Innovating with cutting-edge therapies is a priority objective of medicine to face the great challenges in health. Sometimes, however, the solution to some problems is already found in pharmacy drawers and scientific advances actually involve investigating new uses for old molecules. It is the so-called repositioning of medications and this has so far been the best alternative that researchers have found in the face of one of the greatest concerns of international health authorities: the explosion of sexually transmitted infections (STIs), a global phenomenon that punishes Europe with special virulence.
“Doxycycline is an antibiotic used for decades to cure many infections. Now, new research has shown that a 200 milligram pill, used as prophylaxis within 72 hours of risky sexual contact, reduces the possibility of contracting syphilis and chlamydia, two of the most common STIs, by about 80%. And this change in the use of the medication is a substantial advance, because it is the first time that a simple-to-apply pharmacological intervention that prevents these infections that are so common in some groups has been described,” explains Santiago Moreno, head of the Infectious Diseases Service. from the Ramón y Cajal Hospital (Madrid).
Post-exposure prophylaxis with doxycycline, also known as “doxy-PEP”, has recently been a topic of greatest interest at scientific conferences related to STIs. The reason is the unstoppable growth of infections, a phenomenon that the World Health Organization (WHO) and the European Center for Disease Control and Prevention (ECDC) have warned about. Syphilis cases in the EU, for example, grew by 34% in 2022 compared to the previous year, while in Spain the incidence of the disease has multiplied by 10 this century — from 1.77 cases per 100,000 inhabitants in 2000 to 17 .10 in 2022—, according to a recent report from the Ministry of Health.
María del Mar Vera, president of the Study Group on Sexually Transmitted Infections of the Spanish Society of Infectious Diseases and Clinical Microbiology (GeITS-SEIMC), explains that “this global increase has forced the promotion of new preventive strategies and doxycycline offers excellent results. very promising.” However, this expert warns that “the risk of promoting the development of resistance or the possible adverse effects of continued use of this drug” are limitations that require “prudence” before extending the use of doxy-PEP.
Last March, three SEIMC study groups—GeITS, GeSIDA and GEMARA, the latter on antimicrobial resistance—published “a positioning document,” validated by the Ministry of Health, which collects the available scientific evidence and includes some recommendations. According to the text, “the prescription of doxy-PEP will be evaluated only and on an individualized basis in MSM [hombres que mantienen relaciones con hombres] or MTG [mujeres transgénero] “who have sex with men and who have had repeated STIs in the last year.” Taking the pill “should be done as soon as possible after risky” sexual contact, “ideally in the first 24 hours, and never after 72 hours,” the document continues.
The SEIMC groups also insist that “the prevention of STIs through doxy-PEP should not be carried out at the expense of established preventive measures, which is why it is essential to inform the patient about the importance and need to have sexual relations with protection”.
French researchers were the ones who, in 2018, published the first large study on doxycycline as post-exposure prophylaxis to prevent STIs. The work followed 232 participants for 10 months—men who have sex with men and transgender women—users of PrEP, another pill that prevents the spread of HIV if taken before risky sexual relations. This drug has demonstrated great effectiveness in preventing virus infections, but this success has had an undesirable effect: reducing condom use among some groups, which in turn has contributed to the increase in other STIs, agree the experts consulted.
“Research conducted in France and the United States has shown that doxy-PEP achieves an 80% or greater reduction in the risk of contracting syphilis and chlamydia among PrEP users and HIV patients compared to placebo. Against gonorrhea, on the other hand, doxycycline has not been shown to have significant effectiveness, which is surely due to the resistance that the gonococcus [la bacteria que la causa] has already developed,” explains Moreno. Another investigation, carried out in Kenya among women, did not find a significant reduction in this group.
This evidence has opened a debate about the scope that the use of doxy-PEP should have as a public health strategy. The three groups of the SEIMC advocate using it on an individual basis only when there is a history of repeated STIs. “Despite promising results having been obtained in men who have sex with men (MSM) and transgender women (TGW), there are still many unknowns regarding the impact on effects both at the individual level (adverse effects or alteration of the microbiome), and at the population level (selection). and dissemination of antimicrobial resistance)”, states the document.
Some professionals, however, consider that with the available data a further step should be taken. “In recent years we have experienced a change in sexual relationships and dynamics, which today are more open and free. This is a positive thing, but it has had an unintended effect that we must address: the increase in STIs. The question is how we do it. Evidence has shown us for a long time that sticking with condoms as the only strategy does not work. The benefit of doxy-PEP is so powerful that we cannot stop ourselves when implementing it,” defends Jorge García, doctor at the STI Unit of the Drassanes-Vall d’Hebron Center in Barcelona, one of the reference centers in Catalonia.
This position, shared by Moreno, does not deny the risk of the development of resistance, but rather considers it “a hypothesis” that must be monitored. “The results available so far do not show an increase in resistance, so it does not seem to be a sufficient reason to limit access to doxy-PEP,” García insists.
This debate—or the lack of definition about which recommendations to adopt—is repeated at the international level. “There is a certain disparity, but the vast majority of international agencies or scientific societies with the greatest impact advocate not going beyond the use of doxy-PEP in patients with repeated STIs and with medical evaluation on a case-by-case basis. And this is what the document of the three SEIMC study groups defends,” says María del Mar Vera.
Julia del Amo Valero, director of the Division for the control of HIV, STIs, viral hepatitis and tuberculosis of the Ministry of Health, highlights that her department “has collaborated closely with the ECDC, reviewing the scientific evidence to agree on a common position regarding the possible use widespread use of post-exposure prophylaxis with doxycycline in the prevention of syphilis and chlamydia. Following this line, the ministry has collaborated and reviewed the SEIMC document, which has been “shared with the communities within the National Plan against Antibiotic Resistance (PRAN) to work together to address this new preventive strategy and its possible implications. “, Add.
Doxycycline is a so-called tetracycline antimicrobial and has been on the market since the late 1960s. “They were one of the first groups of antibiotics to be discovered and have been used for more than half a century, so we know them well. They are indicated for the treatment of multiple infections, including some STIs, but also respiratory infections, skin infections…”, explains Pablo Caballero, from the scientific dissemination area of the General Council of Official Colleges of Pharmacists.
There are fifteen presentations with this molecule on the market, although almost all of them are 100 milligrams and only one—Proderma 200mg, most commonly used for skin infections—is currently adjusted to the dose of doxy-PEP. Doxycycline, despite being considered a drug without too many side effects, is clearly contraindicated “during pregnancy because it affects the formation of the bones of the fetus,” says Caballero. The drug should also not be used for this reason in children under eight years of age, in whom it can also cause permanent stains on the teeth, a side effect suffered by some people born in the 60s and 70s of the last century and who received this antibiotic in his childhood.
