[Question #2509] Treatment Failure?!

45 months ago

Hi Doc,I had visited a brothel in Mumbai and received unprotected oral sex and protected vaginal sex multiple times in a day (I used 2 condoms each time).  24 hours later, I took 1.5 g Azithromycin and 800 mg Cefixime.  Also, I had taken 2.5g Azithromycin 4 days prior to this as prophylaxis for another incident and estimate that I would have had about 1g of Azithromycin in my system when this incident occured. I know using antibiotics like this is not good and it wont happen again.

 

Therefore, I was very surprised to find urethral discomfort and a clear, watery (slightly sticky) discharge a few days after taking the incident.  This persisted until I went to get a PCR test on urine for gonorrhea and chlamydia 9 days after the incident (i.e. 8 days after antibiotics).  The result was positive for gonorrhea and negative for Chlamydia.  I had to travel for 3 weeks after and could not address the problem, but am finally back home, but the discharge still remains (though scant and clear), and very minor occasional discomfort.  It is now 31 days since the incident and my questions are:

 

1.  Could this be a false positive given the color and consistency of discharge and the medication I took or is it more likely cefixime failure?

2.  What should be my plan of action to test and cure this completely going forward?  Should I retest for gonorrhea now or visit infectious disease specialist for alternate medication?  

3.  What medication is recommended if cefixime failure?

3.  Is there a chance that family members could get infected from sharing toilet seat (from discharge) or towels, etc?

4.  I was worried about HIV due to the gonorrhea so took a Qualitative PCR RNA test 10 days post exposure which was not detectable.  I am going tomorrow for the duo, but do you think I should be worried or would the RNA test results be accurate at 10 days?

 

I thought I was practicing safe sex, but not so sure anymore...

 

Thanks

H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
45 months ago
Welcome to the forum. Thanks for your question.

Although your risk of gonorrhea was very low based on the exposures and treatments you received, it was not zero. The nucleic acid amplification tests (NAAT, including PCR) for gonorrhea are highly accurate and your symptoms were consistent with gonorrhea, so it is apparent you were infected. Most likely it's from the oral sex exposure, although I also wonder about condom failure. Double condoms are not recommended; using two at once increases the risk of condom breakage. OTOH, probably you would have noticed if that had happened. The natural course of gonorrhea is improvement in symptoms over several weeks, and eventually self cure by the immune system. So your improving symptoms does not mean the diagnosis of gonorrhea was wrong. However, the nature of your discharge also seems consistent with nongonococcal urethritis (NGU), and I recommend treatment for both gonorrhea and NGU. It is optional to be retested at this point:  you should be treated even if repeat testing were negative.

Those comments partly address your specific questions, but to be explicit:

1. The gonorrhea test conceivably was false positive, but you shouldn't take that chance. You need treatment for gonorrhea.

2. Testing is optional, and it wouldn't hurt to see a specialist. However, pretty much regardless of that outcom, i.e. even if repeat testing were negative, re-treatment makes sense. Any specialist you might see likely would agree.

3. My choice probably would be ceftriaxone by injection, perhaps in a larger than usual dose (e.g. 500 mg); plus a 1 week course of doxycycline.

4. Neither gonorhrea nor any other STDs are ever transmitted in households through shared toilets, towels, etc. Those are long debunked myths that in past decades were used as excuses in people who denied more obivous risks. Nobody will be at risk of your infection except by sex with you.

5. Ten days is a bit early for RNA testing; those tests typically start to become positive around 10 days, but not reliably until about 15-16 days. The chance you caught HIV is extremely low, despite the apparent gonorrhea. But have a 4th generation (antigen-antibody) test at this time (over 95% conclusive) and perhaps again at 6 weeks (100%).

I hope this information is helpful. Let me know if anything isn't clear.

HHH, MD

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45 months ago
Hi Dr. Handsfield, 

Thanks for your reply.  I do not recall condom breaking, but I never checked. 

I'm a little confused - is it possible that the cefixime and azithromycin actually cured the gonorrhea but when I tested, I did not wait long enough and possibly dead DNA particles were detected?  I have read that these particles can persist for 2 weeks and give a false positive.  Or was there sufficient time between medication and testing that this would not be a possibility?  I never had discharge that was colored or purulent.  Isn't is better to test to see if I still have gonorrhea after the medication before I get retreated, and if I do have it, should I not try to get a culture done for susceptibility to know which antibiotic would work? And if I dont have it, just take the doxy for the NGU?  I'm actually surprised I could have NGU given that I already had azithroymycin in my system and took it again.

Also, is it ok to start taking doxy now and then gonorrhea medicine a few days later or even after doxy treatment is over (or does it have to be initiated on the same day)?  I am in India and no std clinic here like in the US.  Finding a doctor to give me ceftriaxone is difficult - the doctor I went to wanted to give me amoxycillin and another one I went to wanted to give me cefuroxime.  Is there any other medicine besides ceftriaxone (ideally tablet) that I can take instead?

Also, now worried about HIV.  I had read on an earlier post of yours that 10 days for RNA is about 99% accurate (http://www.medhelp.org/posts/HIV---Prevention/RNA-and-oraquick-swab-test-/show/1891685).  Has this assessment changed?  Also, why has the duo test window changed from 4 weeks to 6 weeks all of a sudden?  

I'm trying to recollect my symptoms and it was waking up feeling hot every night for about 2 weeks but not sweating from day 12 (I did not measure my temperature), 2-3 days of bad upper back pain on starting day 18, and raw areas on inside lower lip from day 24 (which is still persisting for a week).  In fact, just today, I woke up with white patches on the lower lip which the doctor said was thrush - these patches are easily scraped off and leave behind a red area and a vertical crack on the inside of lower lip that bleeds from time to time.  Am worried that I actually had ARS.  I have gone for a Duo test today, but now am very worried because of these symptoms, and possibility that the condom broke or was not of good quality and the gonorrhea diagnosis doesnt help either.


Thanks!
H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
45 months ago
Yes, it is possible the test was falsely positive for exactly the reason you state and my reply should have focused more carefully on the sequence of treatment and testing. My apology. DNA detectable by standard testing persists for up to 3 weeks after successful treatment. And there is a phenomenon once called postgonococcal urethritis, or PGU; as the name implies, it occurs when gonorrhea and NGU occurred together, with the NGU becoming apparent after treatment of gonorrhea. The problems with this scenario are that It is unusual to have urethral gonorrhea without symptoms; and the initial azithromycin treatment would be expected to prevent or abort NGU. (PGU was a problem only back in the day when gonorrhea treatment did not also include antibiotics to cover chlamydia and NGU.)

That said, on reflection the possibility you had gonorrhea that never caused symptoms, was treated adequately, but still gave a positive test a few days later is probably more likely than either a false positive test or resistance to the treatment you received. So I'm revising my initial assessment. And therefore, yes:  I do believe it is reasonable to be retested for gonorrhea before embarking on additional treatment for it. However, it also seems likely that you indeed have azithromycin-resistant NGU. When NGU persists after azithromycin, the next step is treatment with doxycycline, so you should go ahead with that.

As for HIV, anytime someone acquires gonorrhea, simultaneous HIV is possible. However, it is very unlikely in this situation. As discussed above, if you acquired gonorrhea, probably it is from the oral sex exposure, not an undetected condom failure. And oral sex is safe sex in regard to HIV:  there has never been a proved case of oral to penis HIV transmission.

If I said plasma RNA testing was 99% sensitive at only 10 days, that was in error even back in the days when I answered questions on MedHelp. In addition, improved data now are available. 10 days is about the earliest that RNA testing is positive; it takes around 15 days to reach 90% confidence and 3+ weeks for 99%. There also are evolving data on 4th generation (duo) test window. That test is over 95% reliable at 4 weeks, but we now know it takes 6 weeks to reach 100% sensitivity. On this forum we began saying 6 instead of 4 weeks about 2-3 months ago.

The mild symptoms you describe are not typical for ARS. And contrary to common beliefs, oral yeast infections (thrush) are not common in ARS; and when it happens, superficial, external manifestations like yours are uncommon. And diagnosis of yeast by simple examination is inaccurate, especially by physicians not highly experienced in this. The odds remain very strongly in your favor, and you can expect a negative result on the test done today.

Let's hold off on further questions until you have the new HIV test result and, ideally, a repeat urethral or urine gonorrhea test as well. In the meantime, you should start taking doxycycline.

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45 months ago
The HIV Duo test result was negative at 32 days.  But the gonorrhea PCR on urine test came back positive again (32 days after I took 800 mg cefixime and 1.5 g azithromycin).

1.  Do you feel that a negative PCR at 10 days and a negative Duo at 32 days is sufficient in combination or do I still need to test at 6 weeks?

2.  What would be your recommendation on complete work up, cure and TOC for gonorrhea now?  I am on my second day of doxycycline currently. 

3.  Little concerned about drug resistant gonorrhea now given the medication and dosage I took.  Would it stand to reason that if it was ineffective on cefixime it would be ineffective on ceftriaxone since they are both cephalosporins?  Plus it seems that macrolides (and now possibly tetracyclines) may also be ineffective?

4.  I was planning to do a VDRL 6 weeks post the incident (which will coincide the day after I finish doxy) - would the doxy affect the results in any way or should I wait to take this test?

5.  Granted that it is better to cure the infection, but if the body cures gonorrhea by itself (drug resistant or not), then why is there so much concern about drug resistant gonorrhea or gonorrhea in general? 


Thanks! 


45 months ago
Also, for any medication or additional testing that you recommend, should I visit an infectious disease specialist, a urologist, or a GP?
H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
45 months ago
1-3. Were you still having urethral discharge when the repeat positive PCR test was done? In addition to starting doxycycline for presumed NGU, were you also given an initial dose of treatment for gonorrhea, such as cefixime or ceftriaxone? For exactly the reason implied in question 3, ceftriaxone is preferred, and should be in a dose of 500 mg instead of the usual 250 mg; ceftriaxone is inherently more active than cefixime by mouth and always preferred for possibly resistant infections. However, I'm now a bit more concerned about the possibility that the lab has a batch of bad tests. That said, you can't take chances, re-treatment is the righ thing. You'll need another test of cure in 3 weeks (even if your symptoms are gone). When that time comes, consider using a different laboratory.

In the meantime, you should speak with your doctor -- before getting ceftriaxone -- about retesting you by culture, in addition to PCR. First, this would help sort out whether PCR is true or false positive. If culture is positive, your doctor and/or the lab should be in touch with public health or other STD expert to discuss the possibility of further testing for antibiotic resistance. To date, cephalosporin resistant gonorrhea has been rare or maybe entirely absent in India (at least to my knowledge). If so, it would be very important for national public health policy to know about cases like yours. As for azithromycin/macrolide resistance, that's not so rare -- but still should be tested if you are culture positive.

4. Syphilis testing is routine whenever someone acquires gonorrhea, but in this case really not necessary. Had you been exposed, the antibiotics (for sure cefixime, ceftriaxone, doxycycline, and perhaps azithromycin) would have aborted the infection and you will never have a positive blood test. So no need for VDRL or other syphilis testing.

5. It takes many weeks or months before self curre, and in the meantime dangerous complications can occur, especially in women but not infrequently in men as well.

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45 months ago
Hi Dr. Handsfield,

Thank you for the information.  

I did not (nor do I currently) have any discharge when I went for the repeat PCR test.  In fact, the only thing I have is occassional urethral discomfort and sometimes an urge to urinate where not much comes out. I also was not given any cefixime/ceftriaxone as was awaiting the results of the PCR when I started the doxy (so currently only on doxy for the 3rd day now).

Should I also need to be checked for DGI or any other complication of gonorrhea?  On recollection, I did have a severe pain in the lower portion of left shoulder blade which was worse on lying down on day 18 for a few days - pericarditis?  But this pain went away.  Or does it take much longer than a month with gonorrhea to get complications?  Will delaying treatment until culture result increase chances for DGI or any other complication?

I also made an enquiry at one of the largest hospitals here and spoke to the head of pathology for the culture.  She informed me that since there was no discharge, a culture would not be possible and she told me to provide a urine sample for culture of gonorrhea.  But I thought urine cannot be cultured for gonorrhea?!  Is she wrong and wouldn't a urethral swab (even without discharge) be the way to go for culture?  Maybe I should find another hospital!  So, have made an appointment tomorrow with an infectious disease specialist at another hospital.  I will also definitely use a different laboratory for the PCR going forward.  I did do a routine urine test and it was absolutely normal and within limits.

Thanks again for your help - much appreciated.  Will let you know how this turns out.  Hopefully I'm not the first case of resistant gonorrhea in India!!!  We do have a problem with fake medication here so hoping that all it is was that I got a bad batch of cefixime.
H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
45 months ago
So I remain suspicious that your most recent gonorrhea test, and perhaps previously, were false positive. At this point there is no way to know for sure.

It isn't possible to have DGI without symptoms, and your symptoms don't suggest it. I've never heard of gonococcal pericarditis. There is little risk of DGI before treatment, even if you have gonorrhea, which I doubt.

It is nonsense that a gonorrhea culture cannot be done without discharge. You either misunderstood the pathologist or she doesn't know much about gonorrhea testing. This is done all the time (or used to be, before urine DNA testing became available) by inserting a small swab 2-3 cm into the urethra. It's uncomfortable, which is one reason urine testing became the norm, but really no big deal. The ID specialist probably will advise you differently.

I hadn't thought of the possibility of counterfeit antibiotics. However, your minor symptoms are strong evidence against gonorrhea. Asymptomatic urethral infection can happen; and I have considerable past experience in research on exactly that topic. However, it is rare and your symptoms are so trivial that I would consider you asymptomatic in regard to gonorrhea.

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45 months ago
Hi Dr. Handsfield,

Just finished my appt with the ID specialist and am more confused than ever!  He agreed with you in that resistant gonorrhea is unlikely in India and both earlier results could be false positive as the DNA may stay for longer.  

He said I had two options:  (1) Take the urethral swab and culture and see what the outcome is, or (2) Begin treatment as if this was Day 0 or assume the strain may be resistant.  He preferred the latter as he said the doxy may adversely affect the culture since I am currently taking it.

But the problem I see is the dosages!  He gave me a prescription for ceftriaxone 1 gram by IV daily for 3 days (IV because its less painful than injection), in addition to Azithromycin 500 mg daily for 14 days, and continue the doxy for a total of 2 weeks!  To me this sounds like overkill and I informed him the same, but he was insistent that this dosage would cover any resistant strain as well. 

I was thinking of just going for only the first day of ceftriaxone 1 g and leave it at that since I am already taking doxy (and will finish in 3 more days).  Then, after 3 weeks, take a urine PCR at a  different lab.  Would you agree, or should I still do the culture and maybe find another doctor (which seems difficult here)?!

Really appreciate your continued help and advice.

Thanks!
H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
45 months ago
I see nothing confusing in the advice you have had from the ID specialist, and I agree with it. I was forgetting that you are on doxycycline (your situation is a bit complex and I didn't keep track of all details). It is correct that this make culture for gonorrhea impractical. Given the overall situation, giving the very high dose treatment the specialist recommended makes sense. I agree it may be overkill to take both azithro and doxy for the duration recommended, but it's the conservative, safe thing to do in this situation. I agree these doses would adequately treat even the most antibiotic resistant strains of gonorrhea reported to date. I recommend you follow the specialist's advice and see no need for yet another medical opinion.

That will have to conclude this thread; we're already past the normal two follow-up comments and replies included with each question. I recommend you direct any further questions to your ID physician.

I hope the discussion has been helpful. Best wishes and stay safe.
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