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Clinical management of chlamydia and gonorrhea infection in a county teaching emergency department—concerns in overtreatment, undertreatment, and follow-up treatment success
The Journal of Emergency Medicine, Vol. 25, No. 1, pp. 7–11, 2003 Copyright © 2003 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/03 $–see front matter
doi:10.1016/S0736-4679(03)00131-8
Original Contributions
CLINICAL MANAGEMENT OF CHLAMYDIA AND GONORRHEA INFECTION IN A COUNTY TEACHING EMERGENCY DEPARTMENT—CONCERNS IN OVERTREATMENT, UNDERTREATMENT, AND FOLLOW-UP TREATMENT SUCCESS M. Andrew Levitt,
DO,*
Suzanne Johnson, DO,* Linda Engelstad, Susan Stewart, PhD†
MD,†
Robert Montana,
BA,*
and
*Department of Emergency Medicine and †Division of Primary Care, Department of Internal Medicine, Alameda County Medical Center, Highland Campus, Oakland, California Reprint Address: Dr. M. Andrew Levitt, Department of Emergency Medicine, Alameda County Medical Center, Highland Campus, 1411 E. 31st Street, Oakland, CA 94602
e Abstract—To date, several studies have examined overtreatment or undertreatment of Neisseria gonorrheae, Chlamydia trachomatis, or both in women. However, no study has looked at both subpopulations together, along with eventual treatment of disease-positive patients who were not empirically treated. This study is unique, for it looks at all of these subpopulations to assess overall efficacy of management of these diseases in women. A 1-year prospective, descriptive study was performed in a teaching county hospital Emergency Department (ED). There were 1260 women receiving a pelvic examination and routine GENPROBE testing for gonorrhea and chlamydia who were studied. The main outcome measures were the proportion of women disease positive and initially not treated (undertreated), the proportion of women disease negative who were initially treated (overtreated), as well as the follow-up treatment rate for those undertreated. Finally, the subpopulation of women disease positive and not empirically treated was examined in detail. Of 1260 GEN-PROBEtested women, 81 (6.4%, 95% CI 1.1–11.7%) were disease positive and 31/81 (38.3%, 95% CI 21.2–55.4%) of these women were undertreated. Furthermore, 20/31 (64.5%, 95% CI 43.5– 85.5%) women did not return for follow-up treatment. The billable health care dollars of routine GENPROBE testing per woman (n ⴝ 11/1260, 0.9%) returning for treatment as a result of the test was $4762.80. Four
RECEIVED: 22 February 2002; FINAL ACCEPTED: 29 October 2002
SUBMISSION RECEIVED:
hundred twenty-six (33.8%) of the 1260 women were empirically treated on the initial visit. Of these 426 initially treated women, 376 (88.3%, 95% CI 85.1–91.5%) were GEN-PROBE negative for disease (overtreated). The billable health care dollars of this overtreatment was $12,449.51. This study demonstrates that health care providers are substantially overtreating women who are gonorrhea and chlamydia negative. This generates moral, ethical, health care, and financial concerns. Additionally, onethird of disease-positive women are not treated on initial visit and the majority of undertreated patients are not returning for subsequent treatment. This study provides support for investigating improved methods in the management of chlamydia and gonorrhea in women. © 2003 Elsevier Inc. e Keywords— chlamydia; gonorrhea; sexually transmitted disease
INTRODUCTION In the United States, an estimated 15 million cases of sexually transmitted diseases (STDs) occur each year (1). The two most common bacterial STDs reported are Chlamydia trachomatis and Neisseria gonorrheae (1). It
30 September 2002; 7
8
M. A. Levitt et al.
has been estimated that over 3 million cases of chlamydia and 650,000 cases of gonorrhea occur annually (1). Untreated chlamydia and gonorrhea are major risk factors for Pelvic Inflammatory Disease (PID), which can lead to complications of infertility and tubal pregnancies as well as cost an estimated $7.2 billion a year based on an epidemiological study (2). At the forefront of the difficulty in identifying and treating patients with PID is the difficulty in early diagnosis. The main component of this problem is the indolent nature of the infectious organisms, gonorrhea and especially, chlamydia. In women, chlamydia is often asymptomatic, or it may be associated with common and nonspecific clinical findings (2– 6). As clinicians, we correctly predict PID only 65% of the time (7,8). The poor performance of clinical judgement and lack of a rapid assay test have led to problems of overtreatment and undertreatment of chlamydia and gonorrhea. Various retrospective studies and one prospective study using a population of patients with positive chlamydia or gonorrhea laboratory results determined the rate of undertreatment to be 46 –76% (9 –14). These studies did not address the overtreatment group because disease-negative patients were not studied. Several of these studies determined follow-up of undertreated patients. A range of 17% to 81% did not return for treatment because no contact was attempted, contact was unsuccessful, or contacted patients did not return (9,10,12,15). On the other side of the equation, two of these studies were able to determine, in addition to undertreatment, the rate of overtreatment at the initial Emergency Department (ED) visit to be 78.66%, and 75.00% of treated patients (13,14). However, these two studies did not determine the follow-up success rate to treat the disease-positive untreated patients. To date no study has prospectively examined the entire above-mentioned population to include all women being chlamydia and gonorrhea tested. This would include women empirically treated but disease negative– overtreatment; women not treated but disease positive— undertreatment; and follow-up success for treatment of chlamydia and gonorrhea in the disease-positive initially undertreated group. We designed the present study to assess the efficacy of management of chlamydia and gonorrhea in women.
MATERIALS AND METHODS The study was conducted in the ED of an inner city, county teaching hospital. The emergency services area consists of an Emergency Department (ED) with an annual census of 45,000 patients and an urgent care (UC) area with an annual census of 30,000 patients. The study
protocol was approved by the hospital institutional review board. Women presenting to the ED and UC and receiving a pelvic examination and routine GEN-PROBE testing were eligible for the study. The general policy at this institution is to perform a GEN-PROBE on all women undergoing a pelvic examination. It should be noted that compliance with this policy was not measured. The study population was women specifically receiving a GENPROBE so that the clinical efficacy of our gonorrhea and chlamydia management was assessed. House staff were instructed by senior staff physicians as part of their training on how to use the Gen-Probe. After performance of the GEN-PROBE, empiric treatment for chlamydia or gonorrhea infection was left up to the senior health care provider. The senior health care provider may be one of the 14 attending physicians, 10 senior EM residents, or 11 physician assistants that staff the ED, or 12 attending physicians, 10 senior EM residents, or 5 physician assistants that staff the UC. For purposes of this study, this will be called the gonorrhea/chlamydia management plan. The GEN-PROBE PACE 2 System for Neisseria gonorrhoeae or Chlamydia trachomatis (GEN-PROBE Inc., San Diego, CA) is a DNA probe test that utilizes the technique of nucleic acid hybridization for the detection of female endocervical swab specimens and identification of gonorrhea or chlamydia from culture isolates (16 –21). A data collection instrument was developed for the study to record all of the following. Baseline demographic data were obtained including age, race, and insurance status of all patients. An ongoing list was maintained for patients enrolled in the study. GEN-PROBE results were obtained from the hospital’s laboratory, and the medical record of each patient was reviewed to determine what treatment, if any, was empirically given. If it was determined that the patient had a positive culture and was not empirically treated, an attempt was made to contact the patient. The first contact was done utilizing the telephone number on the record. If this was unsuccessful, a letter was sent to the patient telling her of the infection and the need to get treatment. The patients’ medical records, including Logicare’s Checkout program (Logicare Corporation, Eau Claire, WI) and the medical chart itself, were reviewed for up to 6 months to determine if the patient did eventually seek treatment. This approach would not detect patients who eventually were treated at another medical facility without responding to our communications. To determine the billable health care dollars in the overtreatment group, the amount used for the antibiotics was the average wholesale price plus an institution overhead cost of 4 dollars for oral medication and 7 dollars
Treatment of Chlamydia and Gonorrhea
9
for intramuscular injection. This total amount equaled what was billed by the hospital’s pharmaceutical services. To determine the billable health care dollars of routine GEN-PROBE testing per woman who returned as a result of the test being positive and not having been empirically treated, the amount used for the GENPROBE was the national wholesale price for the kit plus the estimated cost of performing the test, which equaled the amount billed by the hospital’s laboratory services. The population data were entered into SAS (Statistical Analysis Program). The data for the women with a positive test and untreated were entered into Statview (Abacus Concepts, Inc., Berkeley, CA) Categorical data such as overtreatment, undertreatment, and follow-up treatment success, as previously defined, are reported as frequency percent. Continuous level data are reported as mean with standard deviation; 95% confidence intervals are reported for proportions. RESULTS There were 1260 women enrolled in the study. The mean age of the study population was 32.6 ⫾ 10.9 years. Almost half (44%) of the women in the sample were under age 30, and only 8% were over 50. The majority (59%) of the women were African-American, 21% were Hispanic, 9% were Caucasian, and 7% were Asian. Most women (79%) spoke English and the majority of the remainder spoke Spanish. Insurance status was 30.5% unknown, 1% private, 35.0% none, and 33.5% medical assistance. A total of 81 of 1260 women (6.4%, 95% CI 1.1– 11.7%) tested GEN-PROBE-positive for chlamydia, gonorrhea, or both (Table 1). The prevalence of chlamydia and gonorrhea as individual infective organisms were equal but individually three times that of a combined infection. Of the 81 women with positive GENPROBE results, 50 (61.7%, 95% CI 48.2–75.2%) were treated with antibiotics at the initial visit and 31 (38.3%, 95% CI 21.2–55.4%) were not treated (undertreatment) . Four hundred and twenty-six of the 1260 women
Table 2. Summary of Patients Empirically Treated in the ED
GEN-PROBE negative GEN-PROBE positive Total
Number empirically treated
% of the Empirically treated population (n ⫽ 426)
% of the Total population (n ⫽ 1260)
376 50 426
88.26 11.74 100.0
29.84 3.97 33.80
(33.80%) were treated on the initial visit to the ED (Table 2). Three hundred seventy-six (88.3%, 95% CI 85.1–91.5%) patients of initially treated women had negative GEN-PROBE results (overtreatment). The billable health care dollars of this overtreatment was $12,449.51. Only 50 (11.7%, 95% CI 2.8 –20.6%) of initially treated women had positive GEN-PROBE results. Of the 31 initially untreated GEN-PROBE-positive women, 25% were pregnant. All women undergoing a pelvic examination are routinely tested for pregnancy. Twenty-four of these 31 women were RPR tested and 4 were positive. The mean age was 25.1 ⫾ 8 years with a range of 16 –54 years. The majority (68%) of women were African-American, 15% were Hispanic, 10% Caucasian, 4% other, and 3% Asian. Fifteen (48.4%) of these women were able to be contacted. Seven were contacted by phone and eight by letter. Eleven of these patients (73.3% of the contacted patients, 35.48% of the untreated disease-positive patients, 0.87% of the total patient population) returned for treatment. Therefore, 20 women (64.5%, 95% CI, 43.5– 85.5% of the untreated diseasepositive women, 1.59% of the total patient population) did not receive known follow-up care. Mean length of time for return for treatment was 1.4 ⫾ 9.3 days with a range of 3–30 days. The billable health care dollars of the 1260 GENPROBES done for the study population was $52,390.80. Therefore, the billable health care dollars of routine GEN-PROBE testing per woman for the 11 women who returned for treatment as a result of the test was $4762.80.
Table 1. Summary of Disease-Positive Patients
Disease Gonorrhea only Chlamydia only Gonorrhea and Chlamydia Total
Number of GEN-PROBES positive for a particular disease
% of the positive GEN-PROBE population (n ⫽ 81)
% of the Total population (n ⫽ 1260)
36 34
44.4 42.0
2.86 2.70
11 81
13.6 100.0
0.87 6.40
DISCUSSION The Emergency Department often is a primary resource for the diagnosis and treatment of women with STDs and their sequelae. A national survey reported that 47% of all ED gynecologic visits are given a diagnosis of genital tract infection, which includes PID, lower genital tract infections, and STDs. The survey estimated 342,000 ED
10
visits per year for PID, the most common gynecologic diagnosis (22). In our ED and UC, GEN-PROBE testing was to be performed on all women receiving a pelvic examination. This compliance was not measured. The incidence of chlamydia or gonorrhea disease was 6.4%, with roughly an equal distribution between chlamydia (2.86%) and gonorrhea (2.70%). Only 0.87% of the women tested were positive for both chlamydia and gonorrhea. Our incidence of chlamydia and gonorrhea was lower than that reported in retrospective studies of symptomatic women, which have found a 10 –11% prevalence (10,13). Also, asymptomatic screening studies have reported an 8.7–10.4% prevalence of one or both of the infectious organisms (14,23,24). In the present study, initial empiric treatment in the ED was decided by the senior examining health care provider. On initial visit, 33.8% of all tested women received empirical treatment for possible chlamydia or gonorrhea infections. Of these women, the overtreatment rate was 88.26%, i.e., treatment given but patient was GEN-PROBE-negative for both infectious organisms. This level of overtreatment is higher than that reported by Wiest et al. (78.66%) and Mehta et al. (75.00%) (13,14). In our institution, we do tell the patient we are not certain about disease until the culture results are available, nevertheless, overtreatment is an issue of concern from multiple perspectives. From a moral and ethical perspective, incorrectly labeling and treating a woman with an STD may be harmful to that individual. This action may create an unnecessary emotional trauma for the patient secondary to the social stigmas of STDs. This may be increasingly emotionally traumatic for someone in a monogamous relationship, requiring her to inform her partner. Mangione-Smith et al. also voiced the same concern with regard to treating patients who are disease negative (25). A second issue with regard to overtreatment is the risk of bacterial drug resistance developing. Furthermore, treating disease-negative patients unnecessarily exposes them to an increased risk of reactions and side effects from the antibiotics. The health care cost of treating disease patients by the described treatment plan should be of concern. The present study determined a billable health care expense of $12,449.51 secondary to overtreatment and of $4,762.80 per woman who returned due to a positive test and having not been treated. The recommendation of routine gonorrhea and chlamydia testing is understandable due to the clinical difficulty in diagnosing these diseases and the consequences of the diseases going untreated. However, this is costly to the health care system, especially public institutions. For public health agencies to suggest this when the follow-up is poor, but
M. A. Levitt et al.
it will help to monitor disease prevalence, should perhaps be questioned. Perhaps these health care agencies can assume part of the cost if universal testing is to continue (14,26). Thirty-eight percent of the disease-positive women were not empirically treated on the initial visit. Our level of undertreatment is slightly lower then previous published reports (46 –76%) (9 –14). This may be due in part to our higher overtreatment rate compared to other studies. Of the initially untreated disease-positive women, 65% did not return for follow-up treatment. Three previous studies had similar problems with 52– 81% of initially untreated patients not being followed up due to no contact attempt, unsuccessful contact attempts, or refusal by contacted patients to return for treatment (9,10,15). Kelly et al. reported only a 17% follow-up failure rate, reflecting the success of their follow-up program run by and financed by the city health department (12). Our Physician-Assistant-run follow-up program, including a telephone call followed by a letter, was able to contact only 48.4% of these women. Of those contacted, 73% did return for treatment of their STD. It is possible that some of these contacted patients eventually sought treatment elsewhere. It seems that in our ED the failure in follow-up treatment stems more from the program’s unsuccessful contact attempts and less from patients who are aware of having a STD but do not return to the ED. At the time of this study, the GEN-PROBE was one of the more commonly used tests for chlamydia and gonorrhea in EDs. However, it is limited in accuracy. More recently, ligase chain reaction (LCR) testing has been shown to be more sensitive and specific, as well as less costly than past alternatives, including the GEN-PROBE test used in our ED (14,27–33). Moreover, this noninvasive urine-based test is obviously easier because it doesn’t require pelvic examination. However, it still does not supply results in an immediate manner for ED management of chlamydia and gonorrhea. It would have been interesting to look at the diagnostic accuracy rates given the level of training of the health care provider. Future research might study over- and undertreatment rates based on the health care provider type. It was of interest to note that 25% of the untreated GEN-PROBE-positive patients were pregnant. Future research might study this as it relates to fetal morbidity and mortality. Future research might also study undertreatment complications such as PID, infertility, and chronic pelvic pain vs. antibiotic-associated complication rates in the overtreated patients. The authors feel that the findings of this study question whether the present management of chlamydia and gonorrhea in the ED is satisfactory. Overtreatment and
Treatment of Chlamydia and Gonorrhea
the related costs and moral and ethical issues surrounding that; undertreatment and the health care complications and cost of that; and difficulties in follow-up all compound the poor performance of health care providers in treating chlamydia and gonorrhea in women. We have not yet found an efficient and satisfactory method for the diagnosis and treatment of chlamydia and gonorrhea in women in the Emergency Department.
Acknowledgments—This work was supported in part by the National Cancer Institute, Department of Health and Human Services, Grant No. SP01 CA55112.
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18. 19.
20.
REFERENCES 21. 1. Cates W. Estimates of the incidence and prevalence of sexually transmitted diseases in the United States. Sex Transm Dis 1999; 26:S2–S7. 2. Institute of Medicine. The hidden epidemic: confronting sexually transmitted diseases (Committee on Prevention and Control of Sexually Transmitted Diseases). Washington, DC: National Academy Press; 1997. 3. Hook EX, Richey CM, Leone P, et al. Delayed presentations to clinics for sexually transmitted diseases by symptomatic patients. A potential contributor to continuing STD morbidity. Sex Transm Dis 1997;24:443– 8. 4. Hills S, Black C, Newhall J, Walsh C, Groseclose SL. New opportunities for chlamydia prevention: applications of science to the public health practice. Sex Transm Dis 1995;22:197–201. 5. Quinn TC, Gaydos C, Shepherd M, et al. Epidemiologic and microbiologic correlates of Chlamydia trachomatis infection in sexual partnerships. JAMA 1996;276:1737– 42. 6. Jacobson L. Differential diagnosis of acute pelvic inflammatory disease. Am J Obstet Gynecol 1980;138:1006 –11. 7. Selors J, Mahony J, Goldsmith C, et al. The accuracy of clinical findings and laparoscopy in pelvic inflammatory disease. Am J Obstet Gynecol 1991;164:113–20. 8. Hadgu A, Westrom L, Brooks CA, et al. Predicting acute pelvic inflammatory disease: a multivariate analysis. Am J Obstet Gynecol 1986;155:954 – 60. 9. Yealy DM, Greene TJ, Hobbs GD. Underrecognition of cervical Neisseria gonorrhoeae and Chlamydia trachomatis infection in the emergency department. Acad Emerg Med 1997;4:962–7. 10. Kuhn GJ, Campbell A, Merline J, O’Neil BJ. Diagnosis and follow-up of Chlamydia trachomatis infections in the ED. Am J Emerg Med 1998;16:157–9. 11. Chan L, Snyder HS, Verdile VP. A retrospective review of positive Chlamydia cultures in emergency department patients. Am J Emerg Med 1996;14:406 –9. 12. Kelly JJ, Dalsey WC, McComb J, Njuki F. Follow-up program for emergency department patients with gonorrhea or chlamydia. Acad Emerg Med 2000;7:1437–9. 13. Wiest DR, Spear SJ, Bartfield JM. Empiric treatment of gonorrhea and chlamydia in the ED. Am J Emerg Med 2001;19:274 –5. 14. Mehta SD, Rothman RE, Kelen GD, Quinn TC, Zenilman JM. Clinical aspects of diagnosis of gonorrhea and Chlamyida infection in an acute care setting. Clin Infect Dis 2001;32:655–9. 15. Mehta SD, Rothman RE, Kelen GD, Quinn TC, Zenilman JM. Unsuspected gonorrhea and chlamydia in patients of an urban adult
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emergency department: a critical population for STD control intervention. Sex Transm Dis 2001;28:33–9. Cano RJ, Murrieta CM, Spaulding DC, Pascual A. Evaluation of a DNA probe of plasmid origin for detection of chlamydia trachomatis in culture and clinical specimens. Mol Cell Probes 1991;5: 419 –27. Stary A, Kopp W, Zahel B, Nerad S, Teodorowicz L, HortingMuller I. Comparison of DNA-probe test and culture for the detection of Neisseria gonorrhea in genital samples. Sex Transm Dis 1993;20:243–7. Hale YM, Melton ME, Lewis JS, Willis DE. Evaluation of the PACE 2 Neisseria gonorrhoeae assay by three public health laboratories. J Clin Microbiol 1993;31:451–3. Kellogg JA, Seiple JW, Murray CL, Levisky JS. Effect of endocervical specimen quality on detection of Chlamydia trachomatis and on the incidence of false-positive results with the Chlamydiazyme method. J Clin Microbiol 1990;28:1108 –13. Kellogg JA, Seiple JW, Klinedinst JL, Levisky JS. Impact of endocervical specimen quality on apparent prevalence of Chlamydia trachomatis infections diagnosed using an enzyme-linked immunosorbent assay method. Arch Pathol Lab Med 1991;115: 1223–7. Stary A, Kopp W, Zahel B, Muller I, Nerad S, Storch M. Rapid diagnosis of Chlamydia trachomatis with a nucleic acid probe in male and female patients. Dermatology 1994;188:300 – 4. Curtis KM, Hillis SD, Kieke BA Jr, Brett KM, Marchbanks PA, Peterson HB. Visits to emergency departments for gynecologic disorders in the United States, 1992–1994. Obstet Gynecol 1998; 91:1007–12. Jones CA, Knaup RC, Hayes M, Stoner BP. Urine screening for gonococcal and chlamydial infections at community-based organizations in a high-morbidity area. Sex Transm Dis 2000;27:146 – 51. Todd CS, Haase C, Stoner BP. Emergency department screening for asymptomatic sexually transmitted infections. Am J Public Health 2001;91:461– 4. Mangione-Smith R, O’Leary J, McGlynn EA. Health and costbenefits of Chlamydia screening in young women. Sex Transm Dis 1999;26:309 –16. Finelli L, Schillinger JA, Wasserheit JN. Are emergency departments the next frontier for sexually transmitted disease screening? Sex Transm Dis 2001;28:40 –2. Lee H, Chernesky M, Schachter J, et al. Diagnosis of Chlamydia trachomatis genitourinary infection in women by ligase chain reaction assay of urine. Lancet 1995;345:213– 6. Smith K, Ching S, Lee H, et al. Evaluation of ligase chain reaction for use with urine for identification of Neisseria gonorrhoeae in females attending a sexually transmitted disease clinic. J Clin Microbiol 1995;33:455–7. Chernesky MA, Jang D, Lee H, et al. Diagnosis of Chlamydia trachomatis infections in men and women by testing first-void urine by ligase chain reaction. J Clin Microbiol 1994;32:2682–5. Hook EW 3rd, Spitters C, Reichart CA, Neumann TM, Quinn TC. Use of cell culture and rapid diagnostic assay for Chlamydia trachomatis screening. JAMA 1994;272:867–70. Shafer MA, Pantell RH, Schachter AA. Is the rountine pelvic examination needed with the advent of urine-based screening for sexually transmitted diseases? J Arch Pediatr Adolesc Med 1999; 153:119 –25. Xu K, Glanton V, Johnson SR, et al. Dectection of Neisseria gonorrhoeae infection by ligase chain reaction testing of urine among adolescent women with and without Chlamydia trachomatis infection. Sex Transm Dis 1998;25:533– 8. Howell MR, Quinn TC, Gaydos CA. Screening for Chlamydia trachomatis in asymptomatic women attending family planning clinics. A cost-effectiveness analysis of three strategies. Ann Intern Med 1998;128:277– 84.
doi:10.1016/S0736-4679(03)00131-8
Original Contributions
CLINICAL MANAGEMENT OF CHLAMYDIA AND GONORRHEA INFECTION IN A COUNTY TEACHING EMERGENCY DEPARTMENT—CONCERNS IN OVERTREATMENT, UNDERTREATMENT, AND FOLLOW-UP TREATMENT SUCCESS M. Andrew Levitt,
DO,*
Suzanne Johnson, DO,* Linda Engelstad, Susan Stewart, PhD†
MD,†
Robert Montana,
BA,*
and
*Department of Emergency Medicine and †Division of Primary Care, Department of Internal Medicine, Alameda County Medical Center, Highland Campus, Oakland, California Reprint Address: Dr. M. Andrew Levitt, Department of Emergency Medicine, Alameda County Medical Center, Highland Campus, 1411 E. 31st Street, Oakland, CA 94602
e Abstract—To date, several studies have examined overtreatment or undertreatment of Neisseria gonorrheae, Chlamydia trachomatis, or both in women. However, no study has looked at both subpopulations together, along with eventual treatment of disease-positive patients who were not empirically treated. This study is unique, for it looks at all of these subpopulations to assess overall efficacy of management of these diseases in women. A 1-year prospective, descriptive study was performed in a teaching county hospital Emergency Department (ED). There were 1260 women receiving a pelvic examination and routine GENPROBE testing for gonorrhea and chlamydia who were studied. The main outcome measures were the proportion of women disease positive and initially not treated (undertreated), the proportion of women disease negative who were initially treated (overtreated), as well as the follow-up treatment rate for those undertreated. Finally, the subpopulation of women disease positive and not empirically treated was examined in detail. Of 1260 GEN-PROBEtested women, 81 (6.4%, 95% CI 1.1–11.7%) were disease positive and 31/81 (38.3%, 95% CI 21.2–55.4%) of these women were undertreated. Furthermore, 20/31 (64.5%, 95% CI 43.5– 85.5%) women did not return for follow-up treatment. The billable health care dollars of routine GENPROBE testing per woman (n ⴝ 11/1260, 0.9%) returning for treatment as a result of the test was $4762.80. Four
RECEIVED: 22 February 2002; FINAL ACCEPTED: 29 October 2002
SUBMISSION RECEIVED:
hundred twenty-six (33.8%) of the 1260 women were empirically treated on the initial visit. Of these 426 initially treated women, 376 (88.3%, 95% CI 85.1–91.5%) were GEN-PROBE negative for disease (overtreated). The billable health care dollars of this overtreatment was $12,449.51. This study demonstrates that health care providers are substantially overtreating women who are gonorrhea and chlamydia negative. This generates moral, ethical, health care, and financial concerns. Additionally, onethird of disease-positive women are not treated on initial visit and the majority of undertreated patients are not returning for subsequent treatment. This study provides support for investigating improved methods in the management of chlamydia and gonorrhea in women. © 2003 Elsevier Inc. e Keywords— chlamydia; gonorrhea; sexually transmitted disease
INTRODUCTION In the United States, an estimated 15 million cases of sexually transmitted diseases (STDs) occur each year (1). The two most common bacterial STDs reported are Chlamydia trachomatis and Neisseria gonorrheae (1). It
30 September 2002; 7
8
M. A. Levitt et al.
has been estimated that over 3 million cases of chlamydia and 650,000 cases of gonorrhea occur annually (1). Untreated chlamydia and gonorrhea are major risk factors for Pelvic Inflammatory Disease (PID), which can lead to complications of infertility and tubal pregnancies as well as cost an estimated $7.2 billion a year based on an epidemiological study (2). At the forefront of the difficulty in identifying and treating patients with PID is the difficulty in early diagnosis. The main component of this problem is the indolent nature of the infectious organisms, gonorrhea and especially, chlamydia. In women, chlamydia is often asymptomatic, or it may be associated with common and nonspecific clinical findings (2– 6). As clinicians, we correctly predict PID only 65% of the time (7,8). The poor performance of clinical judgement and lack of a rapid assay test have led to problems of overtreatment and undertreatment of chlamydia and gonorrhea. Various retrospective studies and one prospective study using a population of patients with positive chlamydia or gonorrhea laboratory results determined the rate of undertreatment to be 46 –76% (9 –14). These studies did not address the overtreatment group because disease-negative patients were not studied. Several of these studies determined follow-up of undertreated patients. A range of 17% to 81% did not return for treatment because no contact was attempted, contact was unsuccessful, or contacted patients did not return (9,10,12,15). On the other side of the equation, two of these studies were able to determine, in addition to undertreatment, the rate of overtreatment at the initial Emergency Department (ED) visit to be 78.66%, and 75.00% of treated patients (13,14). However, these two studies did not determine the follow-up success rate to treat the disease-positive untreated patients. To date no study has prospectively examined the entire above-mentioned population to include all women being chlamydia and gonorrhea tested. This would include women empirically treated but disease negative– overtreatment; women not treated but disease positive— undertreatment; and follow-up success for treatment of chlamydia and gonorrhea in the disease-positive initially undertreated group. We designed the present study to assess the efficacy of management of chlamydia and gonorrhea in women.
MATERIALS AND METHODS The study was conducted in the ED of an inner city, county teaching hospital. The emergency services area consists of an Emergency Department (ED) with an annual census of 45,000 patients and an urgent care (UC) area with an annual census of 30,000 patients. The study
protocol was approved by the hospital institutional review board. Women presenting to the ED and UC and receiving a pelvic examination and routine GEN-PROBE testing were eligible for the study. The general policy at this institution is to perform a GEN-PROBE on all women undergoing a pelvic examination. It should be noted that compliance with this policy was not measured. The study population was women specifically receiving a GENPROBE so that the clinical efficacy of our gonorrhea and chlamydia management was assessed. House staff were instructed by senior staff physicians as part of their training on how to use the Gen-Probe. After performance of the GEN-PROBE, empiric treatment for chlamydia or gonorrhea infection was left up to the senior health care provider. The senior health care provider may be one of the 14 attending physicians, 10 senior EM residents, or 11 physician assistants that staff the ED, or 12 attending physicians, 10 senior EM residents, or 5 physician assistants that staff the UC. For purposes of this study, this will be called the gonorrhea/chlamydia management plan. The GEN-PROBE PACE 2 System for Neisseria gonorrhoeae or Chlamydia trachomatis (GEN-PROBE Inc., San Diego, CA) is a DNA probe test that utilizes the technique of nucleic acid hybridization for the detection of female endocervical swab specimens and identification of gonorrhea or chlamydia from culture isolates (16 –21). A data collection instrument was developed for the study to record all of the following. Baseline demographic data were obtained including age, race, and insurance status of all patients. An ongoing list was maintained for patients enrolled in the study. GEN-PROBE results were obtained from the hospital’s laboratory, and the medical record of each patient was reviewed to determine what treatment, if any, was empirically given. If it was determined that the patient had a positive culture and was not empirically treated, an attempt was made to contact the patient. The first contact was done utilizing the telephone number on the record. If this was unsuccessful, a letter was sent to the patient telling her of the infection and the need to get treatment. The patients’ medical records, including Logicare’s Checkout program (Logicare Corporation, Eau Claire, WI) and the medical chart itself, were reviewed for up to 6 months to determine if the patient did eventually seek treatment. This approach would not detect patients who eventually were treated at another medical facility without responding to our communications. To determine the billable health care dollars in the overtreatment group, the amount used for the antibiotics was the average wholesale price plus an institution overhead cost of 4 dollars for oral medication and 7 dollars
Treatment of Chlamydia and Gonorrhea
9
for intramuscular injection. This total amount equaled what was billed by the hospital’s pharmaceutical services. To determine the billable health care dollars of routine GEN-PROBE testing per woman who returned as a result of the test being positive and not having been empirically treated, the amount used for the GENPROBE was the national wholesale price for the kit plus the estimated cost of performing the test, which equaled the amount billed by the hospital’s laboratory services. The population data were entered into SAS (Statistical Analysis Program). The data for the women with a positive test and untreated were entered into Statview (Abacus Concepts, Inc., Berkeley, CA) Categorical data such as overtreatment, undertreatment, and follow-up treatment success, as previously defined, are reported as frequency percent. Continuous level data are reported as mean with standard deviation; 95% confidence intervals are reported for proportions. RESULTS There were 1260 women enrolled in the study. The mean age of the study population was 32.6 ⫾ 10.9 years. Almost half (44%) of the women in the sample were under age 30, and only 8% were over 50. The majority (59%) of the women were African-American, 21% were Hispanic, 9% were Caucasian, and 7% were Asian. Most women (79%) spoke English and the majority of the remainder spoke Spanish. Insurance status was 30.5% unknown, 1% private, 35.0% none, and 33.5% medical assistance. A total of 81 of 1260 women (6.4%, 95% CI 1.1– 11.7%) tested GEN-PROBE-positive for chlamydia, gonorrhea, or both (Table 1). The prevalence of chlamydia and gonorrhea as individual infective organisms were equal but individually three times that of a combined infection. Of the 81 women with positive GENPROBE results, 50 (61.7%, 95% CI 48.2–75.2%) were treated with antibiotics at the initial visit and 31 (38.3%, 95% CI 21.2–55.4%) were not treated (undertreatment) . Four hundred and twenty-six of the 1260 women
Table 2. Summary of Patients Empirically Treated in the ED
GEN-PROBE negative GEN-PROBE positive Total
Number empirically treated
% of the Empirically treated population (n ⫽ 426)
% of the Total population (n ⫽ 1260)
376 50 426
88.26 11.74 100.0
29.84 3.97 33.80
(33.80%) were treated on the initial visit to the ED (Table 2). Three hundred seventy-six (88.3%, 95% CI 85.1–91.5%) patients of initially treated women had negative GEN-PROBE results (overtreatment). The billable health care dollars of this overtreatment was $12,449.51. Only 50 (11.7%, 95% CI 2.8 –20.6%) of initially treated women had positive GEN-PROBE results. Of the 31 initially untreated GEN-PROBE-positive women, 25% were pregnant. All women undergoing a pelvic examination are routinely tested for pregnancy. Twenty-four of these 31 women were RPR tested and 4 were positive. The mean age was 25.1 ⫾ 8 years with a range of 16 –54 years. The majority (68%) of women were African-American, 15% were Hispanic, 10% Caucasian, 4% other, and 3% Asian. Fifteen (48.4%) of these women were able to be contacted. Seven were contacted by phone and eight by letter. Eleven of these patients (73.3% of the contacted patients, 35.48% of the untreated disease-positive patients, 0.87% of the total patient population) returned for treatment. Therefore, 20 women (64.5%, 95% CI, 43.5– 85.5% of the untreated diseasepositive women, 1.59% of the total patient population) did not receive known follow-up care. Mean length of time for return for treatment was 1.4 ⫾ 9.3 days with a range of 3–30 days. The billable health care dollars of the 1260 GENPROBES done for the study population was $52,390.80. Therefore, the billable health care dollars of routine GEN-PROBE testing per woman for the 11 women who returned for treatment as a result of the test was $4762.80.
Table 1. Summary of Disease-Positive Patients
Disease Gonorrhea only Chlamydia only Gonorrhea and Chlamydia Total
Number of GEN-PROBES positive for a particular disease
% of the positive GEN-PROBE population (n ⫽ 81)
% of the Total population (n ⫽ 1260)
36 34
44.4 42.0
2.86 2.70
11 81
13.6 100.0
0.87 6.40
DISCUSSION The Emergency Department often is a primary resource for the diagnosis and treatment of women with STDs and their sequelae. A national survey reported that 47% of all ED gynecologic visits are given a diagnosis of genital tract infection, which includes PID, lower genital tract infections, and STDs. The survey estimated 342,000 ED
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visits per year for PID, the most common gynecologic diagnosis (22). In our ED and UC, GEN-PROBE testing was to be performed on all women receiving a pelvic examination. This compliance was not measured. The incidence of chlamydia or gonorrhea disease was 6.4%, with roughly an equal distribution between chlamydia (2.86%) and gonorrhea (2.70%). Only 0.87% of the women tested were positive for both chlamydia and gonorrhea. Our incidence of chlamydia and gonorrhea was lower than that reported in retrospective studies of symptomatic women, which have found a 10 –11% prevalence (10,13). Also, asymptomatic screening studies have reported an 8.7–10.4% prevalence of one or both of the infectious organisms (14,23,24). In the present study, initial empiric treatment in the ED was decided by the senior examining health care provider. On initial visit, 33.8% of all tested women received empirical treatment for possible chlamydia or gonorrhea infections. Of these women, the overtreatment rate was 88.26%, i.e., treatment given but patient was GEN-PROBE-negative for both infectious organisms. This level of overtreatment is higher than that reported by Wiest et al. (78.66%) and Mehta et al. (75.00%) (13,14). In our institution, we do tell the patient we are not certain about disease until the culture results are available, nevertheless, overtreatment is an issue of concern from multiple perspectives. From a moral and ethical perspective, incorrectly labeling and treating a woman with an STD may be harmful to that individual. This action may create an unnecessary emotional trauma for the patient secondary to the social stigmas of STDs. This may be increasingly emotionally traumatic for someone in a monogamous relationship, requiring her to inform her partner. Mangione-Smith et al. also voiced the same concern with regard to treating patients who are disease negative (25). A second issue with regard to overtreatment is the risk of bacterial drug resistance developing. Furthermore, treating disease-negative patients unnecessarily exposes them to an increased risk of reactions and side effects from the antibiotics. The health care cost of treating disease patients by the described treatment plan should be of concern. The present study determined a billable health care expense of $12,449.51 secondary to overtreatment and of $4,762.80 per woman who returned due to a positive test and having not been treated. The recommendation of routine gonorrhea and chlamydia testing is understandable due to the clinical difficulty in diagnosing these diseases and the consequences of the diseases going untreated. However, this is costly to the health care system, especially public institutions. For public health agencies to suggest this when the follow-up is poor, but
M. A. Levitt et al.
it will help to monitor disease prevalence, should perhaps be questioned. Perhaps these health care agencies can assume part of the cost if universal testing is to continue (14,26). Thirty-eight percent of the disease-positive women were not empirically treated on the initial visit. Our level of undertreatment is slightly lower then previous published reports (46 –76%) (9 –14). This may be due in part to our higher overtreatment rate compared to other studies. Of the initially untreated disease-positive women, 65% did not return for follow-up treatment. Three previous studies had similar problems with 52– 81% of initially untreated patients not being followed up due to no contact attempt, unsuccessful contact attempts, or refusal by contacted patients to return for treatment (9,10,15). Kelly et al. reported only a 17% follow-up failure rate, reflecting the success of their follow-up program run by and financed by the city health department (12). Our Physician-Assistant-run follow-up program, including a telephone call followed by a letter, was able to contact only 48.4% of these women. Of those contacted, 73% did return for treatment of their STD. It is possible that some of these contacted patients eventually sought treatment elsewhere. It seems that in our ED the failure in follow-up treatment stems more from the program’s unsuccessful contact attempts and less from patients who are aware of having a STD but do not return to the ED. At the time of this study, the GEN-PROBE was one of the more commonly used tests for chlamydia and gonorrhea in EDs. However, it is limited in accuracy. More recently, ligase chain reaction (LCR) testing has been shown to be more sensitive and specific, as well as less costly than past alternatives, including the GEN-PROBE test used in our ED (14,27–33). Moreover, this noninvasive urine-based test is obviously easier because it doesn’t require pelvic examination. However, it still does not supply results in an immediate manner for ED management of chlamydia and gonorrhea. It would have been interesting to look at the diagnostic accuracy rates given the level of training of the health care provider. Future research might study over- and undertreatment rates based on the health care provider type. It was of interest to note that 25% of the untreated GEN-PROBE-positive patients were pregnant. Future research might study this as it relates to fetal morbidity and mortality. Future research might also study undertreatment complications such as PID, infertility, and chronic pelvic pain vs. antibiotic-associated complication rates in the overtreated patients. The authors feel that the findings of this study question whether the present management of chlamydia and gonorrhea in the ED is satisfactory. Overtreatment and
Treatment of Chlamydia and Gonorrhea
the related costs and moral and ethical issues surrounding that; undertreatment and the health care complications and cost of that; and difficulties in follow-up all compound the poor performance of health care providers in treating chlamydia and gonorrhea in women. We have not yet found an efficient and satisfactory method for the diagnosis and treatment of chlamydia and gonorrhea in women in the Emergency Department.
Acknowledgments—This work was supported in part by the National Cancer Institute, Department of Health and Human Services, Grant No. SP01 CA55112.
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18. 19.
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