A Reassessment of the Importance of Low-Count Bacteriuria in Young Women with Acute Urinary Symptoms

The concept of significant bacteriuria for the diagnosis of urinary tract infections was developed by Kass, Sanford, and others in the mid-1950s [1, 2]. It was based on the notion that the quantitative bacterial count could help distinguish between the presence of bacteria that were multiplying in the urine from those that were passed into the voided urine as contaminants from the urethra or introitus. This concept was supported by the observation that E. coli and other enteric bacteria grew well in human urine and could achieve high densities within 8 to 12 hours. The utility and consistency of the criterion of more than 105 colony-forming units (CFU)/mL for the diagnosis of urinary tract infections has been validated repeatedly [3, 4] and is consistent with mathematical formulas that take into account the growth rate of bacteria in urine and the hydrodynamics of the bladder [5]. After the introduction of the quantitative bacterial count, many investigators found that only about one half of women with symptoms of acute lower urinary tract infection met the criterion of more than 105 CFU/mL [6-11]. Stamm and coworkers [12, 13] noted that the voided urine of most symptomatic women, with bacterial counts in the range of 102) to less than 105 CFU/mL, contained the same microorganisms (E. coli, Staphylococcus saprophyticus, and enteric gram-negative bacteria) that are associated with classic urinary tract infections. They recovered the same organisms from urine obtained by suprapubic aspiration or urethral catheterization, and the symptoms responded to treatment with antimicrobial drugs [14]. In some patients, the suprapubic aspirate was sterile, and the infection was thought to be due to E. coli urethritis [15]. Nonetheless, they recommended that the microbiologic criterion for urinary tract infections be reduced to more than 102 CFU/mL. Our study was designed to determine whether a significant association exists between low-count bacteriuria (>102 to 104 CFU/mL) and acute urinary symptoms in young women and to explore the possibilities that low counts might be caused by dilution of the urine or the inability of the bacteria to grow well in the patients' urine. We were also concerned that a change in the criteria for the diagnosis of urinary tract infections might be confounded by the presence of contaminants in voided urine. Methods Patients The study was done at the gynecology clinic at The Ohio State University student health center between April 1991 and May 1992. The study protocol was reviewed and approved by the institutional review board at The Ohio State University. All nonpregnant women who attended the clinic for any reason were eligible to participate, except for those who had taken an oral or injectable antimicrobial drug in the previous week. During a 2- to 3-hour period each day, the clinic nurse consecutively selected each eligible patient who was able to provide a urine specimen at the time of the clinic visit. Oral informed consent was obtained. Each patient was interviewed using a standardized questionnaire that included demographic information; reason for the visit; current symptoms; recent use of antimicrobial drugs; history of symptoms of cystitis; contraceptive use; date of most recent intercourse; and pregnancies. Refusals were less than 5%. The patients were divided into four categories according to current symptoms. These consisted of those with: 1) urinary symptoms (urinary frequency, urgency, small amount of urine, hematuria or dysuria without fever, flank pain or loin pain); 2) vaginal symptoms (vaginal discharge, itching, swelling, redness, soreness or vulvar burning); 3) urinary and vaginal symptoms (some combination of urinary and vaginal symptoms as described above); and 4) asymptomatic (no urinary or vaginal symptoms). Laboratory Methods Clean-catch midstream urine specimens were obtained using a standardized procedure [4]. Patients were asked to cleanse the inner vulval area with a green soap towelette, to rinse twice by wiping from front to back with moistened gauze pads, and to collect a mid-stream urine specimen while keeping the labia spread. The specimens were cultured as soon as they were obtained by streaking the surface of MacConkey and blood agar plates with 0.01 mL and 0.001 mL loops. Reagent strips (Chemstrip, Boehringer Mannheim, Indianapolis, Indiana) were then dipped into the urine. The specimens were refrigerated and transported to the laboratory within 3 hours of collection. Specific gravity was determined with a refractometer (Hand Protometer, National Instrument Co., Baltimore, Maryland). Creatinine levels were measured at the clinical laboratory of The Ohio State University Hospital. A drop of Kova stain (Hycor Biomedical, Garden Grove, California) was added to an aliquot of urine, and the leukocyte count was determined by hemocytometry. The plates were incubated for 48 hours at 37 C. Counts were done for each morphologically distinct colony. The species were identified using standard microbiologic methods. The following procedure was done to determine whether urine, obtained from each patient, could support growth of low numbers of E. coli that might be present in the specimen. An aliquot, obtained from each of 331 consecutive specimens of urine, was incubated at 37 C. The urine was subcultured on MacConkey agar at 0, 2, 4, and 20 hours of incubation using 0.01 mL and 0.001 mL loops. The plates were incubated for 24 hours at 37 C. Colonies were counted and identified by standard methods. Statistical Analysis The data were processed using the EpiInfo, Version 5.0, software program (Centers for Disease Control and Prevention, Atlanta, Georgia). EpiInfo and EpiStat software programs were used to do chi-square tests and most Fisher exact test calculations. The StatXact software program (Cytel Software Corporation, Cambridge, Massachusetts) was used to do the Fisher exact test for those comparisons in which one or both variables had more than two levels. Regression equations and correlation coefficients were calculated using the EpiInfo program. Analysis for linear trends in proportions was done by the method of Schlesselman [16]. Results Characteristics of the Patients The patients consisted of 639 women among whom 388 were asymptomatic; 83 had urinary symptoms only; 53 had urinary and vaginal symptoms; and 115 had vaginal symptoms only. The demographic characteristics of the four groups of women were similar in regard to age; marital status; pregnancies; use of contraceptives; and time of recent sexual intercourse except for less recent intercourse among women with vaginal symptoms compared with asymptomatic women (P = 0.016). Women with urinary symptoms were slightly younger than asymptomatic control women (22.3 3.7 [SD] years versus 23.6 4.3 years, respectively; P = 0.012) and were more often single (96.4% versus 86.1%; P = 0.009) and, although not statistically different, fewer women had a history of pregnancy (10.8% versus 14.9%, respectively; P > 0.2). They were more likely to previously have had urinary tract infections (73.5% versus 44.8%, respectively; P < 0.001) and to have received antibiotics within 6 weeks before the clinic visit (22.9% versus 9.3%, respectively; P < 0.001). No statistical differences occurred among the groups in contraceptive practices. About two thirds of the 512 sexually active women used oral contraceptives, about one third used condoms, and fewer than 2% used the diaphragm for contraception. Association between Bacterial Species and the Presence of Urinary Symptoms and Pyuria The microorganisms isolated by quantitative culture of the urine of asymptomatic women and those with urinary symptoms only are shown in Table 1. Only E. coli and S. saprophyticus were found more often in patients with urinary tract symptoms (P < 0.001). Other gram-negative enteric bacteria (Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter aerogenes) were found more frequently among women with urinary symptoms, but the numbers were small (P > 0.02). Escherichia coli and S. saprophyticus were more frequently associated with pyuria (>20 leukocytes/mm3) than any of the other microorganisms (P < 0.001) (data not shown). Most microorganisms were isolated in pure culture. Mixed cultures of E. coli with other enteric gram-negative bacteria were observed in five patients and a mixture of E. coli and S. saprophyticus in one patient. All the other bacterial species listed in the Table were recovered more frequently from asymptomatic women. Accordingly, in the remainder of the report, only bacterial counts for E. coli, other enteric bacteria, and S. saprophyticus are shown. Table 1. Association between Symptoms of Urinary Tract Infection and Recovery of Bacterial Species from Urine, by Bacterial Count Association between Bacterial Counts and the Presence of Symptoms of Urinary and Vaginal Infection The distribution of patients according to bacterial counts and symptoms is shown in Table 2. Among the asymptomatic control patients, the frequency of significant bacteriuria (>105 CFU/mL) was 3.1%; low-count bacteriuria (>102 to 104 CFU/mL) was present in 10.2%. In contrast, about one third (32.5%) of women with urinary symptoms had significant bacteriuria, and about one half (45.8%) had low-count bacteriuria. Women with combined urinary and vaginal symptoms were similar to those with urinary symptoms only but had a lower rate of significant and low-count bacteriuria. The distribution of bacterial counts among women with vaginal symptoms did not differ from asymptomatic control women (P > 0.2). The odds ratio of an association between bacteriuria and urinary symptoms increased as the bacterial count increased (P < 0.001) (Table 2). The same association was also noted for women who had urinary and vaginal symptoms (P < 0.001). Table 2. Isolation of Escherichia coli, Other Gram-Negative Enteric Bacteria, and Staphylococcus saprophyticus from the Urine of 639 Femal