Article, Infectious Diseases

Gonorrhea and chlamydia in the emergency department: Continued need for more focused treatment for men, women and pregnant women

a b s t r a c t

Introduction: Delay in current nucleic acid amplification testing for Neisseria gonorrhoeae and Chlamydia trachomatis has led to recommendations for presumptive treatment in patients with concern for infection and unreliable follow-up. In the urban setting, it is assumed that many patients have unreliable follow-up, therefore presumptive therapy is thought to be used frequently. We sought to measure the frequency of disease and accu- racy of presumptive treatment for these infections.

Methods: This was an observational cohort study performed at an urban academic Level 1 trauma center ED with an annual census of 95,000 visits per year. Testing was performed using the APTIMA Unisex swab assay (Gen- Probe Incorporated, San Diego, CA). Presumptive therapy was defined as receiving treatment for both infections during the initial encounter without confirmation of diagnosis.

Results: A total of 1162 patients enrolled. Infection was present in 26% of men, 14% of all women and 11% of preg- nant women. Despite high frequency of presumptive treatment, N 4% of infected patients in each category went untreated.

Conclusion: Inaccuracy of presumptive treatment was common for these sexually transmitted infections. There is an opportunity to improve diagnostic accuracy for treatment.

(C) 2017

Introduction

Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are two common sexually transmitted infections and the leading preventable causes of infertility, Ectopic pregnancy and Pelvic inflammatory disease [1-3]. The Centers for Disease Control and Prevention (CDC) have estimated that there are nearly 2 million new cases of these sexually transmitted infections nationally each year [3]. The inaccuracy of the history, physical exam and time delay with diagnostic testing has made it impossible to confirm these infections during the initial emer- gency department (ED) visit.

As such, the CDC has recommended presumptive treatment be con- sidered in patients for whom there is concern for a sexually transmitted infection (STI) and unreliable outpatient follow-up [4]. In the urban set- ting, such a scenario is common, and subsequent presumptive therapy is frequently inaccurate [5-10]. For instance, in a pilot study, we had pre- viously estimated that up to 4% of patients presenting to the urban ED are left untreated, despite overtreatment rates exceeding 33% [10].

* Corresponding author at: Kaiser Permanente, Dept. of Emergency Medicine, 3440 E La Palma Ave, Anaheim, CA 92806, United States.

E-mail address: [email protected] (S.P. Wilson).

We sought to further quantify this phenomenon by measuring the frequency of disease, and accuracy of presumptive treatment for men, women and pregnant women in an urban ED.

Methods

Study design

This was an observational cohort study that was performed in parallel to a separate, prospective non-inferiority trial that sought to compare two U.S. Food and Drug Administration approved diagnostic assays for CT and NG in the urban ED. This study was approved by the study site institutional review board with a waived consent and the original non-inferiority trial was registered on Clinicaltrials.gov (NCT02386514).

Study setting and participants

The study was conducted between April 2015 and March 2016 at an urban academic Level 1 trauma center ED with an annual census of ap- proximately 95,000 patient visits per year. All patients of any age who

http://dx.doi.org/10.1016/j.ajem.2017.01.002

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702 S.P. Wilson et al. / American Journal of Emergency Medicine 35 (2017) 701703

underwent NAAT testing for both CT and NG by cervical or urethral swab collection using the APTIMA Unisex assay (Gen-Probe Incorporat- ed, San Diego, CA) were eligible for inclusion. The determination to per- form testing was at the discretion of the treating clinician. As part of our original non-inferiority study, we excluded patients that did not provide a urine specimen during their ED visit or if the research associate was not able to run their Urine sample within 24 h of the initial visit, as this increased risk of degradation of the sample in our non-inferiority trial.

Table 1

Study participant characteristics.

% (n)

Sex

Male

4% (50)

Female

96% (1112)

Race

Black

85% (995)

Hispanic

4% (49)

Caucasian

4% (50)

Unclassified

6% (66)

History

Asymptomatic

4% (42)

Pregnant

30% (338)

Prior STI

26% (300)

Study protocol

Data collection was performed by 3 different paid research associ- ates who were present daily from 8 A.M. – midnight. Research associates did not need to be present during the initial patient visit, just as long as they were able to run sample from the non-inferiority trial within 24 h of visit. These research associates used the electronic medical record (Epic Systems, Verona, WI) to obtain NAAT results, demographic and clinical information through chart abstraction for each patient. The re- search associates received standardized training for determining poten- tial symptoms prior to data abstraction. Presence of symptoms was defined as having report of dysuria or urethral/vaginal discharge and in women, presence of cervicitis or uterine tenderness on exam.

Presumptive treatment was defined by the treating team adminis- tering antibiotics for both infections without having laboratory confir- mation. Treatment was considered accurate if the treating team administered antibiotics for NG and/or CT and the patient tested posi- tive for either infection. Overtreatment was defined by ED treatment followed by negative testing for NG and CT. Missed treatment was de- fined as being positive for either infection, yet not having received treat- ment during the initial encounter. We did not follow patients beyond the ED encounter to determine if those with missed treatment had sub- sequent follow-up for treatment.

Data analysis

All continuous data are presented as mean and standard deviation, while categorical data are presented as count and percentage. Chi- square and Fisher’s exact tests are used to compare presumptive treat- ment rates between those infected and not infected with CT and NG. Statistical significance is set at p b 0.05. All analyses are performed using SAS 9.4 (SAS Institute Inc., Cary, NC, USA).

Results

Eleven-hundred-sixty-two patients were enrolled. Average age was 26 years, 1112 (96%) were female, of which 338 (30%) were pregnant. Three-hundred (26%) patients reported a history of prior STI. Five- hundred-twelve (44%) patients received presumptive treatment. Com- plete study participant characteristics are outlined in Table 1.

Overall, 4% (n = 52) of patients tested positive for NG and 12% (n = 135) tested positive for CT. In men, 8% (n = 4) tested positive for NG and 20% (n = 10) tested positive for CT. In women, 4% (n = 48) tested positive for NG and 11% (n = 125) tested positive for CT. In pregnant woman, 1% (n = 4) tested positive for NG and 8% (n = 34) tested pos- itive for CT. Co-infection with both NG and CT occurred in 3% (n = 1) of men, 2% (n = 22) of women and 1% (n = 3) of pregnant women. Infec- tion rates by sex and pregnancy status are listed in Table 2.

In men, 84% (n = 42) received presumptive treatment, of which 9% (n = 4) tested positive for NG and 19% (n = 8) tested positive for CT. Hence, unnecessary treatment rates were 76% (n = 38) for NG and 68% (n = 34) for CT. There were no missED treatments for NG, but 4% (n = 2) missed treatments for CT. In women, 42% (n = 470) received presumptive treatment, of which 8% (n = 39) tested positive for NG and 17% (n = 78) tested positive for CT. Hence, 38% (n = 431) of women received unnecessary treatment for NG and 35% (n = 392) for

Infection detected

Gonorrhea 4% (52)

Chlamydia 12% (135)

Presumptive treatment

All treated

44% (512)

Men

84% (42)

Women

42% (470)

Pregnant women

17% (58)

CT. There were 1% (n = 9) missed treatments for NG and 4% (n = 47) missed treatments for CT.

In pregnant woman, 17% (n = 58) received presumptive treatment, of which 7% (n = 4) tested positive for NG and 19% (n = 11) tested pos- itive for CT; there were no missed treatments for NG, but 8% (n = 23) missed treatments for CT. Complete presumptive treatment rates by sex and pregnancy status are presented in Table 3.

Discussion

This study enrolled a large sample of patients seeking care for geni- tourinary complaints, and the results demonstrate significant manage- ment inaccuracies in caring for such patients in an urban ED. Rates of overtreatment are high, particularly in men for whom there was nearly universal presumptive treatment. Rates of missed treatment were also significant, particularly for pregnant females.

Interestingly, proportionally, there was only a small cohort of men

when compared to women. To our knowledge, no study has looked at this phenomenon, but we suspect it is likely due to the more complex differential diagnosis for why women present to the ED (STI concern, pregnancy pain, Vaginal bleeding, bacterial vaginosis, etc.).

For female patients, presumptive treatment occurred less frequently than with males, in part due to the large proportion of pregnant patients in the study. Presumptive treatment among pregnant patients occurred 17% of the time. As has been demonstrated in prior urban ED studies, presumptive treatment of females is often higher when the proportion of pregnant women is less [5,10].

We suspect that lower rates of presumptive treatment in pregnant patients is due to clinician bias towards a pregnancy-related diagnosis

Table 2

infection rate by sex and pregnancy status.

% (n)

Men (n = 50)

Gonorrhea

8% (4)

Chlamydia

20% (10)

Co-infection

3% (1)

All women (n = 1112)

Gonorrhea

4% (48)

Chlamydia

11% (125)

Co-infection

Pregnant women (n = 306)

2% (22)

Gonorrhea

1% (4)

Chlamydia

10% (34)

Co-infection

1% (3)

S.P. Wilson et al. / American Journal of Emergency Medicine 35 (2017) 701703 703

Table 3

Presumptive treatment rates by sex and pregnancy status.

APTIMA assay

Not treated

Presumptively treated

p-Value

Men (n = 50) Gonorrhea

8 (100%)

38 (91%)

0.999

+

0

4 (9%)

Chlamydia

6 (75%)

34 (90%)

0.653

+

2 (25%)

8 (19%)

Women (n = 1110a)

Gonorrhea –

631 (99%)

431 (92%)

b0.001

+

9 (1%)

39 (8%)

Chlamydia –

593 (93%)

392 (83%)

b0.001

+

47 (7%)

78 (17%)

Pregnant (n = 306)

Gonorrhea –

280 (100%)

54 (93%)

b0.001

+

0

4 (7%)

Chlamydia –

257 (92%)

47 (81%)

0.027

+

23 (8%)

11 (19%)

a Two patients missing data.

and expectation for obstetrical outpatient follow-up. As has been found in a prior study, we found high prevalence of disease and high rates of missed treatment among pregnant patients [5]. These results identify a significant opportunity to improve management decision making in this population of patients.

There remains opportunity to improve the accuracy of treatment for patients with possible STIs in urban EDs. Unnecessary treatment is asso- ciated with unnecessary costs and potentially contributes to antibiotic resistance. Particularly in the management of NG, resistance is a grow- ing concern [5,11].

Efforts to reduce overtreatment could include dedicated outpatient resources with adequate access to improve reliable follow-up of test re- sults and treatment as needed. Future studies designed to estimate the risk of STIs with more complex modeling may have a role. Additionally, newer assays for NG and CT could improve the accuracy of ED diagnosis. Many point-of-care assays have been tested but failed to reach adequate sensitivity and reliability [12-18]. More recently, however, a rapid 90- min NAAT assay with improved test characteristics has become avail- able. This assay may provide options for focused treatment in the ED [19].

Limitations

This study was performed at an urban ED, in which presumptive treatment was common. The presentation or practice pattern may not be generalizable to non-urban ED’s. In addition, a significant proportion of pregnant women were included. The applicability in other clinical settings is not known. Enrollment of males was lower than anticipated because males in the study ED were less likely to provide urine samples than females being tested for potential STIs. Finally, there was no provi- sion to follow-up on patients who did not receive treatment during their initial encounter. If they were subsequently able to follow-up and receive appropriate treatment, then missed treatment would not be as concerning.

Conclusions

We observed both a high rate of overtreatment and missed treat- ment for these common sexually transmitted infections. Ample oppor- tunity exists to improve diagnostic accuracy and Treatment decisions.

Prior presentation of data

None.

Conflicts of interest

None.

Financial support

None.

Acknowledgements

None.

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