The integration of laboratory clinical quality into the overall hospital clinical quality program is critical in today’s value-based health care delivery models that place a premium on patient outcomes and cost savings. At Kettering Medical Center, the flagship hospital of Kettering Health Network serving patients throughout the Dayton, Ohio, and northern Cincinnati region, the full-service laboratory performs approximately 1.5 million billed tests annually for the patients staying in the 1526 licensed beds of the medical facility.
In an era in which laboratory information constitutes 70% of the data in an electronic medical record (EMR), laboratories exert a powerful influence on quality metrics, such as length of stay, readmission within 30 days, and downstream resource utilization.1 With this comes considerable responsibility to develop evidence-based laboratory test algorithms that improve these quality metrics for patient and financial outcomes. Kettering Medical Center uses the Plan-Do-Check-Act (PDCA) Lean model for quality improvement with a focus on eliminating waste while maximizing value. Recently, we utilized this methodology to drive a quality improvement project involving the adoption of a comprehensive screening method for sexually transmitted infections (STIs).
A Silent and Complex Problem
The Centers for Disease Control and Prevention (CDC) estimates that approximately 20 million new cases of STIs occur each year in the United States at a cost of $16 billion annually, and that half of these cases occur in individuals 15 to 24 years of age.2 The STI epidemic is largely silent because many patients are asymptomatic while they are actively shedding organisms, which significantly increases transmission. In addition, STIs are challenging to manage because they are often complex infections, involving co-infection with multiple pathogens, including bacteria, viruses, and protozoa. These organisms constitute an ecological pool with a common risk factor—transmission via sex. Failure to identify all organisms infecting a given patient may result in incomplete therapy, which can lead to sustained communicability, the potential extension of infection beyond the genital tract, and, in pregnant patients, possible transmission to un- or newborn children.
Furthermore, having one STI places patients at risk for other STIs. For example, the CDC reports that individuals who are infected with sexually transmitted diseases (STDs) are at least two to five times more likely than uninfected individuals to acquire HIV infection if they are exposed to the virus through sexual contact.3 Similarly, infection with herpes simplex virus (HSV) or Trichomonas vaginalis (a protozoan parasite that causes trichomoniasis) prolongs shedding of human papillomavirus (HPV).
Given these factors, it is logical that the complexity of this ecological pool results in a high probability of patients being infected with more than one pathogen. However, many STI pathogens receive little attention because requirements for public health reporting do not exist for many of them, prevalence is poorly understood, and the impact of intervention is largely unknown. Evidence to support the importance of lesser-known pathogens, such as T. vaginalis, mycoplasma, and ureaplasma, and to support the probability that most STIs are mixed in etiology, is wanting because testing technology has lacked both sensitivity and practicality for general use.
Recently, the CDC released updated guidelines for laboratories regarding the detection of Chlamydia trachomatis and Neisseria gonorrhoeae.4 These guidelines clearly state that nucleic acid amplification tests (NAATs) are recommended for detection of genital tract infections in men and women with and without symptoms. The guidelines review commercially available assays for N. gonorrhoeae and C. trachomatis, but do not include any FDA-cleared assays for other STI pathogens, such as HSV 1 and 2, and T. vaginalis. The lack of available FDA-cleared multiplex STI assays is problematic and contributes to the challenge of developing evidence for routine testing beyond that for gonorrhea and chlamydia.
Evaluating a Comprehensive Screening Panel
At Kettering Medical Center, we identified room for improvement in our process of evaluating patients presenting to our ED with a complaint of pelvic pain. Previously, two problems existed: overuse of resources (ie, imaging) and patients making multiple visits for recurrent symptoms. These circumstances raised the question of whether common STI pathogens were being missed in the workup for a single patient during a single encounter.
To address the issue, we introduced a PCR-based STD test panel in our lab. The panel simultaneously tests for N. gonorrhoeae, C. trachomatis, HSV 1 and 2, and T. vaginalis using either genital or urine specimens. We performed an initial clinical validation study involving 20 symptomatic female patients presenting to the ED.
The results from the initial 20 patients tested were game changing. Three patients were positive for N. gonorrhoeae, despite having negative cultures, and six were positive for C. trachomatis. In addition, the panel detected T. vaginalis in six patients, HSV 2 in six patients, and HSV 1 in one patient (also positive for HSV 1 in oral lesions). Four of the total patients had multiple recent prior visits. None of the HSV patients had obvious genital lesions. Three of the women with HSV were previously misdiagnosed as having urinary tract infections on the basis of symptoms of dysuria and pyuria; one of those three was 26 weeks pregnant.
Interestingly, four patients had evidence of bacterial vaginosis based on microscopic criteria. This raised the question of whether microscopic evidence of bacterial vaginosis, in the context of a culture positive for organisms, such as Gardnerella vaginalis, can be misleading and may mask STI pathogens leading to inappropriate therapy, prolonged illness, and prolonged communicability. The alteration in vaginal flora related to an STI and concurrent bacterial vaginosis is not well understood and represents another reason why comprehensive testing for STI pathogens is important if we are to gain an understanding of the pathogenesis of genital infections, particularly in the female patient.
Following the initial clinical validation, the test was implemented for routine use. Clinical performance was subsequently measured in 1855 patients seen between March and August of 2013 in the ED, the women’s health center, and urgent care. Results of all 1855 patients tested by both the comprehensive panel and conventional technology (ie, culture and wet mount) are summarized as follows:
Results of the 1855 patients tested are summarized in TABLES 1 and 2. TABLE 3 depicts the comparison of positive results by method and pathogen.
The data suggest that multiple cases of HSV 1 and 2 and trichomoniasis, as well as co-infections, can go undetected using currently available FDA-cleared NAATs, and that wet mount for trichomoniasis is unreliable. In this series of patients, the positive predictive value of traditional wet mount to the comprehensive STD panel was 98.6%, but the negative predictive value was 51.5%. The burden of trichomoniasis and the substantial evidence linking it to adverse health outcomes, including pelvic inflammatory disease, preterm delivery, cervical cancer, and increased susceptibility to HIV, speaks to the appropriateness of its inclusion in routine screening.
The patients diagnosed as having HSV via the STD panel had no visible lesions and had been misdiagnosed in the past as having urinary tract infections because they had symptoms of dysuria and pyuria. Primary infection with HSV was detected in two such patients, both pregnant, one with documented HSV 2 encephalitis. Genital herpes is a chronic, lifelong infection with nearly continuous, low-level viral shedding and intermittent clinical recurrence. Prompt identification with appropriate laboratory testing is one of the best ways to mitigate the health risks associated with HSV and reduce transmission. The absence of effective laboratory diagnostics inevitably leads to significant downstream testing, repeat visits, and increased morbidity.
Looking to the Future
The goal of reducing the incidence of STIs can only be accomplished if the rates of misdiagnosis and missed diagnoses decrease. Considerable overlap exists in the symptoms and signs for many genital infections, and clinical diagnosis alone is unreliable. Although contemporary NAATs are available to detect both N. gonorrhoeae and C. trachomatis, few are available that detect additional pathogens. Robust multiplex technology can reveal many of the important pathogens causing STIs, resulting in improved patient outcomes, evidence-based therapies, and reduced costs. The next step in the PDCA cycle of continuous improvement is to investigate the role of important emerging pathogens, such as Mycoplasma genitalium.
The author would like to acknowledge the work and technical leadership of the following staff: Karen Wolters, MLS(ASCP), MB(ASCP); Bobbye Owens, MLS(ASCP); Krista Snapp, MLS(ASCP); and Susan Troutman, MT(ASCP).
Carol R. Quinter, PhD, is the director of microbiology and molecular technology at the Kettering Medical Center, Kettering Health Network in Dayton, Ohio. She received her training at the Ohio State University’s departments of microbiology, clinical microbiology, pathology, and medicine.
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