Interstitial cystitis (IC) is a treatable but essentially incurable chronic condition of the bladder manifested by urinary urgency, frequency, and bladder pain. It is of unknown etiology. Researchers are working to understand the causes of IC and to find effective treatments; however, no compelling evidence for any hypothesized cause is available at this time (Stenchever, 2001; Hanno, 2002).

The diagnosis of IC is primarily one of exclusion, made from the combination of symptoms, cystoscopic findings and bladder biopsies (Hanno, 2002; Selo-Ojeme, 2004). Hanno (2002) recommends a bladder biopsy only if necessary to rule out other disorders that might be suggested by the cystoscopic appearance. Some of the symptoms of IC resemble those of bacterial infection, but medical tests reveal no organisms in the urine of patients with IC and antibiotic therapy is of no therapeutic benefit (Hanno, 2002; Chancellor, 2004).

Using a specific broth culturing method developed by a microbiologist, a team of Virginia medical researchers are investigating a theory that IC is caused by gram-positive bacteria. This view is contrary to the peer-reviewed published literature that IC is of non-bacterial origin. The broth culturing method is based on pure culture technology and requires initial culture of urine specimens in broth culture to allow all microbial strains from the specimens to emerge. By transfer aliquots to appropriate differential media, the etiologic agent can then be isolated for further study and reported to the physician along with the appropriate antibiotic sensitivity pattern (Interstitial Cystitis Information Center website). Results by this team of researchers have not been published.

According to Duncan (1997) and Hanno (2002), attempts to show an infectious etiology for IC have been made for a number of years; however, none of these approaches has provided convincing evidence that micro-organisms or viruses are associated with IC. Thus, there are little data to support the role of an infectious etiology for IC or the use of antibiotics in treatment of IC.

The American Urological Association’s clinical practice guideline on "Diagnosis and treatment of interstitial cystitis/bladder pain syndrome" (Hanno et al, 2011), a review on "Methods and incentives for the early diagnosis of bladder pain syndrome/interstitial cystitis" (Fall and Peeker, 2013), as well as UpToDate reviews on "Pathogenesis, clinical features, and diagnosis of interstitial cystitis/bladder pain syndrome" (Clemens, 2013a) and "Management of interstitial cystitis/bladder pain syndrome" (Clemens, 2013b) do not mention the use of broth culture testing.

Smith et al (2014) noted that surgeons frequently obtain intra-operative cultures at the time of revision total joint arthroplasty. The use of broth or liquid medium before applying the sample to the agar medium may be associated with contamination and false-positive cultures; however, the degree to which this is the case is not known. These investigators calculated the performance characteristics of broth-only cultures (sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]) and characterized the organisms identified in broth to examine if a specific organism showed increased proclivity for true-positive periprosthetic joint infection (PJI). These researchers performed a single-institution retrospective chart review on 257 revision total joint arthroplasties from 2009 through 2010. A total of 190 (74 %) had cultures for review. All culture results, as well as treatment, if any, were documented and patients were followed for a minimum of 1 year for evidence of PJI. Cultures were measured as either positive from the broth only or broth negative. The true diagnosis of infection was determined by the Musculoskeletal Infection Society criteria during the pre-operative work-up or post-operatively at 1 year for purposes of calculating the performance characteristics of the broth-only culture. The sensitivity, specificity, PPV, and NPV were 19 %, 88 %, 13 %, and 92 %, respectively. The most common organism identified was coagulase-negative Staphylococcus (16 of 24 cases, 67 %). Coagulase-negative Staphylococcus was present in all 3 true-positive cases; however, it was also found in 13 of the false-positive cases. The authors concluded that broth-only positive cultures showed poor sensitivity and PPV but good specificity and NPV. The good specificity indicated that it can help to rule in the presence of PJI; however, the poor sensitivity makes broth-only culture an unreliable screening test. The authors recommended that broth-only culture results be carefully scrutinized and decisions on the diagnosis and treatment of infection should be based specifically on the Musculoskeletal Infection Society criteria. This study provided Level 4 evidence.

Moisi and colleagues (2016) stated that prior antibiotic use, contamination, limited blood volume, and processing delays reduce yield of blood cultures for detection of Streptococcus pneumoniae. These researchers performed immune-chromatographic testing (ICT) on broth from incubated blood culture bottles and real-time lytA polymerase chain reaction (PCR) on broth and whole blood and compared findings to blood culture in patients with suspected bacteremia. They selected 383 patients in Mali and 586 patients in Thailand based on their blood culture results: 75 and 31 were positive for pneumococcus, 100 and 162 were positive for other pathogens, and 208 and 403 were blood culture negative, respectively. Immune-chromatographic testing and PCR of blood culture broth were at least 87 % sensitive and 97 % specific compared with blood culture; whole blood PCR was 75 to 88% sensitive and 96 to 100 % specific. Pneumococcal yields in children less than 5 years of age increased from 2.9 % to 10.7 % in Mali with greater than 99 % of additional cases detected by whole blood PCR, and from 0.07 % to 5.1% in Thailand with 2/3 of additional cases identified by ICT. The authors concluded that compared with blood culture, ICT and lytA PCR on cultured broth were highly sensitive and specific but their ability to improve pneumococcal identification varied by site. They stated that further studies of these tools are needed before widespread implementation.

Aydogan and colleagues (2019) noted that to-date studies have not clearly identified infectious agents as an etiological factor for IC. Specific microbiological diagnosis for detecting the pathogen with higher sensitivity in IC may decrease the treatment costs and increase psychosocial health of the patients. These researchers carried out a prospective clinical study in 26 IC patients and 20 controls between April and September 2017. All subjects were asked to give mid-stream urine sample for routine urine cultures. Followed by the negative results, symptomatic 26 patients were evaluated for L-form pathogen existence by extraordinary cultivation methods. Biopsy samples were taken from 19 patients with ulcerative lesions in the bladder while collecting sterile urine samples from all 26 patients. PG broth, 5 % sheep blood agar, EMB, Sabouraud's dextrose, LEM, and GYPA were used. Followed by the 1st day inoculations, all inoculated PG broths were sub-cultured into the same solid media at the 2nd and 10th days in case of any growth after incubation of 24 hours under 35 to 37 °C. The "O'Leary Sant Symptom and Problem Index" score forms were used to examine response to the appropriate treatment for those patients with documented pathogens. Bacterial isolations were yielded from samples of 13 IC patients in PG broth; 8 (61.5 %) P. aeruginosa, 2 (15.4 %) K. pneumoniae, 2 (15.4 %) C. mucifaciens, and 1 (7.7 %) E. faecalis were isolated. Antibiotic susceptibility tests were performed. Somehow, the median symptom index and problem scores of those 13 IC patients were lower after the appropriate antibiotic treatment (p < 0.05). The authors concluded that extraordinary mediums with longer incubation periods may reveal a causative pathogen in the etiology of IC. Moreover, these researchers stated that future culture techniques may have some value, because still some of IC/BPS patients are describing symptomatic relief by a group of antibiotics.

Scope of Policy

This Clinical Policy Bulletin addresses broth culture testing for interstitial cystitis.

Experimental and Investigational

Aetna considers broth culture testing for interstitial cystitis experimental and investigational because there is inadequate evidence of the effectiveness of this test in the diagnosis and management of interstitial cystitis.