Comparison of urine and serum concentrations of interleukin-6 in women with acute pyelonephritis or asymptomatic bacteriuria.

The mucosal and systemic interleukin-6 (IL-6) response to urinary tract infection was analyzed in women with acute pyelonephritis or asymptomatic bacteriuria. Urine and serum samples were obtained at diagnosis and after treatment. IL-6 activity was elevated in urine samples from most bacteriuric women, regardless of the severity of infection. Urinary levels greater than 20 units/mL occurred in 25 of 29 women with acute pyelonephritis and in 36 of 42 women with asymptomatic bacteriuria. Elevated serum IL-6 levels were found mainly in patients with acute pyelonephritis: Levels greater than 20 units/mL occurred in 14 of 28 women with acute pyelonephritis compared with 0 of 28 women with asymptomatic bacteriuria. These results suggest that bacteriuria is accompanied by elevated urinary IL-6 levels and that this IL-6 is locally produced. The spread of IL-6 to the circulation in patients with acute pyelonephritis may contribute to the elevation of fever and C-reactive protein characteristic of the disease.

Interleukin-6 response to deliberate colonization of the human urinary tract with gram-negative bacteria.

Intravesical inoculation of patients with Escherichia coli provided an opportunity to examine the interleukin-6 (IL-6) response to a gram-negative bacterial urinary tract infection in humans. All patients secreted IL-6 as a result of infection. Urinary IL-6 was not continuously secreted but appeared as a series of similar peaks during the first 48 h after infection. There was no significant difference in the ability to trigger IL-6 secretion between isogenic adhering or nonadhering strains, but a threshold concentration of 10(5) bacteria per ml of urine was necessary to fully stimulate IL-6 secretion. There was no detectable increase in IL-6 levels in the serum of the colonized individuals, suggesting mainly local IL-6 production. These results demonstrate that IL-6 is a part of the human mucosal response to gram-negative urinary tract infections.

Pregnancies in women with and without renal scarring after urinary infections in childhood.

OBJECTIVE: To compare the outcome of pregnancy in women with and without renal scarring after childhood urinary infections with that in unmatched controls. DESIGN: Retrospective study of pregnancies in women prospectively followed up from their first recognised urinary infection. SETTING: Tertiary referral centre in Gothenburg. SUBJECTS: 111 Women attending an outpatient clinic for women with urinary infection during 1975-83, of whom 41 (65 pregnancies) were studied (19 women with renal scarring (32), 22 without scarring (33)), and 65 controls (65) randomly selected and matched for parity, age, smoking habits, and date of delivery. MAIN OUTCOME MEASURES: Urinary infections and complications in pregnancy. RESULTS: The incidence of bacteriuria during first pregnancies was significantly greater in women with (9, 47%) and without (6, 27%) renal scarring after childhood urinary infection than in controls (1, 2%) (p less than 0.001, 0.01 respectively). Symptomatic infections were seen only among women with a history of urinary infection: four women with renal scarring (three of whom had vesicoureteric reflux) developed pyelonephritis and three cystitis, and one woman without scarring developed pyelonephritis. Mean blood pressure was higher among women with severe renal scarring than controls (4/11 v 3/44; p less than 0.05) before and during pregnancy. There was no significant difference in the incidence of pre-eclampsia, operative delivery, prematurity, or birth weight. CONCLUSIONS: Women with a history of previous urinary infections had a high incidence of bacteriuria during pregnancy, and those with renal scarring and persistent reflux were prone to develop acute pyelonephritis. The risk of serious complications in pregnancy, however, was not increased in women with severe renal scarring, possibly owing to their continuous clinical supervision.

Bacteriuria in pregnancy. Frequency and risk of acquisition.

A total of 3,254 pregnant women attending two antenatal clinics in Göteborg, Sweden, were screened for bacteriuria. The coverage of the pregnant population in the areas served by the two clinics was estimated to be 88%. Of the women who were registered at the two clinics, 99% took part in at least one screening; 71% were screened during each of the three intervals. The high frequency of screening of the women made it possible to estimate the risk of acquiring bacteriuria during pregnancy. This risk increased with the duration of pregnancy from 0.8% of bacteriuric women in the 12th gestational week to 1.93% at the end of pregnancy. The risk of onset of bacteriuria was highest between the ninth and 17th gestational weeks. The 16th gestational week was the optimal time for a single screening for bacteriuria calculated as the number of bacteriuria-free gestational weeks gained by treatment.

Host response in women with symptomatic urinary tract infection.

The agreement between clinical signs and host response was analysed in 174 women with symptomatic urinary tract infection. C-reactive protein (CRP) confirmed the clinical diagnosis in that 94% of non-pregnant and 91% of pregnant women with acute pyelonephritis had serum levels greater than or equal to 30 mg/l, compared with only 5% of cystitis patients. There was a significant increase in the erythrocyte sedimentation rate (ESR) and reduction of the renal concentrating capacity in patients with acute pyelonephritis, although the overlap with the cystitis group was greater than for CRP. The transient decrease in urine osmolality was unrelated to age, as were CRP, ESR and the total white blood cell count. Pregnant women had higher ESR but lower CRP levels than non-pregnant women with acute pyelonephritis. The renal concentrating capacity was more reduced in those infected with Escherichia coli expressing adhesins specifically recognizing Gal alpha 1----4Gal beta-containing receptors on uroepithelial cells.

Virulence of Escherichia coli in relation to host factors in women with symptomatic urinary tract infection.

The relationship between bacterial characteristics and the severity of urinary tract infection in adults has not been clarified. In this study, Escherichia coli strains (n = 178) were prospectively collected from women with community-acquired urinary tract infection. The isolates were identified by O:K:H serotype and characterized for adherence, hemolysin production, and serum bactericidal resistance. The patients had acute pyelonephritis with or without complicating factors and acute cystitis. Nine serotypes (O1:K1:H7, O1:K1:H-, O2:K1:H-, O4:K12:H1, O7:K1:H-, O9:K34:H-, O16:K1:H6, O16:K1:H-, and O75:K5:H-) comprised 65% of the strains in uncomplicated pyelonephritis, but were significantly less often encountered in complicated pyelonephritis or cystitis. Adherence was the single property most characteristic of the pyelonephritogenic clones. Adhesins specifically recognizing Gal alpha 1----4Gal beta-containing receptors occurred in 80% of strains in uncomplicated pyelonephritis, in 50% of strains in complicated infections, and in 37% of cystitis strains. Hemolysin production and serum resistance did not correlate with any disease pattern. Advanced age did not seem to reduce the selection of virulent E. coli to cause pyelonephritis. These results demonstrate in women a relationship between E. coli virulence and the severity of urinary tract infection analogous to that previously observed in pediatric populations and also illustrate the balance between host resistance and bacterial virulence in the urinary tract.

Virulence factors of Escherichia coli in urinary isolates from pregnant women.

Urinary isolates from 24 pregnant women with acute pyelonephritis and from 37 pregnant women with bacteriuria detected at screening were characterized for O:K:H serotype, electrophoretic type, adherence, hemolysin production, and serum resistance. Between the two diagnostic groups, only three clones were identical. For the remaining isolates, both the identification markers and virulence traits differed significantly. The strains from pregnant women with pyelonephritis did not significantly differ from those from non-pregnant women. Thus, pregnancy was shown not to abolish the difference in virulence between Escherichia coli causing acute pyelonephritis and asymptomatic bacteriuria.

Fever and proximal tubular function in acute pyelonephritis.

The urinary excretion of alpha 1-microglobulin (alpha 1M), beta 2-microglobulin (beta 2M), retinol-binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (NAG) as markers of proximal tubular dysfunction was measured in various forms of urinary tract infections (UTI) and in fever due to non-renal infections. The urinary concentration of these proteins was significantly increased in acute pyelonephritis compared with acute cystitis and asymptomatic bacteriuria. Tubular proteinuria and enzymuria could also be demonstrated in subjects with fever of non-renal origin and corresponded to the findings of pyelonephritis. It is suggested that fever per se is the most likely cause of the tubular proteinuria seen in acute pyelonephritis. In localizing an acute UTI characterization of the urinary protein profile seems to have no advantage over a carefully measured body temperature. The urinary excretion of alpha 1M,beta 2M and RBP were highly correlated, while urinary NAG activity was less correlated to these low-molecular weight proteins. Fibrin degradation product D (FDP-D) was detected in the urines in 60% of the patients with acute pyelonephritis and in one third of those with acute cystitis. The estimation of FDP in urine therefore seems to be of little value in the level diagnosis of UTI.

Zoster immunoglobulin in varicella prophylaxis. A study among high-risk patients.

The efficacy of zoster immunoglobulin (ZIG) in preventing varicella was studied among patients in a high-risk group. 173 non-immune patients were observed after exposure to varicella-zoster (VZ) virus and subsequent administration of ZIG. For 138 patients (80%) no sign of varicella was recorded, 16 patients (9%) had a subclinical infection and 19 patients (11%) developed varicella. 12/19 patients with varicella contracted a very mild disease (less than 20 pocks, negligible fever), 5 got mild or normal disease and 2 children, both with acute lymphatic leukemia, developed more pronounced symptoms. Three patients protected by 0.15 ml ZIG/kg body weight after heavy exposure to VZ virus, were not protected at a second exposure 2 weeks later. In an enlarged study group of high-risk patients where 52 patients receiving ZIG developed varicella, the mean incubation period for 42 patients was 21 days. Leukemic patients were found to have a higher frequency of clinical varicella, more pronounced symptoms and a slightly longer incubation period than other high-risk patients. VZ specific antibody titers were compared for various immunoglobulin preparations and found to be 30 times higher in zoster immunoglobulins than in normal immunoglobulins.

Adhesion, hemagglutination, and virulence of Escherichia coli causing urinary tract infections.

The capacity of 453 Escherichia coli strains to agglutinate erythrocytes and yeast cells and to attach to human urinary tract epithelial cells was tested. The strains were isolated from the urine of patients with acute pyelonephritis, acute cystitis, or asymptomatic bacteriuria and from the stools of healthy school children. Three main patterns of hemagglutination were found: (i) mannose-resistant agglutination of human erythrocytes alone or simultaneously with mannose-sensitive agglutination of guinea pig erythrocytes; (ii) only mannose-sensitive agglutination of guinea pig and other erythrocytes; and (iii) no agglutination. Strains with mannose-resistant agglutination of human erythrocytes alone or in combination with mannose-sensitive hemagglutination attached in high numbers to human urinary tract epithelial cells. Bacteria inducing only mannose-sensitive hemagglutination attached in low numbers, and non-agglutinating strains did not bind to the urinary tract epithelial cells. The bacterial surface antigen(s) mediating mannose-resistant hemagglutination of human erythrocytes and attachment to human urinary tract epithelial cells may be one factor selecting for E. coli from among the fecal flora which infect the urinary tract. The highest proportion of strains with this property was found among acute pyelonephritis isolates (77%), and the lowest proportion of strains with this property was found among normal fecal E. coli (16%).

Frequency of E. coli K antigens in urinary-tract infections in children.

The somatic (O) and casular (K) antigens of Escherichia coli from the urine of patients with acute pyelonephritis, acute cystitis, and asymptomatic bacteriuria, and in the faeces of healthy schoolchildren have been investigated. Typing antisera for sixteen capsular acidic polysaccharide K antigens were used, and five (numbers 1, 2, 3, 12, and 13) accounted for 70% of isolates from patients with acute pyelonephritis. These five K antigens were found to a lesser extent in the three other study groups. Thus, only a few K polysaccharides are associated with virulent properties of E. coli for the upper urinary tract. This finding is similar to the association of only some capsular types of pneumococci, meningococci, and Haemophilus influenzae with invasiveness. The identification of virulence markers for E. coli associated with upper-urinary-tract disease may permit more successful control with reference to preventive immunisation.

Sulphonamides in the treatment of acute Escherichia coli infection of the urinary tract in women. Clinical and ecological effects of sulphasomidine and sulphalene.

28 non-pregnant women were treated with conventional doses of sulphasomidine or sulphalene for acute urinary tract infections caused by Escherichia coli. Both preparations were found to be effective in simple cystitis infection with sulphonamide-sensitive organisms. Also, both were found to exert a selective pressure favouring sulphonamide-resistant E. coli in the faecal flora.

Asymptomatic bacteriuria in schoolgirls. II. Differences in escherichia coli causing asymptomatic bacteriuria.

Three hundred and forty-three E. coli strains isolated from the urine of patients with asymptomatic bacteriuria (ABU), symptomatic cystitis, or pyelonephritis were analysed with regard to O group distribution and sensitivity to the bactericidal effect of normal serum. Strains of O groups 1, 2, 4, 6, 7, 16, 18 and 75 were found in 31.3% in ABU, in 58.7% in cystitis and in 79.8% in pyelonephritis. Spontaneous agglutination was noted in 45.2% of ABU, 6.5% of cystitis and 1.7% of pyelonephritis strains. The strains from patients with ABU were significantly more sensitive to the bactericidal effect of normal serum than were those from patients with symptomatic urinary tract infection. In some patients with untreated ABU, changes in the characteristics of the urinary strains isolated were noted. The strains tended to become spontaneously agglutinating as well as more sensitive to the bactericidal activity of normal serum. The strains found in patients with ABU probably had an altered cell wall compared with those found in patients with symptomatic infections such that they produce fewer symptoms and possibly be less virulent.