Aetna considers the analysis of volatile organic compounds in urine to detect bacteriuria experimental and investigational because the clinical effectiveness of this technique has not been established.

Urinary tract infections (UTIs) are a leading cause of morbidity and health care expenditures in persons of all ages.  Individuals at increased risk include sexually active young women, the elderly and those undergoing genitourinary instrumentation or catheterization (Orenstein and Wong, 1999).  The diagnosis of UTI may be made on the basis of clinical signs and symptoms in combination with urinalysis results.  A urinalysis that reveals both bacteriuria and pyuria is considered clinically diagnostic of UTI.  Traditionally, confirmatory cultures have been obtained to verify the infection and identify the specific organism(s) involved; however, this standard is evolving.  If a culture is obtained, the presence of at least 100,000 colony-forming units (CFU) of bacteria on a voided specimen has classically been used as the culture-based definition of UTI.  Lower colony counts (100 CFU or less) may be used to establish a clinical diagnosis in catheterized or aspirated specimens from symptomatic patients (Griebling, 2004).

Research directed towards rapid and early detection of UTI to exclude probable negatives have facilitated the development of sensor technology and the production of devices known as “electronic noses” that can detect and discriminate the production of volatile compounds from microbial infections in situ.  Such qualitative and semi-quantitative approaches could play a significant role in the early diagnosis of microbial diseases.  Using artificial intelligence and web-based knowledge systems, electronic noses might also have a valuable role in monitoring disease epidemiology (Turner and Magan, 2004). 

Aathithan et al (2001) reported on the use of the Osmetech Microbial Analyzer (OMA) (Osmetech plc, Crewe, UK) for the analysis of bacteria in urine.  The OMA is an automated headspace (the volume above the liquid sample) analyzer fitted with four polymer sensors that respond to different volatile organic compounds released from microorganisms in urine.  The OMA technique is based on the principle that volatile compounds from bacteria are released and can then be detected by gas sensors.  The detection of volatile organic compounds in urine by gas-liquid chromatography (GLC) was demonstrated by earlier investigators (Coloe, 1978; Manja and Rao, 1983; Hayward, 1983); however, these methods were only moderately successful in detecting infected and non-infected urine and did not develop into practical diagnostic tools.  The OMA consists of a carousel where sample vials are kept at a constant temperature.  A co-axial needle is automatically inserted through a sample vial septum and nitrogen gas at 50 % relative humidity is introduced above the surface of the urine via the inner lumen of the needle.  The outer needle lumen allows the sample headspace to be delivered across a sensor array for 3 minutes at a flow rate of 60 ml/min.  The sensor is then allowed to recover before humid nitrogen gas is passed over the sensor for a 4-min wash.  The resistance of each of the polymer sensors is measured during the sampling period, and the change from the initial resistance is calculated.  The needle is then removed; the carousel moves the next sample into position, and the process is repeated.  The system is computer-controlled, and data are captured on to a computer hard disk.  The authors compared the effectiveness of the OMA with standard culture results on 534 urine samples.  When bacteriuria was defined as 100,000 CFU/ml, the sensitivity and specificity of the OMA device were reported as 84 % and 88 %, respectively.  When bacteriuria was defined as 10,000 CFU/ml, the sensitivity fell and the specificity rose, 72 % and 89 %, respectively. 

Aathithan and colleagues (2001) concluded that the OMA shows promise as an automated system for the rapid routine screening of urine specimens; however, the following limitations were reported: (i) it was unclear which of the volatile compounds in the headspace the instrument was responding to; therefore, the present sensors may not be optimized for urine analysis; (ii) the detection of volatile compounds is limited by the present array of sensors; therefore, other significant volatile compounds could be missed; (iii) bacterial volatile products could be lost, either by adsorption onto urinary cells or protein or by dissipation during delays between specimen collection and analysis; (iv) some bacterial species may not produce volatile compounds; and (v) processing speed is limited by the need for the sensors to recover after each sample.  The authors reported that clinical trials with more-refined versions of the instrument are in progress.

The Osmetch Microbial Analyserä - Urinary Tract Infection Detector (OMAä-UTI) (Osmetech plc, Crewe, UK) received 510(k) pre-marketing clearance from the U.S. Food and Drug Administration (FDA) in 2001.  The OMA is intended for use by clinical laboratories as an aid to diagnosis UTI.  According to the 510(k) summary, the OMA-UTI was compared to an existing device, the Uriscreenä (Diatech Diagnostics, Inc.), to establish substantial equivalence.  Urine results with the OMA-UTI were compared to standard culture (a positive culture was defined as 100,000 CFU/ml) in 1,038 urine samples.  The sensitivity and specificity of the OMA-UTI were reported as 81.0 % and 83.1 %, respectively.  The FDA determined the performance of the OMA-UTI compared favorably with the Uriscreen, which reported a sensitivity of 95 % and specificity of 73 % when compared to standard culture.  However, the manufacturer was not required to submit to the FDA the evidence of efficacy that is necessary to support a premarket approval application (PMA).

The analysis of volatile organic compounds in urine to detect bacteria is promising (Aathithan et al, 2001; Pavlou et al, 2002); however, there is inadequate evidence of the clinical effectiveness of this technique.  Clinical outcome studies published in the peer-reviewed medical literature are necessary to determine the clinical value of the analysis of volatile organic compounds in urine.