Alexander McMillan1, 2
(1)
Department of Genitourinary Medicine, NHS Lothian, Edinburgh Royal Infirmary, Edinburgh, Uk
(2)
University of Edinburgh, Edinburgh, Uk
Alexander McMillanFormerly, Consultant Physician, part-time Senior Lecturer
Email: a.amcmm@btinternet.com
Abstract
Sarah, a 17-year-old woman, who is 14 weeks' pregnant attends a Sexual Health clinic as a sexual contact of a man with proven urethral gonorrhoea and chlamydial infection. She has noticed some increased vaginal discharge, but she is otherwise symptomless. For the past 6 months she has been in a relationship with the man who is her first and only sexual partner. He had had unprotected oral and vaginal sex with a woman from London about 3 weeks previously, and he had vaginal intercourse with Sarah 1 week later. At that time he was symptomless. She has documented hypersensitivity to penicillin, having had an anaphylactic reaction after receiving penicillin for the treatment of a dog bite several years previously.
Sarah, a 17-year-old woman, who is 14 weeks' pregnant attends a Sexual Health clinic as a sexual contact of a man with proven urethral gonorrhoea and chlamydial infection. She has noticed some increased vaginal discharge, but she is otherwise symptomless. For the past 6 months she has been in a relationship with the man who is her first and only sexual partner. He had had unprotected oral and vaginal sex with a woman from London about 3 weeks previously, and he had vaginal intercourse with Sarah 1 week later. At that time he was symptomless. She has documented hypersensitivity to penicillin, having had an anaphylactic reaction after receiving penicillin for the treatment of a dog bite several years previously.
Increased vaginal discharge is common during pregnancy and this symptom does not necessarily indicate infection. There is a high probability, however, that she is infected.
Specimens for culture for Neisseria gonorrhoeae are obtained from the urethra, endocervical canal, anorectum, and pharynx, and endocervical material is taken for the detection of Chlamydia trachomatis (see Case 2). Gram-smear microscopy of urethral and endocervical material shows many polymorphonuclear leucocytes but Gram-negative diplococci are not identified. Microscopy of a saline-mount preparation of vaginal material does not showTrichomonas vaginalis. Tests for treponemal and HIV infections are taken.
Sarah is offered and accepts empirical treatment.
The reasons for this decision to offer empirical treatment for gonococcal and chlamydial infections are outlined in Cases 6 and 8.
Table 28.1shows the results of the antimicrobial susceptibility testing of the Neisseria gonorrhoeae isolated from her partner's urethra.
Table 28.1.
Antimicrobial susceptibility results.
Antimicrobial agent |
Interpretation of susceptibility result |
Penicillin |
Resistant |
Tetracycline |
Sensitive |
Ciprofloxacin |
Sensitive |
Azithromycin |
Sensitive |
Spectinomycin |
Sensitive |
Ceftriaxone |
Sensitive |
Cefixime |
Sensitive |
28.1 What Would Be Your Choice of Antimicrobial Agent(s) in This Case?
Consider first the treatment of gonorrhoea in a pregnant woman. Tetracyclines and the quinolones are contraindicated in pregnancy.
Although the cephalosporins ceftriaxone and cefixime are highly active against N. gonorrhoeae, there is concern about the administration of these drugs to individuals with a documented history of penicillin hypersensitivity. About 8% of persons with penicillin allergy show hypersensitivity reactions when given a cephalosporin. Skin testing for cephalosporin hypersensitivity may identify those who are unlikely to develop a serious reaction, but such tests have not been fully standardized and are not generally available.
As azithromycin is useful in the treatment of genital chlamydial infection that is commonly found in association with gonorrhoea, it is tempting to consider this agent. There are, however, concerns about its use. Although a 2 g single oral dose of azithromycin has been shown to be effective in the treatment of gonorrhoea, this dose1 results in a high incidence of gastrointestinal side effects. The emergence of resistant strains of N. gonorrhoeae is of concern, and, although the infecting strain appears sensitive to azithromycin in vitro, this may not accurately reflect efficacy in the clinical situation.
Spectinomycin, given as a single intramuscular injection of 2 g, is the treatment of choice in this case. It is highly effective against N. gonorrhoeae has few side effects and is safe to use in pregnancy.
Treatment of probable concurrent chlamydial infection needs to be considered.
Although azithromycin appears to be safe and many clinicians prescribe it for the treatment of chlamydial infection, it is not licensed for use in pregnancy, and current UK guidelines recommend its use only when there are no satisfactory alternatives. In a meta-analysis of randomized controlled trials, single-dose azithromycin was shown to be as effective as a course of erythromycin in the treatment of pregnant women but was associated with fewer adverse events. Table 28.2 indicates the antimicrobial agents that are currently recommended for use in pregnant women with chlamydial genital tract infection.
Table 28.2.
Antimicrobial drugs recommended for use in pregnant women with chlamydial genital tract infection.
Erythromycin 500 mg four times daily by mouth for 7 days |
OR |
Erythromycin 500 mg twice daily by mouth for 14 days |
OR |
Amoxicillin 500 mg three times per day for 7 days |
Sarah is treated with spectinomycin and erythromycin, given in an oral dose of 500 mg twice daily. She is invited to attend the clinic 1 week later.
At this time the results of the microbiological tests are available:
· Neisseria gonorrhoeae was isolated from the urethra, endocervical canal, and anorectum but not from the pharynx. The antimicrobial susceptibility pattern of the isolate was identical to that of her partner’s.
· Chlamydia trachomatis DNA was detected in the endocervical sample.
· Serological tests for syphilis and HIV were negative.
She has not had sexual contact since initiation of treatment.
The reason for review at this time is to ensure that the treatment regimen is well tolerated and that there has been no risk of re-infection. As she has been treated with a drug to which the infecting strain is sensitive, this has been given under supervision, and there is no apparent risk of re-infection, a test of cure for gonorrhoea is not indicated.2
As efficacy of treatment of genital chlamydial infection in pregnant women with any of the drugs listed in Table 28.2 (and of azithromycin) is thought to be <95%, a test of cure should be undertaken (at least 5 weeks after completion of therapy if a nucleic acid amplification assay is used).
28.2 What Are the Risks of Untreated Gonococcal and Chlamydial Infections in Pregnant Women?
(a)
In pregnant women, untreated gonorrhoea is associated with an increased risk of
· Chorioamnionitis;
· Intrauterine growth retardation;
· Premature rupture of the membranes ;
· Pre-maturity;
· Low birth weight;
· Fetal death;
· Post-partum PID;
· Post-termination endometritis;
· Disseminated gonococcal infection in the mother (see Case 24). Pregnancy is a predisposing factor to dissemination, particularly during the third trimester.
Neisseria gonorrhoeae can also be transmitted to the neonate during vaginal delivery and result in ophthalmia neonatorum (Fig. 28.1). The risk of transmission from an infected mother is estimated to be between 30 and 50%. Most infants develop conjunctivitis within 24–48 h of birth. The eyelids swell and pus collects in the conjunctival sac. Keratitis with corneal scarring may result if the condition is not treated.
Figure 28.1.
Gonococcal ophthalmia neonatorum.
(b)
Untreated chlamydial infection may be associated with the following:
· Premature rupture of the membranes and premature delivery, although the evidence is inconclusive.
· Neonatal transmission. About 75% of infants delivered vaginally to infected mothers, and just over 20% born by Caesarean section to infected women with intact membranes become infected. The latter finding suggests that infection in utero is possible. Conjunctivitis, developing 3–13 days after birth, and varying in severity from mild to severe, is the most obvious clinical presentation of chlamydial neonatal infection. In the absence of specific treatment, the course is usually benign. The sight is not compromised, although micropannus and conjunctival scarring may occur. Infection is not confined to the conjunctiva, and the respiratory tract, the middle ear, the gut, and the vagina can be also become infected. Spread of the organism from the nasopharynx to the lower respiratory tract can result in pneumonitis, with an estimated incidence of 11–20% of babies born to infected mothers. The onset of the pneumonitis occurs later than that of conjunctivitis, usually between 3 and 11 weeks. The infection is generally mild and self-limiting, but treatment in the form of erythromycin is often advocated.
Footnotes
1
A single oral dose of 1 g of azithromycin is used for the treatment of genital chlamydial infection. This dose, however, has not been shown to be very effective in the treatment of gonorrhoea.
2
If a test of cure is undertaken, this should be performed at least 72 h after completion of antimicrobial therapy. As cure of infection of the pharynx is less certain than infection of the genital tract or anorectum, at least one test of cure should be performed if gonorrhoea is identified at this anatomical site.