Further bacteriological evaluation of the TOUL mobile system delivering ultra-clean air over surgical patients and instruments.

Two mobile TOUL-400 units (types 1 and 2) that produce an exponential ultra-clean air flow (EUA) via a mobile screen were evaluated (maximum height from floor to centre of screen: type 1, 1.4m; type 2, 1.6m). Bacterial deposition rates were lowered by >60% (P=0.001) over a table area of 1.7 m (length)x1.0m (width) with the TOUL-400 type 1 unit, and the mean air count at 1.0m from the screen was reduced from 23 to 1.6 colony-forming units (CFU)/m3 in experiments in a room with six air changes/h (ACH). The corresponding reductions were two- to three-fold greater in an operating room (OR) with 16 ACH due to higher bacterial contamination levels in the control experiments. The dramatic but localized reduction of the deposition rate recorded on one 14-cm settle plate (>2376-fold at 0.8m from the screen in the OR) apparently reflected the focus of the EUA. The impact of the TOUL-400 unit was underestimated by almost 100-fold by the air counts of bacteria recorded in parallel at the same sampling point (26.5-fold reduction). During sham coronary angiography and sham hip arthroplasty performed in a room with six ACH, ultra-clean air (<10 CFU/m3) was obtained over the incision area with the TOUL-400 type 2 unit when the EUA was undisturbed (maximum screen-wound distance 1.7 m). In actual coronary angiography (room with six ACH, screen-wound distance 2.0-2.3m) and various surgical procedures in the OR (screen-wound distance 1.4-1.8m), ultra-clean air was obtained at the wound in three of 18 instances, characterized by undisturbed air flow and a maximum distance of 1.8 m. The newly developed TOUL-300 surgical instrument table (1.3-1.7 x 0.6m), equipped at one end with the same EUA unit as the TOUL-400 unit, was evaluated for a room with six ACH and an OR with 16 ACH. It yielded ultra-clean air at 0.8m (1.9 CFU/m3, 96% reduction, P=0.01) and reduced the deposition rate by >60% over most of the table surface. Simplified positioning of the screen or a longer reach, plus a mechanism for precise focusing of the air flow on to the wound area would increase the clinical utility of the TOUL EUA system.

Nationwide spread of Klebsiella oxytoca K55 in Swedish neonatal special care wards.

In a nationwide survey of invasive bacterial infections in Swedish neonates, 36% of Klebsiella spp. were Klebsiella oxytoca serotype K55. This unexpectedly high proportion of K55 infections was due to clusters of infection in neonatal special care wards, and at first seemed attributable to nosocomial spread of a K. oxytoca strain of high virulence. Factors predisposing infants to infection were, however, found irrespective of whether the infecting strain was of serotype K55 or not. Additionally, the prevalence rates of a potential virulence factor, siderophore production, were similar among the two groups of strains. During the same period of time a K. oxytoca K55 with similar biochemical phenotype and drug resistance pattern was found to be spread among the neonates in 12 of 22 neonatal wards in Sweden. The increased proportion of invasive neonatal K. oxytoca K55 infections thus seemed to reflect a high rate of colonization rather than an increased virulence of the K55 strain.

Association between climate and Enterobacter colonization in Swedish neonatal units.

OBJECTIVE: To study risk factors for the highly variable local colonization rates with unrelated Enterobacter species strains previously found in 22 Swedish neonatal units (0% to 32.4% of the infants). PATIENTS AND SETTING: The fecal Enterobacter species carriage rates among 953 infants in the 22 special-care neonatal units were correlated with variables related to the ward (size, crowding, staffing, work load, antibiotic usage, level of care, hygienic precautions), and the hospital (temperature of water supplied, geographical location). RESULTS: The average Enterobacter species carriage rate was highest at seven days of age (17% of the infants) and then declined to 3%. Only location of the hospital in an area with warmer climate according to horticultural zone showed an association with Enterobacter species carriage in multivariate analysis (P = 0.005). CONCLUSION: Although Enterobacter species mainly cause nosocomially acquired infections, the occurrence of the organism in special-care neonatal units seemed to be determined more by extrahospital than by intrahospital factors.

Clonal analysis of Streptococcus pneumoniae nonsusceptible to penicillin at day-care centers with index cases, in a region with low incidence of resistance: emergence of an invasive type 35B clone among carriers.

The nasopharyngeal carriage rate of potential respiratory pathogens was studied in 36 index children with a pneumococci nonsusceptible to penicillin (PNSP), in 595 healthy children, and in 123 personnel at 16 day-care centers (DCCs) with index cases in the Stockholm area, an urban area with a low incidence of antibiotic resistant pneumococci, during the winter of 1997-1998. The spread and clonality of PNSP, Haemophilus influenzae and Moraxella catarrhalis, were studied by analyzing antibiotic susceptibility and serotype, and for PSNP also by using pulsed-field electrophoresis (PFGE) and multilocus sequence typing (MLST). In contrast to the low carriage rate found among the adult contacts (2%), 40% of the children harbored pneumococci, of which 20% were PNSP. Nasopharyngeal colonization decreased with age. The 49 PNSP isolates consisted of 20 clones, of which 10 could be identified in more than one child attending the same or different DCCs. In five DCCs, we observed a spread of PNSP from the index case. A novel PNSP clone of type 35B, found to cause invasive disease in several states in the United States, was found to emerge among several carriers at two DCCs . A high proportion of PNSP isolates were multiresistant to antibiotics (34%), which has implications for treatment regimens, even in a country like Sweden where the proportion of PNSP currently is low (3-4%). One PNSP clone of type 9V found among the carriers, has been shown to cause invasive disease in Sweden as well as in other countries, suggesting that one reason for the occurrence of invasive PNSP clones may be their ability to colonize and spread among healthy carriers. Other internationally spread antibiotic resistant pneumococcal clones found were of types 9V, 19F, and 23F.

Host factors versus virulence-associated bacterial characteristics in neonatal and infantile bacteraemia and meningitis caused by Escherichia coli.

Possession of P fimbriae, virulence-associated O and K antigens, haemolysin and aerobactin production, and susceptibility to 10 antimicrobial agents were studied in 63 Escherichia coli strains isolated from blood or CSF of infants who were grouped according to their clinical characteristics. These isolates were compared with 35 faecal E. coli strains from healthy infants. Individual virulence factors showed a relatively weak association with invasive infection except for P fimbriae in urosepsis and aerobactin production in meningitis. Combinations of factors were generally more predictive for defining virulent clones, particularly in infants defined as being at normal risk of developing septicaemia. Thus, 62% of isolates from such infants had characteristics typical of previously described uropathogenic or meningitis-associated clones of E. coli, compared with 32% of the isolates from high-risk infants (i.e., those defined as being at high risk of developing septicaemia) and only 9% of the faecal isolates (p less than 0.001 and less than 0.05, respectively). Overall, 45% of the episodes of invasive infection were caused by such clones, whereas risk factors (conditions considered to be associated with increased risk of invasive infection) were present in 59% of the infected infants (39% in meningitis and urosepsis, 78% in cryptogenic septicaemia and untreated bacteraemia). The results indicated that bacterial factors played a significant causative role in neonatal meningitis and urosepsis, particularly in normal-risk infants, whereas predisposing host factors contributed greatly to cryptogenic septicaemia and untreated bacteraemia.

Clonality among ampicillin-resistant Enterococcus faecium isolates in Sweden and relationship with ciprofloxacin resistance.

OBJECTIVE: To investigate clonal relationships in a nationwide sample of human Enterococcus faecium isolates. METHODS: Biochemical fingerprinting (PhP (PhenePlate) typing) was used to compare 180 fecal ampicillin-resistant E. faecium (ARE) isolates with 169 matched fecal ampicillin-susceptible E. faecium (ASE) isolates from patients in 23 hospitals, collected in 1998, and to study 39 fecal ARE isolates from non-hospitalized individuals collected in 1998, and five ARE and 29 ASE isolates from the early 1990s. Representative ARE and ASE isolates were subjected to pulsed-field gel electrophoresis (PFGE) analysis of genomic DNA and sequencing of the regions encoding the fluoroquinolone targets of the enzymes GyrA and ParC. RESULTS: Both PhP and PFGE results showed a higher homogeneity among ARE than among ASE isolates (P < 0.001). One PhP type (FMSE1) comprised 73% of the hospital ARE isolates (53% of ARE isolates from non-hospitalized individuals, and four of five ARE isolates from the early 1990s), but only 1% of the ASE isolates. PFGE of the hospital E. faecium isolates revealed that 23 of the 25 ARE isolates and one of the 22 ASE isolates were of one dominating type. High-level resistance to ciprofloxacin (MIC > 16 mg/L) was present in 91% of ARE isolates, whereas only low-level resistance (MIC 4-16 mg/L; 35% of isolates) was found among ASE isolates. One mutation in parC (codon 80) and one of two mutations in gyrA (codons 83 or 87) were detected in all ARE isolates tested with high-level ciprofloxacin resistance, but were lacking in ARE and ASE isolates with low-level ciprofloxacin resistance. CONCLUSION: Most ARE isolates in Sweden were clonally related. High-level ciprofloxacin resistance was found in ARE isolates of PhP type FMSE1 as well as in other PhP types, but never in ASE isolates.

Epidemiology and ecology of enterococci, with special reference to antibiotic resistant strains, in animals, humans and the environment. Example of an ongoing project within the European research programme.

The objectives of the present study are to generate knowledge of the ecology and epidemiology of enterococci in the food chain by studying the following: (1) the population structure (in measures of abundance, number of vancomycin resistant strains, antibiotic resistance patterns, diversity, and stability) among enterococcal populations in different geographical regions and in different links of the food chain (2) possible transmission of strains through the food chain and between hospital environments and the food chain (3) the association between vancomycin resistance and individual strains of enterococci and (4) the diversity of the drug resistance genes in enterococci. So far, 1578 samples have been collected from different countries within the EU (Sweden, Denmark, UK and Spain), and from different habitats (pig farms, carcasses in slaughter houses, soil, manure, water, sewage, and humans). Total and vancomycin resistant enterococcal populations in each sample have been enumerated and more than 12000 isolates have been characterised by phenotyping. Representative isolates are further species identified and characterised by genotyping and MIC determination and from antibiotic resistant isolates the resistance genes are characterised.

Relation between nursing procedures, other local characteristics and transmission of enteric bacteria in neonatal wards.

Faecal colonization patterns were studied in 22 neonatal special care units (N = 953 babies) using a novel method for typing of Escherichia coli, Klebsiella spp. and Enterobacter spp. isolates. Sporadic strains of E. coli (found in only one infant in a ward) were taken to indicate natural colonization, whereas local spread of E. coli strains or colonization with sporadic or spreading strains of Klebsiella spp. and Enterobacter spp. was regarded as abnormal (non-maternal) colonization. All apparent risk factors for abnormal neonatal colonization with enteric bacteria identified were modifiable (ward size, staff work load, antibiotic policy, hygienic precautions). Another encouraging finding was that variables harder to modify (crowding, intensity of care) appeared to be unimportant in influencing neonatal colonization patterns with such bacteria.

Transmission of urinary bacterial strains between patients with indwelling catheters--nursing in the same room and in separate rooms compared.

Despite lack of supporting scientific data it has been suggested that patients with an indwelling urinary catheter (IUC) should be nursed in separate rooms to reduce the risk of cross-infection. We conducted a one-month case-control study of nursing home patients with an IUC and bacteriuria, 20 nursed together pairwise and 20 in separate rooms, by weekly urine cultures and typing of the bacterial isolates. The transmission rate of urinary strains between patients was three times higher within rooms (5/9 possible transmissions) than between rooms (9/53 possible transmissions, P = 0.02). The study thus supported nursing IUC patients in separate rooms.

Inconsistent correlation between aerobic bacterial surface and air counts in operating rooms with ultra clean laminar air flows: proposal of a new bacteriological standard for surface contamination.

The relationship between surface contamination (cfus/m2/h) with particles carrying aerobic bacteria and corresponding air contamination rates (cfus/m3) was evaluated in operating rooms (OR) equipped with ultra clean vertical or horizontal laminar airflow (LAF). For the evaluation we collected data during strictly standardized sham operations using non-woven disposable or cotton clothing. Air contamination in the wound and instrument areas (Casella slit sampler) was related to the surface contamination rate (settle plates) in the same areas and in addition, on the patient chest. Typically, the mean surface counts were 20-70 cfus/m2/h and the air counts 1-2 cfus/m3 in disposable clothing experiments, whilst the use of cotton clothing resulted in higher counts of 100-200 cfus/m2/h (wound P > 0.05, patient P > 0.05, instruments P < 0.01) and 4 cfus/m3 (P < 0.02-0.001). In the vertical LAF, taking both disposable and cotton clothing operations together, the surface and air contamination rates (surface/air ratio SAR) were highly correlated (P = 0.02-0.004) and the ratio varied between 18:1 and 50:1 with a mean for wound air of 36:1. Using only disposable clothing in the vertical LAF, the number of significant correlations was reduced. With cotton clothing experiments in vertical LAF and in the horizontal LAF using disposable clothing, no significant correlation between surface and air contamination was found. The wide variation of SAR values and the inconsistent relationship between surface and air counts indicates that measurement of OR air contamination represents an unhelpful method for assessment of surgical site contamination in LAF units. We propose instead that colony counts on sedimentation plates is a clinically more relevant indicator of bacterial OR contamination in LAF units. In addition to the current bacteriological standard for ultra clean OR air of (< 10 cfus/m3) we suggest a corresponding standard for the surface contamination rate of < 350 cfus/m2/h.

Epidemiology of enteric bacteria in neonatal units--influence of procedures and patient variables.

Among 953 infants in 22 neonatal care units studied, 23% (median value, range 0-78) were found to be faecally colonized with one of 21 distinct nosocomial strains of Escherichia coli, Klebsiella or Enterobacter spp. Lower birth weight was associated with such colonization, particularly with nosocomial phenotypes of E. coli. Caesarean section followed by prolonged incubator care, and hospital stay, were additional factors associated with colonization by such strains of E. coli. Antibiotic therapy of the infant and type of feeding were not found to be associated with acquisition of nosocomial strains of enteric bacteria among neonates.

Survival on skin and surfaces of epidemic and non-epidemic strains of enterobacteria from neonatal special care units.

It has been suggested that increased ability to survive on the hands of hospital staff contributes to transmission of certain strains of Gram-negative bacteria. We tested this hypothesis by comparing the survival on fingertips, glass slides and membrane filters of epidemic (M, major) and matched non-epidemic (S, sporadic) faecal strains of Escherichia coli (n = 13 vs. 13) and Klebsiella spp. (n = 19 vs. 19) found among 1066 neonates in 25 special care units (SCUs). The time to 50% killing at 22 degrees C in air was longer for E. coli than for Klebsiella spp. both on human skin (median 6 vs. 2 min P < 0.001) and glass surfaces (15 vs. 8 min P < 0.001). On the other hand, Klebsiella spp. were superior to E. coli in long-term survival tests on membrane filters expressed as the minimum inoculum still yielding growth after 10 days exposure at 22 degrees C in air (10(5) vs. 10(8) bacteria P < 0.001). Despite a large variation in survival times between individual strains no differences between M strains and S strains were observed in any of the three tests. This indicates that bacterial properties other than survival on surfaces contribute to the increased capacity for transmission of certain strains of enterobacteria in SCUs.

Correlation between surface and air counts of particles carrying aerobic bacteria in operating rooms with turbulent ventilation: an experimental study.

Airborne contamination with bacteria-carrying particles (cfu/m3) and their sedimentation rate (cfu/m2/h) was compared in an operating room (OR) equipped with two turbulent ventilation systems. One was a thermally based system with inlet of cool clean air at the floor level and evacuation of the air at the ceiling by convection (17 air changes/h). The other was a conventional plenum pressure system with air supply at the ceiling and evacuation at the floor level (16 air changes/h). The study was made during rigidly standardised sham operations (N = 20) performed in the same OR by the same six member team wearing non-woven disposable or cotton clothing. Airborne contamination in the wound and instrument areas was related to the surface contamination rate in the same areas and in addition, on the patient chest and in the periphery of the OR. With the exception of the periphery of the OR, the surface and air contamination rates were highly correlated in both ventilation systems (P = 0.02-0.0006, r2 = 0.52-0.79). This was also true particularly when disposable clothing was used while the correlation was weaker in cotton clothing experiments. An equation describing the relation between surface and air counts is given. Typically, the surface counts were numerically 16-fold the air counts, i.e., the number of colonies sedimenting on four 14 cm-diameter agar plates during 1 h will almost equal the number of airborne cfu per m3. We propose, that sedimentation plates represent not only a technically easier method than air sampling but when correctly used, are also the most realistic indicator of airborne bacterial OR contamination in areas critical for surgery.

Influence of age on faecal carriage of P-fimbriated Escherichia coli and other gram-negative bacteria in hospitalized neonates.

The aerobic faecal flora of 953 infants aged over 5 days was studied on discharge from 22 neonatal wards in Swedish hospitals. Klebsiella/enterobacter was isolated from 74% of infants and dominated the aerobic gram-negative flora in 19 wards. Escherichia coli was carried by 42% and showed a slight dominance in two wards. Initially klebsiella/enterobacter dominated the flora but became increasingly mixed with and taken over by E. coli, carriage increasing from 21% in infants discharged after 5-7 days to 57% after 3 weeks or later. Among infants with E. coli, P-fimbriated strains were demonstrated in 23% (range 0-67) and were independent of age. Occasional clustering of such strains was observed in 3/22 wards during the study period. It is postulated that the general and local colonization patterns observed reflect differences between individual strains of E. coli and klebsiella in both their capacity for transmission and their persistence in the newborn gut. The role of P-fimbriae in intestinal colonization of neonates by E. coli was, however, not supported.

Surgical area contamination--comparable bacterial counts using disposable head and mask and helmet aspirator system, but dramatic increase upon omission of head-gear: an experimental study in horizontal laminar air-flow.

The effect of different head coverings on air-borne transmission of bacteria and particles in the surgical area was studied during 30 strictly standardized sham operations performed in a horizontal laminar air flow (LAF) unit. The operating team members wore disposable gowns plus either a non-sterile head covering consisting of a squire type disposable hood and triple laminar face mask, a sterilized helmet aspirator system or no head cover at all. In the wound area both types of head cover resulted in low and comparable air (means of 8 and 4cfu/m(3)) and surface contamination (means of 69 and 126cfu/m(2)/h) rates. Omission of head-gear resulted in a three- to five-fold increase (P > or = 0.01- 0.001), depending on site sampled air contamination rate (mean of 22cfu/m(3)) whereas the bacterial sedimentation rate in the wound area increased about 60-fold ( P > or = 0.0001). A proper head cover minimized the emission of apparently heavy particles that were not removed by the horizontal LAF and contained mainly streptococci, presumably of respiratory tract origin. Dust particle counts revealed no differences between the three experimental situations. No correlation between air and surface contamination rates or between air contamination and air particle counts was found. We conclude that, from a bacteriological point of view, disposable hoods of squire type and face masks are equally as efficient as a helmet aspirator system and both will efficiently contain the substantial emission of bacteria-carrying droplets from the respiratory tract occurring when head cover is omitted. Finally, the use of bacterial air counts to assess surgical site surface contamination in horizontal LAF units must be seriously questioned.

Comparison of AP-PCR typing and PCR-ribotyping for estimation of nosocomial transmission of Clostridium difficile.

We recently attempted to clarify an increased incidence of Clostridium difficile-associated diarrhoea (CDAD) in our hospital by arbitrarily primed polymerase chain reaction (AP-PCR) typing of isolates from 147 consecutive patients collected during a 12 month period (Wullt et al. J Hosp Infect 1999;43:265-273). In the present study we compared the results based on previous AP-PCR data with those based on recent PCR ribotyping of the same isolates and re-analysis of a subset of isolates by AP-PCR typing. The pattern of PCR ribotypes was similar among inpatients and outpatients. A cluster of three closely related PCR ribotypes, related to those of the serogroup H and A8 type strains, dominated and comprised 31% of inpatient and 28% of outpatient C. difficile isolates. The apparent nosocomial transmission rate among inpatients with CDAD was only 9% by AP-PCR typing compared with 18 or 36% by PCR ribotyping depending on the definition used (proportion of patients sharing C. difficile type and ward within two or 12 months). Corresponding rates for all CDAD patients were 5% by AP-PCR and 11 or 21% by PCR ribotyping. Thus, most CDAD patients apparently became ill due to their endogenous strain of C. difficile. Because of the low concordance between the two typing methods the proportion of patients fulfilling the criteria for nosocomial transmission by both methods was only 1%. Re-examination of isolates from patients with recurrences revealed a reproducibility problem with AP-PCR typing. We conclude, that of these two PCR-based options for typing of C. difficile PCR ribotyping offers a superior experimental robustness compared with AP-PCR typing.

The use of colonization rate and epidemic index as tools to illustrate the epidemiology of faecal Enterobacteriaceae strains in Swedish neonatal wards.

The epidemiology of faecal Gram-negative bacteria was studied in 953 infants from 22 neonatal special care wards in Swedish hospitals. Two complementary methods to measure presumed nosocomial transmission of bacterial strains were used: the prevalence rate of major (M) phenotypes (strains that had colonized at least 10% of the infants in a particular ward) and the epidemic index (Ei) (which measures the probability of isolating identical strains from different infants in a ward). About 1500 strains of the most common species (Klebsiella spp., Escherichia coli and Enterobacter cloacae) were typed by the Phene Plate (PhP) biochemical fingerprinting system, and selected Klebsiella isolates were also typed by K antigen serotyping. Klebsiella spp. showed a high propensity to spread (median Ei 0.034, max 0.234), whereas E. coli (median Ei 0.006, max 0.140) and E. cloacae (median Ei 0.0, max 0.012) were more seldom involved in outbreaks. High total Eis in the wards were correlated with high cephalosporin usage (Rs = -0.56, P < 0.05). A total of about 600 biochemical phenotypes of Enterobacteriaceae strains were isolated from the 953 infants. Most of these were found in only one or a few infants, but 24 M phenotypes belonging to Klebsiella spp. (N = 19), E. coli (N = 4) and E. cloacae (N = 1) had colonized altogether 239 (25%) infants. Klebsiella M phenotypes similar or identical to each other and carrying K antigen 55 were isolated from 108 (11%) infants in eight wards, and were thus responsible for 45% of the M phenotype carrier rate in all studied infants. It is suggested that they represent a clone of Klebsiella with a high ability to multiply and spread in hospital environments.

Inefficiency of upward displacement operating theatre ventilation.

A new thermally based ventilation system ('Floormaster') with inlet of cool clean air at floor level, and evacuation at the ceiling of the air warmed by activity in the room (upward displacement ventilation, 17 air changes/h) was compared with a standard positive pressure (plenum) ventilation system with air supply through an inclined perforated screen along one wall at the ceiling and evacuation at floor level (conventional turbulent or mixing system, 16 air changes/h). The study was made during rigidly standardized sham operations (N = 20) performed in the same operating room by a six-member team wearing non-woven disposable or cotton clothing. In general the upward displacement system removed dust particles too small to carry bacteria (0.16-<0.3 microm, 0.001

Efficacy of Metronidazole in experimental Bacteroides fragilis otitis media.

The efficacy of metronidazole in otitis media due to Bacteroides fragilis was evaluated in a guinea pig model. Fifty-nine animals received an injection of 10(8) live B. fragilis bacteria through the tympanic membrane into the right middle ear cavity and metronidazole therapy was started 7 days later. On day 14 after challenge the animals were sacrificed and their middle ears analysed. Intraperitoneal injection of 6 mg metronidazole (about 20 mg per kg) once daily, 6 mg twice daily and 15 mg (50 mg per kg) once daily reduced the incidence of culture positive ears from 13/17 among untreated controls to 7/17 (p = 0.08), 3/10 (p = 0.05) and 2/15 (p = 0.001), respectively. The therapeutic efficacy of metronidazole in experimental otitis media was less than that expected from the concentrations of drug recorded in serum and the drug levels presumed to be achieved in the middle ear effusion.

Optimized urinary microscopy for assessment of bacteriuria in primary care.

Microscopy of wet-stained urinary sediment as an indicator of bacteriuria was evaluated in 418 consecutive primary care visits in a small community. Delivery of morning urine was encouraged and contributed to bladder incubation times of 4 or more hours in 79% of the visits; the overall culture positivity was about 80%. Bacteria or leukocytes alone or together as minimal requirements were suboptimal microscopy criteria for bacteriuria, whereas a minimum of moderate amounts of bacteria or 5 leukocytes per high-power field (x400) as a cutoff point yielded the best diagnostic accuracy. Optimization of urinary sediment microscopy in this way resulted in a desirable high sensitivity (97%) and efficacy (86%) in acutely symptomatic patients, as well as reasonably high efficacy (79%) in other patients, independent of sex or bladder incubation time. The method's simplicity and speed recommend it for use in primary care, particularly in patients with acute symptoms of urinary tract infection.