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Active Ingredient: Tetracycline

Doxycycline is a widely used antibiotic of tetracycline. It is prescribed adults for the treatment of severe microbal diseases on the west market. It has a strong action, and therefore it is not taken by children.

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This review continues a series of publications on well-known "classical" antimicrobial drugs, the use of which in clinical practice acquires a new meaning in the light of the desire to limit the global growth of resistance of infectious agents to antibiotics. For example, Doxycycline is indicated for sexually transmitted infections that do not lose significance, pelvic inflammatory diseases, lower respiratory tract infections, some skin infections, periodontitis. The drug remains relevant for solving complex issues of prevention and therapy of a number of zoonoses (including particularly dangerous infections) and vector-borne diseases, which makes it a strategically important product for healthcare.

Doxycycline, obtained in the 1960s, is a semi-synthetic representative of tetracyclines, one of the most well-known and studied classes of antimicrobial drugs (AMP). The bacteriostatic activity of tetracyclines is due to their binding to the 30S subunit of ribosomes, which leads to a violation of protein synthesis by the microbial cell.

After accumulating a rich clinical experience of the often uncontrolled use of Doxycycline for the widest indications, the drug lost its former popularity against the background of the growth of resistance of pathogens to it and the appearance of younger representatives of other classes of AMP with pharmacodynamic advantages against the background of a better safety profile. An unjustified extrapolation of the frequency and severity of possible adverse drug events (NLAs) of the progenitor of tetracycline to Doxycycline also played an important role, which de facto has the best safety and compliance characteristics due to pharmacokinetic features that allow taking the drug once a day.

However, at present, the global increase in the resistance of pathogens to widely used antibiotics dictates the need to return to the practice of using some classic drugs with preserved activity for appropriate indications. With sexually transmitted infections (STIs), chlamydia and mixed etiology, inflammatory diseases of the pelvic organs (VZOMT) and lower respiratory tract infections that are indisputably relevant today, Doxycycline, including as part of combination therapy, is able to quite successfully solve the problem of atypical pathogens. For acne, rosacea and periodontitis, Doxycycline monotherapy is very effective, which has been shown in a number of qualitative clinical studies. The increasing frequency of tick-borne infections, mainly borreliosis, including for the average polo, makes us recall the high activity of the drug in relation to the causative agent of this disease, which allows the use of Doxycycline for the prevention and therapy of Lyme disease. The migration and tourist flows that have significantly increased in the last decade, as well as the possible threat of bioterrorism, cause interest in Doxycycline as the drug of choice for the treatment and/or prevention of vector-borne diseases and zoonoses (including especially dangerous ones). Next, we will consider special cases of the use of Doxycycline in clinical practice.

Sexually transmitted infections and pelvic inflammatory diseases

Urogenital chlamydia (with its various clinical manifestations, including urethritis, cervicitis, proctitis, venereal granuloma) is the most common STI. Clinical manifestations in the form of mucopurulent discharge from the urethra, cervical canal or rectum serve as the main objective clinical sign of this disease. Due to the presence of frequent gonococcal coinfection, empirical therapy should necessarily be directed at both pathogens. The world's leading and national guidelines on antimicrobial chemotherapy offer Doxycycline as a first-line drug in combination with third-generation cephalosporins (CS) for the treatment of such conditions. In the case of a diagnosed chlamydial monoinfection (for example, venereal granuloma), there is no need for a combination, and the recommended therapy regimen may include only Doxycycline.

It is noteworthy that some recent studies and their systematic reviews have not revealed differences in the equally high (>95%) efficacy and safety of therapy for urogenital chlamydia with Doxycycline, macrolides and fluoroquinolones with similar indicators of resistance of the pathogen to drugs.

VZOMT with clinical forms in the form of endometritis, salpingitis, tubovarial abscess and pelvioperitonitis as a classic example of infections of mixed etiology are often a consequence of the progressive development of gonorrhea and urogenital chlamydia. The etiological difference is only the possible role of the vaginal or intestinal microflora, which dictates the need to include AMP active against such aerobic-anaerobic associations in the therapy regimen. A number of authors also emphasize the possible etiological role of Mycoplasma genitalium. In this regard, the choice of modes of suitable antibacterial therapy (ABT) presents certain difficulties and determines the need for a clear representation of the breadth of the AMP spectrum. Most regimens for the treatment of VZOMT include Doxycycline in combination with inhibitor-protected penicillins (amoxicillin/clavulanate, ampicillin/sulbactam, cefoperazone/sulbactam, piperacillin/tazobactam) or with CS II--IV (cefuroxime, cefoxitin, cefotaxime, cefepim) and metronidazole. Possible alternative regimens include co-administration of Doxycycline with carbapenems (imipenem, meropenem) or fluoroquinolones (ciprofloxacin) and metronidazole. And again, by analogy with chlamydia, various treatment regimens of VZOMT, including Doxycycline or modern macrolide, have no significant differences in effectiveness.

Infectious complications of spontaneous and artificial abortions are etiologically identical to the VZOMT. Nevertheless, aerobic-anaerobic associations of the vaginal and intestinal microflora with a high probability of the presence of gonococci and/or chlamydia play a dominant role here. That is why their ABT regimens are absolutely similar and include Doxycycline.

Alternative regimens (for penicillin intolerance) ABTS of primary and secondary syphilis also include Doxycycline. Doxycycline as the drug of choice may be recommended for the treatment of inguinal granuloma (donovanosis), the causative agent of which is Klebsiella granulomatis (formerly known as Calymmatobacterium granulomatis).

A special topic is the prevention of infections during artificial termination of pregnancy. Despite the fact that currently the frequency of infectious complications after surgical abortions is low, the consequences of their development can be extremely severe. It is known that concomitant urogenital infection increases the risk of such complications by two times. Oral administration of Doxycycline at a dose of 200 mg in a twelve-hour interval before abortion significantly reduces the risk of developing VZOMT both in the case of the initial presence and absence of infection.

Skin and soft tissue infections

The causes of acne (acne) are still not clearly defined. In the pathogenesis of the disease, an important role is assigned to both non-infectious causes - seborrhea, and an infectious agent - the bacterium Propionibacterium acnes. That is why local and systemic ABT plays an important role in the complex treatment of this pathological condition. For systemic therapy in moderate to severe forms of acne, the drug of choice is Doxycycline. Due to the high risk of relapse, the duration of antibiotic use can vary significantly, sometimes reaching several months.

The high clinical efficacy of Doxycycline has also been confirmed in recent comparative studies. Thus, comparable efficacy and safety of systemic acne therapy regimens was demonstrated, including 3-month daily use of Doxycycline or azithromycin (intermittent course). In one of the studies, the authors came to an interesting conclusion that Doxycycline is significantly more effective than azithromycin in patients older than 18 years [21, 22]. Recent reviews of the efficacy and safety of tetracyclines in systemic acne therapy also confirm the low incidence of Doxycycline compared to tetracycline and minocycline.

Rosacea (pink acne) is the next urgent problem of dermatology. By analogy with vulgar acne, the etiopathogenesis of this disease is an even greater mystery. Non-infectious causes of skin inflammation play a major role, nevertheless, among pharmacotherapeutic agents, a distinct positive and persistent therapeutic effect is noted only with the systemic use of certain antibiotics (tetracyclines, macrolides), which may well be associated with non-antibacterial effects of these classes of AM.

Tetracyclines have been used for systemic therapy of rosacea for more than 40 years. An important fact is the approval of Doxycycline by the FDA (US Food and Drug Administration) for the treatment of this disease. The effectiveness of the drug has also been confirmed by experts of the Cochrane Collaboration. The duration of therapy with Doxycycline at a dose of 40 to 100 mg / day may be 3 months. The available results of studies on the use of Doxycycline in comparison with clarithromycin and azithromycin demonstrate the absence of a significant difference in efficacy and safety at the end of 2- and 3-month courses of therapy, respectively.

Cat scratch disease and soft tissue infections after a cat bite are caused by rare human pathogens of the genus Bartonella (B. henselae, B. quintana) and Pasteurella multocida, respectively. These pathogens are characterized by sensitivity to a few classes of AMP, among which are tetracyclines, as a result of which Doxycycline is an alternative drug for therapy.

Vector-borne diseases, zoonoses and especially dangerous infections

Almost the entire territory is inhabited by ixode mites, which are carriers of pathogens of severe human diseases. According to Rospotrebnadzor, recently there has been an increased activity of ticks, which is why cases of bitten people seeking medical help have become more frequent. If in Siberia and the Far East it is absolutely necessary, first of all, to remain vigilant because of the possible transmission of tick-borne encephalitis virus by these arthropods due to the endemicity of the area, then in the middle zone it should not be forgotten that ticks are also carriers of not so dangerous, but rather difficult to diagnose and treat infections. We are talking about ixodic tick-borne borreliosis (Lyme disease), monocytic human ehrlichiosis and ixodic granulocytic human anaplasmosis. To indicate the urgency of the problem, it should be mentioned that the causative agents of these infections, which are obligate intracellular pathogens, were discovered and described a little more than two decades ago.

The epidemiological situation of infection of ticks with pathogens of the above diseases, of course, may differ in different regions. On the territory of the Moscow region, for example, about 20% of ticks are infected with pathogenic borrelia (up to 45% in some areas), ehrlichia can be found in 10% of Ixodes persulcatus individuals and anaplasma in 6% of Ixodes ricinus individuals. Cases of mixed infection of one individual with various pathogens are not uncommon. About 500 cases of tick-borne borreliosis are registered annually.

The causative agent of Lyme disease is Borrelia burgdorferi (its various genovids). In the acute period, the pathognomonic symptom is ring-shaped migrating erythema, which may be absent in a third of cases. With the development of the disease and its transition to a chronic form, lesions of the joints, nervous system (meningitis, facial nerve paralysis), eyes, and heart occur.

Monocytic human ehrlichiosis is caused by the bacteria Ehrlichia chaffensis and Ehrlichia muris. As in the case of borreliosis, the incubation period is on average 2 weeks. The disease is characterized by an acute onset with fever, myalgia and other nonspecific symptoms. Jaundice-free hepatitis and kidney damage are not uncommon.

Ixodic granulocytic anaplasmosis in humans is caused by the bacterium Anaplasma phagocytophillum (formerly known as Ehrlichia phagocytophilla). Acute onset (on average 2 weeks after the bite) and nonspecific symptoms may also be accompanied by the development of liver and kidney damage.

The best method of preventing these diseases is undoubtedly measures aimed at preventing tick bites. First of all, these are the rules of behavior in the zone of their possible habitat, the type of clothing, the use of repellents [33]. In case of detection of a tick attached to the body, the latter should be carefully removed according to a special technique, trying not to leave parts of the tick's mouth apparatus in the skin and avoiding pressure on its abdomen. The best scenario for the development of events is the transfer of the extracted tick to the Rospotrebnadzor laboratory (or another one that has the necessary capabilities) to determine infection with human pathogens. Upon receiving a positive response, prevention is carried out by various AMPS, including Doxycycline.

Pathogenic borrelia, ehrlichia and anaplasmas are sensitive to Doxycycline, which is a first-line drug for the prevention and therapy of infections caused by them. Within 72 hours after the bite, in order to effectively prevent Lyme disease, adults need to take the drug once at a dose of 200 mg, for children over 8 years of age, the dose is 4 mg / kg of weight (but not more than 200 mg). Despite the fact of prevention, the period of observation of patients for possible development of the disease is 30 days.

For the treatment of early localized (ring-shaped erythema) or early disseminated forms (without neuroborreliosis or heart damage) of Lyme disease, the period of taking Doxycycline (200 mg / day for two doses) can be from 10 to 21 days. Children over 8 years of age can receive the drug at a dose of 4 mg / kg per day (but not more than 200 mg), divided into two doses. With the development of symptoms of damage to the nervous system, Doxycycline, which has good bioavailability, can be taken in a daily dose of 200-400 mg for two doses for 10 to 28 days. For children over 8 years of age, the dose is calculated based on 4--8 mg / kg per day, divided into two doses (no more than 200 mg per dose). Patients with heart disease are subject to hospitalization. Parenteral ceftriaxone is recommended for therapy, however, with the resolution of symptoms of atrioventricular block, therapy may well continue with Doxycycline at a dose of 200 mg / day.

With some manifestations (arthritis, chronic atrophic acrodermatitis) of the late form of Lyme disease, Doxycycline is prescribed to patients in the usual dose (by analogy with early form therapy) for 3-4 weeks.

In patients with suspected granulocytic anaplasmosis, therapy should be started immediately, without waiting for positive results of serological diagnosis in order to avoid the development of severe complications. Acute onset with unexplained fever, chills, platelet and leukopenia, increased liver enzymes in patients with tick bite in the previous 3 weeks. they are indications for the appointment of Doxycycline. The usual dose for adults is 100 mg twice a day for 1 month. Fever lasting more than 48 hours while taking Doxycycline is a sign that excludes anaplasmosis with the need for further diagnostic search. It is easy to see that the proposed regimen is also adequate for the treatment of borreliosis in the case of coinfection. The dose of Doxycycline for children older than 8 years is 4 mg / kg per day for two doses (but not more than 100 mg at a time), but the duration of therapy can be only 10 days.

As in the previous case, ABT of monocytic ehrlichiosis should be initiated if the disease is suspected in patients with a history of tick bite even before receiving the results of serological diagnosis in order to avoid severe complications. Doxycycline is the drug of choice at a dose of 100 mg twice a day for 5-14 days for adults. For children over 8 years of age, the recommended dose is 4.4 mg / kg per day, divided into two doses. The absence of positive dynamics against the background of taking Doxycycline determines the need for further diagnostic search. Interestingly, due to the potential danger of ehrlichiosis and anaplasmosis for life, the Committee on Infectious Diseases of the American Academy of Pediatrics considers it possible to prescribe Doxycycline to children of any age, emphasizing the minimal risk of tooth discoloration due to taking short courses of the drug.

Brucellosis caused by several types of brucella (Brucella spp.) is one of the most common zoonoses and is a problem for health care not only in developing countries. Every year, about half a million cases of brucellosis are registered in the world, reaching a frequency of 1 per 1,000 in endemic areas. ABT of acute and chronic forms of the disease aims not only to cure infection, but also to prevent relapses, as well as possible severe complications from the musculoskeletal system, cardiovascular, central nervous and reproductive systems.

Historically, it has been established that monotherapy of brucellosis is accompanied by an unacceptably large number of relapses, therefore, currently it is proposed to use combinations of 2-3 drugs for successful treatment. Moreover, a recent meta- and systematic analysis of studies on the effectiveness of various ABT regimens of brucellosis has shown its significant difference. In general, therapy regimens, including Doxycycline and aminoglycoside, are characterized by high efficiency. Triple therapy – Doxycycline + rifampicin + aminoglycoside (gentamicin or streptomycin) has advantages over the Doxycycline + streptomycin regimen in terms of the risk of relapse (HR = 2.5; CI 95% 1.26--5.0). Therapy for 6 weeks or more also has advantages over short courses of antibiotic prescribing.

Leptospirosis caused by spirochaetes of the genus Leptospira is a widespread zoonosis, especially in countries with developed animal husbandry. However, outbreaks of this disease, as well as sporadic cases, are not always the result of mandatory direct contact with animals in natural focal zones. The waterway of transmission involves the use of contaminated water and bathing in reservoirs, as well as force majeure, such as floods. There are 13 serological groups of L.interrogans circulating, which cause jaundice and non-jaundice forms of the disease. Doxycycline is the drug of choice for the treatment of leptospirosis at a dose of 100 mg twice a day for 7 days.

The issue of antibacterial prevention of leptospirosis remains open. Despite the fact that one qualitative study showed the effectiveness of prophylactic administration of doxycillin at a dose of 200 mg once a week, the experts of the Cochrane Collaboration, when conducting a systematic analysis, only emphasize the possible effectiveness of this regime for people who are in an endemic area for a short time, rather than for the permanent population.

Rickettsias are caused by a wide range of potentially lethal fevers and typhus with a transmissible (fleas, lice, ticks) transmission mechanism. Common clinical manifestations of Rocky Mountain spotted fever, Tsutsugamushi fever, typhus and other rickettsioses are acute onset, fever and a rash of different characteristics. All types of rickettsias are highly sensitive to tetracyclines, which is why Doxycycline is the drug of choice for therapy at a daily dose of 200 mg for two doses (2.2 mg / kg for children over 8 years old) for 3-14 days (or for another 2 days after normalization of body temperature).

Since the late 1970s, no cases of plague have been registered in the Territory. At the same time, cases of infection occur annually in neighboring countries of the Asian region and in African countries. In addition, a large number of Yersinia pestis strains are circulating in natural foci on the territory of the South Caucasian republics. High contagiousness and mortality in cases of plague cause the attitude to the plague as a particularly dangerous infection that needs, in addition to ABT, thorough and large-scale anti-epidemic measures [47]. In addition to the natural ways of plague infection in endemic areas, we should not forget about the potential for the use of more virulent strains of the pathogen as biological weapons and in terrorist attacks.

Conducting qualitative comparative studies of the effectiveness of AMP in particularly dangerous infections is extremely difficult for obvious reasons. Nevertheless, tetracyclines have good clinical efficacy along with aminoglycosides, chloramphenicol, trimethoprim/sulfomethoxazole and ciprofloxacin. Parenteral or oral Doxycycline is prescribed at a dose of 200 mg / day for two doses, the duration of therapy is 10 days. For emergency prevention, oral forms of Doxycycline are prescribed in a similar mode to those in contact. For children over 8 years of age, the daily dose for prevention and treatment is 5 mg / kg in 2 doses.

The causative agent of anthrax, which occurs in the natural path of infection (more often from sick, fallen cattle or through infected products of their processing), mainly in the form of a skin form, is Bacillus anthracis. In this case, skin defects serve as the entrance gate for extremely resistant spores in the external environment. Highly lethal generalized forms of the disease - pulmonary, oropharyngeal, gastrointestinal or meningial - occur when the pathogen is used as a biological weapon or in terrorist attacks.

Fortunately, the vegetative forms of the pathogen are sensitive to drugs such as penicillin, Doxycycline and ciprofloxacin, which is why they are used for the prevention and treatment of the disease. In severe cases, combinations of these drugs with rifampicin or vancomycin can be used. The use of AMP leads to rapid eradication of the pathogen, however, it must be remembered that the characteristic necrotic skin manifestations of infection resulting from the action of the toxin can persist for several weeks, which should not serve as a reason for prolongation of ABT. The usual duration of therapy for uncomplicated cutaneous form of anthrax is 3-7 days, and generalized forms – 10-14 days.

The World Health Organization recommends long-term antibacterial prophylaxis of anthrax only in a single case - in persons who have been found (or with a high degree of probability) intentionally exposed to inhalation exposure to a high concentration of pathogen spores (i.e., in fact, only in the case of the use of bacteriological weapons or a terrorist attack). In such cases, Doxycycline at a dose of 100 mg twice a day (for children older than 8 years - 2.5 mg / kg twice a day) should be taken for 2 months. The duration of preventive use of AMP for such a long time is determined by the possibility of preserving the pathogen spores in the lung tissues. Simultaneous start of prophylactic antibiotics with vaccination involves reducing the preventive course to 6 weeks. [48]. The reasoned conclusions of some authors are interesting that with the equal effectiveness of Doxycycline and ciprofloxacin for the prevention and treatment of anthrax in mass infection, the preferred choice of Doxycycline is justified by its significantly lower (in comparison with ciprofloxacin) cost.

Imported cases of malaria are reported annually with a relatively high frequency. So, in 2007, 128 cases of this infection were registered, in the structure of which 36% was tropical malaria (in two cases fatal). This situation is undoubtedly due to the increased tourist flows to the countries of Southeast Asia (mainly India and directly the state of Goa). In this regard, Rospotrebnadzor regularly conducts preventive and explanatory work both with representatives of the tourism industry and with persons directly traveling to countries with a tropical climate.

Certain types of plasmodium (P. vivax, P. falciparum, P. malariae, P. ovale) cause various nosological forms of malaria, characterized by a cyclical recurrent course with a change of acute febrile and intercostal states, hepatosplenomegaly and anemia. It is noteworthy that infection can occur with just one bite by a mosquito of the genus Anopheles. Under certain circumstances (absence, intolerance to antimalarial drugs or resistance to parasites) Doxycycline can be a drug for the prevention and therapy of malaria.

For the treatment of uncomplicated malaria, Doxycycline is used in a daily dose of 1.5 mg / kg for a week and only in combination with quinine. Individual prevention of plasmodium infection is carried out with Doxycycline according to the scheme of 100 mg / day once (1.5 mg / kg for children over 8 years old), and the drug should be started just one day before arrival in the endemic area, which distinguishes the scheme from similar ones for antimalarial drugs. The need to take Doxycycline persists throughout the entire stay in a disadvantaged area, as well as for 4 weeks after returning.

A systematic analysis of the preventive use of Doxycycline has shown its high effectiveness on a par with antimalarial drugs with a lower or equal frequency of NLA. It was found that the frequency of infection of persons staying in endemic territories for a long time (up to 20 weeks) when taking Doxycycline was 2-3%, while when taking placebo, the occurrence of the disease was noted in 35-77% of cases.

Periodontal infections

In periodontitis, gram-negative anaerobes and spirochetes predominate in adults, among which Porphyromonas gingivalis, Bacteroides forsythus, Actinobacillus actinomycetemcomitans and Treponema denticola are most often distinguished. In adolescence, the usual pathogens are A. actinomycetemcomitans and Capnocytophaga spp. These microorganisms are characterized by high aggressiveness and the ability to penetrate into periodontal tissues with the destruction of its collagen fibers, which is the main link in the etiopathogenesis of rapidly progressing forms of periodontitis. That is why adequate treatment of rapidly progressing forms of periodontitis should be comprehensive, including standard dental mechanical treatment procedures (scaling and polishing of roots) and systemic ABT.

The use of tetracyclines for the treatment of periodontitis has pharmacodynamic and unique pharmacokinetic prerequisites. In addition to the sensitivity of periodontal pathogens to tetracyclines, it was found that the concentrations of this class of AMP in the crevicular (gingival) fluid are several times higher than serum concentrations, which is a predictor of their high efficiency. So, the concentration of Doxycycline in the gingival fluid after taking 200 mg on the first day and 100 mg in the following reaches an average of 6 micrograms / ml.

A systematic analysis of studies on the effectiveness of systemic administration of antibiotics for periodontitis shows that such ABT, in addition to dental procedures or without them, can positively affect the course of rapidly progressive, chronic and recurrent forms of the disease [56]. In one of the comparative studies of the effectiveness of Doxycycline and the combination of amoxicillin with metronidazole in localized rapidly progressing periodontitis, the same improvement in clinical parameters in both groups of patients and persistent eradication of A. actinomycetemcomitans for 90 days of observation.

Respiratory tract infections

Since its discovery and for decades, Doxycycline has been actively used for the treatment of respiratory tract infections (IDP). However, at the end of the last century, due to the global problem of the growth of resistance of pneumococci (the main causative agent of IDP) to various classes of AMP (including tetracyclines), the place of the latter underwent a critical reassessment. Currently, the resistance of pneumococci to tetracycline is more than 25%, which does not allow it to be used as a drug of choice and for the treatment of infections of this etiology. At the same time, it is known that in the case of community-acquired pneumonia (VP), against the background of about half of cases of unidentified etiology, S. pneumoniae is an etiologically significant agent only in ~14%, whereas up to a third of all cases are caused by so-called atypical pathogens, which makes them the object of etiotropic therapy.

Thus, Doxycycline as monotherapy can be prescribed to patients with VP if there are strict suspicions that chlamydia or mycoplasma caused this disease. The ineffectiveness of the initial treatment regimen with beta-lactams or inhibitor-protected penicillins is a reason to reconsider the choice of AMP or the addition of a drug active against atypical pathogens to the treatment regimen, for example, Doxycycline.

Gastrointestinal tract infections

One of the causes of watery diarrhea may be Vibrio colerae. Isolated cases of cholera imported from the countries of Southeast Asia, Africa and Latin America are periodically recorded. The main method of preventing this potentially lethal disease is to observe hygiene measures and nutrition rules in endemic areas aimed at interrupting the fecal-oral mechanism of transmission of the pathogen. Cholera vibrio remains sensitive to many AMPS, including Doxycycline, a single dose of which at a dose of 300 mg leads to rapid clinical and bacteriological recovery. It should be noted that according to the WHO, in 80% of cholera cases, only adequate rehydration is necessary and sufficient for treatment.

Relatively infrequently, the symptoms of infectious diarrhea can also cause infection with Yersinia enterocolitica. A variant of the disease with a possible lesion of the mesentery lymph nodes (mesadenitis) can lead to the development of a clinical picture very similar to acute surgical infections [63]. Mild and moderate cases of the abdominal form of the disease have a tendency to self-resolution, however, in the case of a serious condition of the patient and / or the development of bacteremia, the appointment of AMP is mandatory. Doxycycline may be the drug of choice for therapy at a standard daily dose of 200 mg for 5 days.

Conclusion

Despite the fact that the practice of using Doxycycline for the treatment of infections has been going on for many decades, the drug continues to be in demand for the treatment of a wide range of topical, socially significant and especially dangerous human diseases. Against the background of the lack of significant progress in the emergence of new AMP, the activity of the drug against atypical pathogens can be successfully implemented for mono- and/ or complex therapy of STIs, VZOMT, IDP. Against the background of an ever-increasing frequency of vector-borne infections and an increase in migration flows, Doxycycline is becoming in demand, including for the treatment and prevention of rare, insufficiently studied, as well as particularly dangerous infections. The latter is especially important at the present time in the light of the palpable threat of the use of biological weapons and terrorist attacks.

The half-century history of Doxycycline determines the totality of its positive characteristics in terms of comprehensive study and predictability of the development of relatively non-severe NS. The best safety profile among tetracyclines, the presence of soluble dosage forms of Doxycycline monohydrate with improved pharmacokinetics and tolerability are additional advantages of the drug. The low cost of Doxycycline and the availability of its high-quality generics on the market is also a boon for countries with a permanent health budget deficit.