STD Prevention Conference-Telebriefing Transcript

Telephone Press Briefing: New Developments in Antibiotic-Resistant Gonorrhea

MERMIN: Good afternoon everybody. I am Dr. Jonathan Mermin and I’m Director of the National Center for HIV/Viral Hepatitis/STD and T.B. Prevention at CDC. I’m accompanied here today with Dr. Stephanie Taylor, Dr. Gail Bolan and Dr. Alan Katz. And I’ll be introducing them all separately in a moment.

I’m speaking to you from Atlanta, where more than 1,200 people have gathered for the 2016 National STD Prevention Conference. It’s a scientific meeting that we convene every other year. And today’s briefing is focused on the increasing threat posed by antibiotic resistance. Specifically the threat of drug-resistant gonorrhea. We’re seeing new troubling signs that our current gonorrhea treatment may be losing its effectiveness, but we have not seen the treatment failure in the U.S. when the recommended treatment has been used. We have identified the first cluster of gonorrhea cases in the U.S. to show decreased susceptibility to both of the currently recommended drugs.

While we’re reporting signs of worsening resistance, there are steps we can take to slow the course, including following treatment guidelines and the development of new treatment options. Several drugs for gonorrhea treatment are in late-stage clinical trials and today we will discuss findings from one clinical trial being presented at this week’s conference. We’ll also discuss CDC’s ongoing efforts to monitor for resistance and our ability to respond rapidly when resistance is detected.

So before diving into the findings I wanted to paint a picture of the severe impact of gonorrhea in the U.S. Gonorrhea is a serious and a costly disease. Gonorrhea is one of the most common sexually transmitted diseases. There are about 800,000 infections in the United States each year, only half of which are diagnosed and reported to CDC. If not diagnosed and treated, gonorrhea can cause chronic pelvic pain, infertility and life threatening ectopic pregnancy. It can also increase a person’s risk for acquiring or transmitting HIV.

Gonorrhea also imposes a substantial burden on our public health and healthcare systems. We estimate the lifetime medical cost of treating gonorrhea for people born in just a single year at up to about $92 million.

So there are new signs that we may be running out of options for treating gonorrhea. Over the years, gonorrhea developed resistance to nearly every class of antibiotics used to treat it, and today dual antibiotic therapy, that combines a single shot of ceftriaxone and an oral dose of azithromycin is the only recommended option that is left.

The first thing we’ll highlight details findings from a joint investigation by the Hawaii State Department of Public Health and CDC into a concerning cluster of gonorrhea infections in Hawaii. It’s the first cluster of cases to show decreased susceptibility to both drugs, and the findings are even more concerning than data CDC published earlier this year that showed evidence of emerging azithromycin resistance across the nation. But those cases were all susceptible to ceftriaxone.

These are the latest signs that the effectiveness of today’s treatment may soon be in jeopardy. CDC routinely tests isolates from gonorrhea cultures around the country for signs of decreased susceptibility. Meaning that a higher concentration of antibiotics is required to kill the gonorrhea bacteria in the lab. It’s important to note that all the patients in Hawaii who were identified as part of this cluster were successfully treated. But for (ph)the current recommended drug combination the findings are also a red flag. If resistance continues to increase and spread our current treatment regimen will eventually fail.

So that’s why we welcome encouraging findings from a second study we’re highlighting which shows progress on an experimental new treatment for gonorrhea. We’ll hear from Dr. Stephanie Taylor from Louisiana State University, the study’s lead investigator. She and her colleagues found in a phase two clinical trial that a new drug, known as ETX0914 was safe and effective at curing gonorrhea.

These findings are promising, but we urgently need more treatment options in the pipeline. It takes years to bring new drugs to market. So it’s critical for researchers and pharmaceutical companies to jump start additional research on new gonorrhea drugs and drug combinations.

Now I’ll turn it over to Dr. Alan Katz, Professor of Public Health at the University of Hawaii and member of Hawaii’s State Board of Health, to tell us more about the joint investigation in Hawaii. Dr. Katz?

KATZ: Thank you very much Dr. Mermin, and thank you for the opportunity to present a summary of our findings. As Dr. Mermin noted this is a collaborative effort between Hawaii’s State Health Department, the CDC and the University of Washington. I’m scheduled to give a more complete overview as well as a presentation on Thursday morning.

The emergent spread of antibiotic-resistant Neisseria gonorrhea, the bacteria that causes gonorrhea, has been identified as a major health threat by both the World Health Organization and the CDC, and as Dr. Mermin noted, resistance has successively developed to penicillin, tetracyclines and fluoroquinolones. Since 2010 the CDC has recommended the dual therapy for gonorrhea treatment using a cephalosporin plus either azithromycin, which is preferred, or doxycycline.

Decreased susceptibility to cefixime, which is an oral cephalosporin in the United States, and treatment failures in other countries led the CDC to recommend against its use as a first line gonorrhea treatment in 2012. The current dual therapy recommendation is to use an injectable cephalosporin, cetrox ceftriaxone at a dose of 250 milligrams intermuscularly, plus one gram of oral azithromycin. The State of Hawaii has been a sentinel site for monitoring Neisseria gonorrhea resistance, and the Hawaii State Department of Health has been one of the original CDC’s gonococcal isolates surveillance project, GISP or GISP surveillance sites, and has participated in GISP since its inception in 1986.

As part of GISP we submit gonococcal isolates from the first 25 men seen each month with gonorrhea to a regional GISP laboratory. Our regional lab is the University of Washington in Seattle, which then transmits results to the CDC Atlanta. In addition the Hawaii State Department of Health also independently conducts Neisseria gonorrhea isolate surveillance and performs their own antibiotic susceptibility and testing of isolates using Etest.

From 2010 through 2014, isolates were obtained that tested from approximately 25 percent of the gonorrhea cases diagnosed in the State of Hawaii. The proportion of diagnosed gonorrhea cases from which isolates were obtained and for which antibiotic susceptibility testing was done is higher than any other state. It’s substantially higher than the approximately 4 percent of male gonorrhea patients sampled nationally in GISP.

Hawaii is located between Asia, where we believe many resistant strains originate, and the mainland U.S. It was one of the first states to identify Neisseria gonorrhea isolates with high level resistance to penicillin and fluoroquinolones, and decreased susceptibility to cefixime. It was also the first state in the United States to identify Neisseria gonorrhea isolate with high level resistance to azithromycin.

From April 21st to May 10th, 2016, eight gonococcal isolates from seven patients demonstrated very high azithromycin Etests minimum inhibitory concentrations, or MICs. MICs measure the concentration of an antibiotic necessary to inhibit bacterial replication in the lab setting. The higher the MIC measured in micrograms per milliliter, the greater the amount of antibiotic necessary to inhibit bacterial replication.

The MIC levels suggested high level resistance to azithromycin. Most of the isolates also demonstrated elevated MICs to ceftriaxone. The Hawaii state laboratories performed additional genetic testing of the isolates. One test, pulse field gel electrophoresis, also termed DNA fingerprinting, showed the isolates to be genetically related to each other. Isolates were then sent to the University of Washington Regional GISP lab and CDC Atlanta to do the gold standard agar dilution antibiotic susceptibility testing. High levels of azithromycin resistance was confirmed in all eight isolates using the agar dilution antibiotic susceptibility method, with MICs greater than 16 micrograms per ml. All isolates were resistant to penicillin, tetracycline and ciprofloxacin and had elevated MICs to gentamicin.

As part of the CDC’s advanced molecular detection initiative, Hawaii state laboratories also conducted whole genome sequencing of the isolates, and submitted the sequences to the CDC for analysis. That analysis demonstrated a tight cluster, suggested clonal expansion of a single clade, in other words the genetic analysis by two methods — the whole genome sequencing and the full scale (ph) gel electrophoresis — indicated the isolates were closely related and perhaps had a common origin.

Clinically all our patients — six males and one female — were symptomatic with dysuria, which is pain on urination, and/or discharge from the penis or vagina. All were interviewed and all were successfully treated with the recommended dual therapy of 250 milligrams ceftriaxone intermuscularly as well as one gram azithromycin. None of our patients reported any recent travel or antibiotic use, and no male patients reported having male sex partners.

The seven case patients reported eight sexual partners, of which four were located and tested. All tested negative. The sole female case patient named two partners, one of whom had been previously diagnosed with gonorrhea, with a urine nucleic acid amplification test, that disallowed culture of antibiotic susceptibility testing. He had been diagnosed and treated. We interviewed him, he tested negative, and he’s the only documented gonorrhea-infected partner to one of our cluster of patients.

The national GISP data from 2014 did show increased prevalence of reduced susceptibility to azithromycin, however the isolates with reduced azithromycin susceptibility were highly sensitive to ceftriaxone. The Hawaii cluster is concerning, as all eight isolates demonstrated high levels of azithromycin resistance, resistance to penicillin, tetracycline and ciprofloxacin, and five of the eight demonstrated reduced susceptibility to ceftriaxone by agar dilution testing, and the isolates were genetically related.

Development of higher Ceftriaxone MICs, and widespread transmission of such strains could severely complicate gonorrhea treatment. While all of our patients were successfully treated, and no documented treatment failures have occurred with the currently recommended dual therapy — the Ceftriaxone plus Azithromycin — in the United States the first documented case of a gonorrhea treatment failure after recommended dual therapy was recently reported from the United Kingdom.

The isolate had a Ceftriaxone MIC of .025 mcg/mL. And the Azithromycin MIC was 1 mcg/mL. In comparison, the Hawaii isolates demonstrated much greater resistance to Azithromycin. And in five isolates, the Ceftriaxone MICs were only a single dilution lower than the Ceftriaxone MIC from the UK.

Our findings underscore the value of CDC’s recommendations for laboratories to maintain or reestablish culture-based methods to detect antimicrobial resistance in Neisseria gonorrhea, particularly for patients with possible treatment failure. It’s important for physicians to be on high alert so that treatment failures can be identified and reported promptly to their local Department of Health, and the CDC.

This concludes my remarks and I’ll now turn it back over to Dr. Mermin.

MERMIN: Thank you, Dr. Katz. It would seem that in the battle between humans and pathogens, gonorrhea is a formidable opponent. And to discuss that more, I’d like to turn over the podium to Dr. Stephanie Taylor.

TAYLOR: Good afternoon everyone. And thanks to Dr. Bolan and to Dr. Mermin, the CDC for this opportunity to present briefly our findings from a drug trial that we recently completed.

We performed a Phase II randomized control trial, single dose, oral, EXT RETX 0914, for the treatment of uncomplicated Urogenital gonorrhea. Meaning urethral and cervical. ETX 0914 is a novel antibiotic that is under development by Entasis Therapeutics. The thing that’s different about this antibiotic, and that we’re really pleased with, is that it has a different mechanism of action by which it kills the organism.

And so we’re please that this — and welcome a possible addition to our armamentarium to fight gonorrhea. So men and women were eligible for our study if they had been diagnosed with gonorrhea in the past two weeks prior to enrollment, if they had been in contact to someone who had been diagnosed with gonorrhea in the two weeks prior to enrollment, or if they had signs and symptoms of gonorrhea, themselves.

So from November, 2014 through December, 2015, we enrolled 179 patients or participants. 167 were men, 12 were women, 18-53 years old. They were randomized to receive either two or three grams of the new study drug, ETX 0914. Or 500 mg of Ceftriaxone by intramuscular injection. The primary end point was eradication of the organism that was measured by negative cultures for gonorrhea at the test of cure visit.

In the per protocol population, 98 percent, or 48 of 49 participants converted their cultures from positive to negative by the test of cure. And 100 percent of the 47 in the 3g arm, and the 21 in the Ceftriaxone arm were able to — had negative cultures at the test of cure visit. Only 21 participants who received ETX 0914 reported any adverse events. Most of these were gastrointestinal and they were determined to be related to ETX 0914.

So we found that this study drug, ETX 0914, was safe and effective in treating uncomplicated Urogenital gonorrhea. So we are very encouraged by these results, we look forward to this study drug moving on to further clinical trials. And once again, we are pleased that we now have an antibiotic, with a different mechanism of action to kill bacteria, at our disposal.

I would like to thank the NIAID, who had — we had contract support for this trial. Entasis and the other participating sites (ph). University of Washington in Seattle, Indiana University, University of Alabama at Birmingham, and the University of North Carolina at Chapel Hill, Indiana University. Thank you very much for your attention. And I now turn it back over to Dr. Mermin.

MERMIN: Thank you, Professor Taylor. It’s now my pleasure to ask Dr. Gail Bolan, Director of CDC’s Division of STD prevention, to come up and talk about the national response to the threat of drug-resistant gonorrhea.

BOLAN: Thank you, Dr. Mermin. Today’s news from Hawaii reinforces the urgent need to strengthen efforts to fight gonorrhea, prolong the effectiveness of today’s treatments, and prevent infections before they occur, not just in Hawaii, but throughout the United States.

This means that maintaining our focus on routine gonorrhea testing and treatment services, enhancing systems that monitor for emerging drug resistance, and building rapid detection and response capacity to address potential outbreaks.

As Dr. Katz indicated, the Hawaii outbreak was successfully contained. And everyone found who was linked to the cluster was treated. Thanks to robust monitoring and rapid response efforts.

The Hawaii State Department of Health routinely obtains and cultures gonorrhea. Which enables it to quickly identify the resistant strain and treat the seven affected individuals, protecting their health and preventing further infections.

But not all states conduct their own testing of gonorrhea isolates. That’s why CDC leads the gonococcal isolate surveillance project known as GISP — a partnership with regional labs and STD clinics across the nation. This project enables us to identify resistant strains and monitor national trends.

CDC also funds STD prevention services in every state, with support for surveillance, disease investigation, and health promotion, along with guidelines, training, and tactical (ph) support. This funding includes all 50 states, to decrease the burden of STDs, and programs like the Community Approaches to Reducing STDs, known as CARS. Which leverages community resources, and partners to reduce STD disparities (ph).

And because drug-resistant gonorrhea is one of the key national threats identified in the Federal Government’s National Action Plan for combating antibiotic-resistant bacteria, CDC is implementing targeted efforts against the threat of untreatable gonorrhea, specifically.

These include introducing new laboratory tests to more rapidly detect gonorrhea strains and — with decreased susceptibility. And helping state and local Health Departments build rapid epidemiologic response capacity for outbreaks.

Finally, I’d like to say a few words about the critical role of health care providers in gonorrhea prevention. We need healthcare providers to take action in several ways. First, increased gonorrhea screening is absolutely essential. As Dr. Mermin said, gonorrhea is the — one of the most common sexually transmitted infections, but most people do not realize they have it. The only way they find out is through testing.

Second, it’s critical for healthcare providers to follow CDC’s STD treatment recommendations. That means promptly treating all gonorrhea cases with a combination of both Ceftriaxone and Azithromycin. Using both drugs ensures that you’ve fully cured the infection, and prevent transmission to others.

Third, clinicians should be on a high alert for treatment failures. Any suspected case of treatment failure should be retested, ideally cultured and properly reported to the local health officials and then to CDC. So I thank you. And I’ll now hand it back to Dr. Mermin.

MERMIN: Well, thank you Dr. Bolan. So, just before we open it up for questions, I wanted to highlight four roles that we can all play in, in responding to the growing threat of gonorrhea.

The first is Dr. Bolan noted, healthcare providers should — should make sure that they’re fully implementing CDC’s STD treatment guidelines. That means screening all appropriate patients for gonorrhea and other STDs, treating gonorrhea cases promptly with ceftriaxone and azithromycin, and staying on high alert for treatment failure. State and local health departments should continue to strengthen systems for detecting and responding to drug resistant gonorrhea

And CDC will continue to do all that we can do to support them. Pharmaceutical companies, researchers, and other partners can work together to intensify and accelerate research on better diagnostic tests that includes susceptibility results and new gonorrhea treatments. Even if the new treatment we heard about today is successful, it is clear that we’ll need to develop even more options quickly.

And lastly, anyone concerned about the risk for gonorrhea should talk to their healthcare provider. Despite the growing threat of drug resistance, gonorrhea continues to be preventable, treatable, and curable. And a sustained focus on regular testing, dual antibiotic treatments, and careful resistance monitoring are essential to fend off the threat of untreatable gonorrhea.

So — so now, I — I would like to open up to any questions for reporters that are in the room. And then we’ll open up the telephone. Yes?

Sorry, we have Michael Smith from MedPage Today.

QUESTION: Thank you, Dr. Mermin. It’s Michael Smith from MedPage Today. I have a bunch of questions (inaudible).

I don’t know with the (ph) lineup, but I’ll just go ahead and (inaudible). Dr. Katz, please — so just a — a technical question. You referred several times to eight isolates, and then you had six men, and one women (ph) — and my arithmetic is rusty…

KATZ: There was one patient that had an isolate from his urethra and from a urine specimen. It’s very unusual to get a gonorrhea organism to grow in urine.

And we had two private practice doctors that ordered urine culture in (ph) sensitivities, as well as the urethral swab cultures. And they were — you know incidentally, they were able to grow gonorrhea. They were looking for urinary tract infections.

But they were able to isolate gonorrhea from the urine. So one of the cases just had a urine specimen, the other had both the urethral and the urine specimen. So there was eight ‘cause one patient had two isolates…

QUESTION: That’s unusual — unusual…

KATZ: And a usual — yes in fact we’re — our lab is writing that up as a case report there. You could –isolation of gonorrhea from a urine specimen, because it is unusual.

QUESTION: Eventually you treated people with this drug combination and cured them. Did you have to up the doses? What — what did you actually have to…

(CROSSTALK)

KATZ: We used the regular dose. And we only retreated one person. So, everyone else was treated according to the CDC’s guidelines — 250 milligrams of injectable ceftriaxone, and the one gram oral azithromycin.

And even though the organism was highly resistant to azithromycin, it was still susceptible to the ceftriaxone. So, it’s basically the ceftriaxone that took care of it.

And one — one person had duxycycline and azithromycin. And that person was treated when we got the results of the culture — antibiotic susceptibility test. And we treated him appropriately with the ceftriaxone/azithromycin dual therapy.

QUESTION: How — how were these cases discovered? Isn’t — through — it wasn’t through treatment failure?

KATZ: No.

QUESTION: No (ph).

KATZ: This was discovered because our lab is aggressively doing culture isolation and antibiotic susceptibility testing. We are the leaders in the nation — I mean CDCs are the leaders in the nation. But we’re the — we’re the state individual leaders in the nation in Hawaii.

QUESTION: And totally resistant (inaudible) — the function of the fact that you have this…

(CROSSTALK)

QUESTION: …aggressive testing regimen…

(CROSSTALK)

KATZ: Yes, we’re — we’re — we’re on top of things. In fact, you know people come to Hawaii to vacation, the CDC comes to work. They come to go to our lab and look for our isolates.

QUESTION: OK. I think that’s — there’s probably others. But they’ll come up with the rest of it (ph).

And just one question for Dr. Taylor, if I may. Dr. Taylor, you said this is — this drug has a different mechanism of action. Can you elaborate on that compared to other…

(CROSSTALK)

TAYLOR: Yes, it — it has a different mechanism of inhibiting DNA synthesis of the organism. It does impact the DNA drawings (ph) of the organism, and — and performs — or makes the (ph) shortchange (ph) that interrupt synthesis of DNA and kills the organism.

QUESTION: Thank you.

MERMIN: Good. Yes?

QUESTION: It’s Matt Hennie with Project Q Atlanta. Dr. Mermin, in July I think you and Dr. Bolan talked a little bit about the gonorrhea resistance and how it was impacting (inaudible) with men. Is that still the case?

And can you talk a little bit about that and why that might be?

MERMIN: (Inaudible)

BOLAN: Yeah, I mean I think in general, the trends that we’ve seen and — and been able to detect through our GIS (ph) you know monitoring project is that we usually see emerging decrease susceptibility or resistance coming from the West, starting with Hawaii. And then we also see a higher proportion of isolates with decreased susceptibility among men who have sex with men.

And this has been a pattern that we’ve seen for the penicillin resistance, the fluoroquinolones resistance, the decrease susceptibility to cefixime. We’re still there — you know and we’re seeing similar patterns with our azithromycin report that came out a — a few months ago. Still, the numbers for decreased susceptibility to ceftriaxone is very low in this country.

So, we’re monitoring it very closely. And I — and I don’t think we’ve got enough numbers yet to say what the trends are in terms of geographic and sexual orientation.

MERMIN: Any further questions for the room? So, operator, could you please explain to the people on the telephone how they can queue up?

OPERATOR: Ladies and gentlemen, if you wish to ask a question, please press “star” then “one”. You will hear a tone indicating you’ve been placed into queue. You may remove yourself from the queue at any time by pressing the “pound” key.

Once again, “star” “one” at this time. We have a question from Amy Fox (ph) with NBC (ph) News. Please go ahead.

QUESTION: Hey, thanks very much. Can you talk about how you knew these cases were antibiotic resistant? I take it — it was not at all evident clinically.

You were able to cure all of them with one dose — or one person had a second dose. Is that right?

KATZ: Only one person got a second treatment. And it was done as soon as we got the antibiotic susceptibility test back.

And — and that patient actually was reported definition (ph) of the symptoms. He reported that his symptoms had resolved. So he was — again, the thing to stress is these isolates were decreased susceptibility in the ceftriaxone, but they weren’t resistant to ceftriaxone.

They were at the level that we consider sort of alert level. And — and the one done (ph) publically reported treatment failure with the dual therapy had a much — well, not — it — it had twice the MIC as our isolate for the sub-trioxin (ph) was 0.25 micrograms per ml.

So, we were aware of the cluster by virtue of our normal surveillance activities for gonococcal isolates. We try to get as many cases as we can diagnosed with cultures and our STD clinic is very active in doing that. So, like I said, about a quarter of our gonorrhea diagnoses are done by cultures and all of those have antibiotic susceptibility testing. So, no treatment failures.

QUESTION: So this is something that you’re not going to notice unless you’re looking for it?

KATZ: That’s a big problem, yes. Unless you’re doing cultures, you may not find that so one of the things that the CDC has emphasized is, again, if you fear a treatment failure, it’s imperative to get a culture.

BOLAN: And Dr. Katz, this is Dr. Bolan and I just wanted to clarify. So, the patient that you had to retreat, they were not treated with the CDC recommended regimen initially?

KATZ: That’s correct. Actually, you’re right, the one person — but he gave a history of decreased symptoms. We’ve actively — because we get the results back relatively quickly, the cultures grow in a couple of days. The antibiotic susceptibility is done with e-test (ph) rather than the honor (ph) dilution so it’s a quite rapid process. And then we went out and we treated him and then we did a test of cure and he was cured.

BOLAN: I think you bring up an important point that we see commonly, clinically, is that when providers do not treat according to our recommendations and use a different regimen they think is going to work, patients with symptoms actually feel better. Their symptoms are reduced but they still have the organism and so, unfortunately for a lot of patients, if you think that your symptoms have gone away, you don’t feel the need to come back in and you feel like you’ve been cured of your infection.

So, it’s another area that we need to educate both providers and patients that if you’re not treated correctly, you can’t rely on your symptoms telling you whether or not your body’s been cured. You really need to come back in and get checked if the health department’s calling you and saying you need to come back in and be treated again.

QUESTION: So, in other words, what you’re saying is these drug resistant infections could be out there incubating in people who don’t even know they have them?

BOLAN: That’s one of our concerns and that’s why we’re really encouraging both providers and health departments to start scaling up their ability to detect these strains.

QUESTION: And can I ask, you said you had a hard time tracking down your sexual partners and nobody had a sexual partner with the same organism. What does that indicate to you?

KATZ: So, on the sexual partners that we brought in, we had eight partners identified, we got half and that’s pretty good and that took field trials. Our field work, people on the ground, they actually went out and got people to come into the clinic. One girlfriend was in Japan and she reported that she had been treated in Japan and tested negative but we don’t have access to her records. And one index case, one case patient just, you know, named a partner, said that he had one partner but he refused to talk to us about it.

QUESTION: So where’d these people get infected?

KATZ: Where did they get infected? From…

QUESTION: …With the resistant strain?

KATZ: They could have gotten infected and not had their isolate identified because it’s the — like we’ve said, this isolate has reduced susceptibility to sub-trioxone (ph). It’s not resistant to sub-trioxone (ph) so if somebody was treated with the regular therapy, they’d be cleared, that would take care of it. So, if their partners had gone — we were aware of one partner with gonorrhea but we weren’t able to get ahold of an isolate from him because his doctor did a nucleic acid amplification test.

Most of the gonorrhea testing that’s being done today is being done using molecular test methods, it’s not being done with cultures. Hawaii’s sort of unique in that regard. That’s why a lot of work and a lot of CDC folks come out to Hawaii and we have really good surveillance because we’re doing such aggressive culturing. And again, reestablishing the culturability is one of the goals, I think, that the CDC has stated.

QUESTION: And I’m sorry, may I just ask one more? Because I wanted to ask about the new antibiotics. I’m not clear on whether it’s a completely new class, if it’s a fluoroquinolone; exactly how unique it is.

TAYLOR: All right, I’ll answer this question and then I wanted to go back to a clinical question. So, can you repeat your question again?

QUESTION: Yes. The new antibiotic, is it a completely new class? Does it count as a fluoroquinolone? How does it count?

TAYLOR: It doesn’t count as a fluoroquinolone, although it does interact with DNA gyrase in a different way or in a different location than fluoroquinolone. So, it is completely different from fluoroquinolone.

QUESTION: So, if this goes through, it would be the first in a new class of antibiotics since 1984; is that correct?

TAYLOR: Since 1984? I would have to double check on the year, but yes, it would be a brand new class of antibiotics. There are none marketed, none on the market right now with this mechanism of action.

QUESTION: Thank you.

TAYLOR: Now, my clinical comment goes back to partners and goes back to providers, and it’s important that, when partners present, they are commonly asymptomatic. But, they do need to be tested and treated that day that they present. Some patients want to wait, the partners want to wait for test results. It is important that the test and treatment happen on the same day, even though they’re having no symptoms.

BOLAN: And the other clinical comment, this is Dr. Bolan again, I’d like to add that relates to this discussion, is because of our concern and because we know waiting for a symptomatic person to come in with a treatment failure is going to really just be the tip of the iceberg, and we’re worried these strains will have spread too far for us to have a good handle on untreatable gonorrhea, is we are recommending in our treatment guidelines, if you don’t use our recommended regimen, which is only Ceftriaxone and Azithromycin, you need, especially if you have oral gonorrhea, you need to bring the patient back in for a tested cure and patients need to be educated about this, and providers do, and usually people get back within seven days. So, that’s another way we’re hopeful that if there is some concerning strains, we’ll be able to pick them up that way.

(UNKNOWN): Any other questions on the phone?

OPERATOR: Our next one is from Liz Heiliman (ph) with the Bay area. Please go ahead.

QUESTION: Yes. Another question for Dr. Taylor, I’d like to know what the status of this drug is now, whether it’s looking to move into phase three trials and where those might be enrolling and what the timeframe for that is.

TAYLOR: No, all of those questions are a bit premature right now, and so I would refer you to the company for some specifics about that. But this is just the completion of the phase two trial, and we are looking forward to it advancing to phase three, but that is not determined at this point.

(UNKNOWN): Other questions, operator?

OPERATOR: The next one is from Helen Bramswell, Lestat. Please go ahead.

QUESTION: Thanks very much for taking my questions. First off, can I ask, are you folks putting out a press release on this? I mean, this is a lot of data to be giving out without anything to read. It would be very helpful. The next question I want to ask relates to the Hawaiian cluster. I mean, obviously, it was introduced if none of your patients have traveled, so already there was probably one case that you missed, but it must be a larger cluster. From what you described of those people, they weren’t all having sex with one another, so they must have caught it from other people.

(UNKNOWN): Yes. Correct. That’s absolutely correct. And the fact that the medication that we’re using, the dual therapy, is effective, and that most private doctors are not doing cultures would keep it invisible.

QUESTION: Under the radar, right.

(UNKNOWN): And, I’m sorry, we can’t unfortunately hear you very well, Helen, but we will send you a press release, which we have developed and it’s available. And I think the other comment, it’s just that, it’s true that not all gonorrhea cases are diagnosed, only about half, so there is a situation where people can be, essentially become infected with gonorrhea and even spread it to sexual partners without them ever knowing that they had gonorrhea. And then the other thing that Dr. Katz had mentioned is that some people can be diagnosed and treated, but not have their organisms cultured to identify the fact that it was losing susceptibility to our regimen. Are there other questions on the phone?

QUESTION: And that’s …

(UNKNOWN): I’m sorry, Helen, did you want to add another question?

OPERATOR: Give me one moment, I’ll get her back. Okay, go ahead.

QUESTION: Thank you. Can you tell me, are you changing your guidance to physicians as a result of this?

BOLAN: So, this is Dr. Bolan. Currently, we do not think there is enough evidence to change our recommendations or to increase doses based on what we are seeing in the United States and the type of strains that are circling. We are just really wanting people to be aware that we are concerned that it is not going in the right direction; and we will continue to monitor closely. We are also very lucky with our new CARB initiative that we are able to support a more rapid detection system, like Hawaii has, in nine other jurisdictions in the United States. We’ll be doing the E test and seeing if this is a good method for rapid detection and response, as opposed to our traditional surveillance system, which is very good at monitoring, but it takes about two months to get the turnaround time from the islet in the clinic, it goes to the regional lab, it gets verified by the CDC, to come back to the Health Department. That’s too long to really be responding at the local level. So, we are scaling up our detection and response efforts in nine jurisdictions to develop some models that we can then scale up nationally.

QUESTION: That reminds me: Can you tell me when these cases in Hawaii occurred?

BOLAN: We didn’t get that question?

(UNKNOWN): When were the cases in Hawaii?

(UNKNOWN): Oh, the cases in Hawaii were April and May of 2016.

Thank you. All right, go ahead.

QUESTION: If I can ask Dr. Taylor something about the experimental drug, can you give me the name again? I was looking for it on ClinicalTrials.gov and I could not find it? It’s the name that you guys gave?

TAYLOR: The name is ETX0914. I will mention that when this protocol first began, this drug was called AZ0914, it was an AstraZeneca drug. In cases it’s now a subsidiary of AstraZeneca that is focused on antibiotic development, so the drug name has changed and that happened in 2015.

QUESTION: Thank you.

TAYLOR: But ClinicalTrials.gov actually has both on there, but (unintelligible).

(UNKNOWN): The press release also spells that out to make it easier. And there are two other drugs that are in the pipeline that show some promising results, at least in phase two trials for gonorrhea. Thank you. Other questions from the phone?

OPERATOR: There are no others at this time.

(UNKNOWN): Okay. Then I think I’ll conclude the…

(UNKNOWN): Oh, any more on the floor?

(UNKNOWN): No? Okay, I’ll conclude the press conference. Thank you very much for joining.

OPERATOR: That does conclude your conference for today. Thank you for your participation and for using AT&T. You may now disconnect.

(UNKNOWN): Right at the beginning, my phone went off. END