupted with increased disturbance and loss of the epithelial cells when compared with tissue obtained from uninfected patients. The degree of uro-epithelial disturbance was greatest in patients with histories of urinary tract infections lasting more than 4 months. The findings suggest that bacteriological examination of the urine does not always reflect bacterial infection on the bladder surface nor disruption of the uro-epithelium. The changes on the bladder surface may explain the patients' symptoms. In view of the results, a scheme is proposed that explains the development of symptoms in patients with urinary tract and bladder infections.