In recent years, the incidence of sexually transmitted diseases has been increasing worldwide and has become a public health problem that seriously endangers human health. Non-gonococcal urethritis and cervicitis are a group of diseases caused by pathogens other than gonococcus infecting the genitourinary system. Chlamydia and mycoplasma are its main common causative agents, and the main clinical manifestations are non-gonococcal urethritis and non-gonococcal cervicitis (mucopurulent cervicitis), which can also cause a variety of diseases and can have serious complications and sequelae. Therefore, effective and rational selection of anti-chlamydial and mycoplasma drugs for treatment is the key to prevention and treatment. This article provides a brief overview of the treatment of non-gonococcal urethritis and cervicitis.
Drug selection
At present, the treatment of Chlamydia trachomatis and mycoplasma mainly uses tetracyclines (including tetracycline, doxycycline, minocycline, etc.), macrolides (including erythromycin, azithromycin, clarithromycin, roxithromycin, cross-fastenomycin, etc.) and quinolones (including ofloxacin, levofloxacin, sparfloxacin, gatifloxacin, moxifloxacin, etc.) drugs. Antibacterial drugs that interfere with cell wall synthesis such as penicillin, cephalosporins, sulfonamides, etc. are not sensitive to mycoplasma, and the killing effect of these drugs on chlamydia is also very weak.
I. Tetracyclines
Tetracyclines are fast-acting antibacterial agents, also have a bactericidal effect at high concentrations, and its mechanism of action is mainly to specifically bind to the bacterial ribosome 30S subunit at the A-position, preventing the amino phthalide-RNA linkage at this position, thus preventing the growth of peptide chains and bacterial protein synthesis; secondly, tetracyclines can cause changes in bacterial cell membrane permeability, so that intracellular nucleotides and other important components leak out, thus Rapidly inhibit the replication of DNA.
1.Doxycycline (Doxycycline)
It is a long-acting, spectral semi-synthetic tetracycline antimicrobial agent, which is produced by deoxygenation of the 6α position of hygromycin. Its antibacterial power is stronger than tetracycline, and slightly weaker than minocycline, good oral absorption, slow excretion, blood concentration maintenance than tetracycline lasting, with high lipid solubility, so strong penetration of tissues. t1/2 is 18-22h, adverse reactions similar to tetracycline, but lighter, and not subject to the image of food. Microorganisms have close cross*resistance to this product with tetracycline and oxytetracycline.
2.Minocycline (Mymanomycin)
It is the 2nd generation semi-synthetic tetracycline drug, similar to the pharmacological effect of tetracycline, but the antibacterial spectrum is broader, sensitive to G+ and G-, especially to tetracycline-resistant strains, and the antibacterial effect on Chlamydia trachomatis is more significant, mainly antibacterial effect, with bactericidal effect at high concentration. The drug is rapidly and completely absorbed orally, and is not imaged by food, t1/2 about 16h, high lipophilicity, easy to penetrate into many tissues and body fluids, so that its concentration in the genitourinary tract is higher than the effective therapeutic concentration, and thus the efficacy is higher. Adverse reactions of minocycline are mainly vertigo and gastrointestinal reactions, which usually appear in the first 3 d after the start of the drug, gradually reduce, and the symptoms disappear after stopping the drug.
Two, quinolones
Quinolones are a class of chemically synthesized drugs with a parent nucleus of 4-quinolones. The antibacterial mechanism is mainly in the cell or mycoplasma DNA helicase, which organizes the functions of DNA replication, repair, chromosome separation and burning, so as to achieve the purpose of sterilization.
1.Levofloxacin
It is the levofloxacin of ofloxacin, and its antibacterial activity is 2 times that of of ofloxacin. It is well absorbed orally, with peak plasma concentration after 1~2h and t1/2 for 6~8h.
2.Sparfloxacin
It is an amino-difluoroquinolone antibiotic, which has a wide antibacterial spectrum and is strong against G- and G+ as well as Chlamydia trachomatis and mycoplasma. It has good permeability to genitourinary tract tissues, and the drug concentration in tissues is several times higher than the simultaneous drug blood concentration. Sparfloxacin introduces fluorine ion in the 8th position so that it is well absorbed in the body, t1/2 in the body up to 15,8-16,9h, can be 1 time / d administration, so the patient compliance is good, and the incidence of adverse reactions is low, but there is photosensitivity, use should avoid sunlight.
3.Gatifloxacin
It is a new spectral and efficient 4th generation quinolone drug, which is a racemic compound of 8-methoxy fluoroquinolones. By inhibiting DNA rotamase and topoisomerase IV, thus inhibiting the replication, transcription and repair of bacterial DNA. The drug is distributed in saliva, semen, prostatic fluid, and lung and kidney tissues. It is well absorbed orally and is not imaged by food factors. The absolute bioavailability is 96% and the peak blood concentration is reached after 1~2h of oral administration.
4.Moxifloxacin
It is the 4th generation of new 8-methoxy fluoroquinolones broad-spectrum efficient antibacterial drugs, with broader spectrum and stronger antibacterial activity than traditional quinolones. Moxifloxacin inhibits both topoisomerase IV and DNA rotamase, remains effective against step 1 mutant strains and is less likely to develop resistance. Resulting in resistance to penicillins, cephalosporins, glycopeptides, macrolides and tetracyclines substrates do not affect the antibacterial activity of moxifloxacin, and there is no cross*resistance between moxifloxacin and these antibacterial agents, and its antibacterial activity is 16 times that of levofloxacin. It is well absorbed orally, food has small image of this product, t1/2 is 2~14h, small adverse reactions, low phototoxicity, good safety and drug resistance.
Third, macrolides
Macrolides are a class of weakly basic antibiotics produced by streptomycin, which act on the 50S subunit of bacterial cell ribosomes and hinder bacterial protein synthesis, and are growth period inhibitors. In recent years, the overuse of this drug has caused an increasing number of drug-resistant strains of bacteria. There is a closer cross*resistance among macrolides.
1.Cross-salicyl
It is a 16-ring macrolide antibiotic with a wide antibacterial spectrum and strong antibacterial activity against G- and G+, mycoplasma and chlamydia, with significant oral absorption and high drug concentration in tissues, much higher in urinary tract and prostate than in blood, t1/2 about 1,7h. The adverse reactions of this product are mainly gastrointestinal reactions. It should be noted that the drug product of cross-sampling is free base, and should be swallowed whole to avoid loss of potency in contact with gastric acid.
2.Clarithromycin
14-membered macrocyclic lactone ring, the 6th position is replaced by methoxy. High stability to gastric acid, high and long-lasting blood concentration after oral administration, absolute bioavailability up to 50% and not subject to food image; strong penetration to tissues and cells; t1/2 is 3-4h, adverse reactions are mainly gastrointestinal reactions, the incidence is about 10,6%; prohibited for pregnant women, not used for children aged <12 years.
3.Roxithromycin
The drug is acid-resistant, good absorption, high blood concentration. Oral single dose of 150mg roxithromycin, 2h plasma concentration peaks, average 0,6-7,9mg/L, its bioavailability is 72%-85%, eating can make bioavailability decreased by 50%, if taken with milk because of the strong fat solubility of this product and good absorption. The distribution in tissues and body fluids is significantly higher than that of erythromycin, but the content in breast milk is very low. The peak blood concentration is 2 times higher than erythromycin, and the absorption rate is not affected by age, the concentration in important tissues and body fluids is higher than serum, and the distribution in the body is wide, t1/2 is 8,4~15,5h, and the adverse reactions are light.
4.Azithromycin
It is inserted 1 methyl-substituted nitrogen in the 9α site of erythromycin endolipid ring, thus producing a 15-membered macrocyclic endolipid, which widens its antibacterial spectrum and enhances its antibacterial activity. The mechanism of action mainly binds to the 50S subunit of the bacterial ribosome and inhibits RNA-dependent protein synthesis (without affecting the synthesis of nucleic acids), thus acting as an antibacterial agent. The drug enters the serum rapidly after oral administration, mostly distributed in the cells, with strong affinity for tissues, tissue concentration is much higher than blood concentration (50 times higher than the maximum plasma concentration), slow excretion, and long tissue t1/2, 35-48h.
Dosing method and precautions
The principles of treatment are early diagnosis, early treatment, timely, adequate and regular medication, and different treatment plans for different conditions. In addition, different treatment plans should be adopted according to the domestic situation. At present, some of the treatment protocols recommended by foreign countries (CDC) are obviously not in line with our national situation, such as the treatment of non-gonococcal urethritis or cervicitis with azithromycin 1g, 1 time dose, which is less used in China. This article only introduces some treatment methods that are widely used in China and have definite efficacy.
I. Treatment of adult infection
1.Tetracyclines
Doxycycline 200mg for the first time and 100mg orally for 2 times/day for 10~14 days.
Minocycline 200mg for the first time and 100mg orally 2 times/day for 10~14 days.
2.Macrolide antibiotics
Erythromycin 500mg, orally, 4 times/day for 10-14 days.
Xanthomycin 200mg, orally, 4 times/day for 10-14 days.
Clarithromycin 500mg, orally, 2 times/day for 10-14 days.
Roxithromycin 150mg, orally, 2 times/day for 10-14 days.
Azithromycin 1g, taken orally, 1h before or 2h after meal.
3.Quinolones
Moxifloxacin 500mg, orally, 1 time/day for 12-14 days.
4.Treatment of mycoplasma, also can apply clindamycin, 150mg-300mg, 3 times/d, 10～14 days.
Second, precautions
1.Tetracyclines as well as quinolones are prohibited for pregnant and lactating women, macrolides can be used, erythromycin or azithromycin is recommended.
2. Tetracyclines such as doxycycline and dimethylaminotetracycline are prohibited under 14 years of age, and quinolones are prohibited under 18 years of age. Children (<45Kg) can use erythromycin 50mg/Kg, d, divided into 4 oral doses, or clindamycin 10-20mg/Kg, d.
3, health education and consultation to improve the patient’s compliance with treatment, strengthen the follow-up review work, the patient’s sexual partner should also receive the same examination or treatment. Avoid sexual intercourse during treatment.
4. In particular, we should remind that the effective antibiotics should be selected according to the local drug sensitivity monitoring results in the areas where they are available. Avoid misuse of antibiotics such as oversized doses and unnecessary multi-drug combinations.
Drug sensitivity and resistance issues
Currently, with the long-term application of a large number of antibiotics, mycoplasma resistance to antibiotics is very common, and there have been reports of various antibiotic-resistant strains, some of which also show multiple drug resistance. Mycoplasma drug susceptibility, i.e., drug resistance, varies from literature to literature. The susceptibility and resistance of pathogens to antibacterial drugs are changing from region to region and year to year. On the other hand, further research on the mechanism of drug resistance and continuous monitoring of drug sensitivity in the region are also necessary for rational drug use.
Treatment of persistent infection or treatment failure
The reasons for treatment failure of non-gonococcal infections include poor patient compliance, low bioavailability of drugs, incorrect dosage regimens and inadequate treatment, misuse of antibiotics, neglect of partner care, false-positive diagnosis, mixed infections, reinfection with residual pathogens in the external genital tract, chronic prolongation, and development of drug-resistant strains.
The presence of Mycoplasma genitalium (Mg) is closely related to the recurrence of UTI, and it has been found that even after antibiotic treatment, 20% to 60% of patients with acute non-gonococcal UTI have persistent or recurrent UTI.
Therefore, for patients with persistent infection or treatment failure, specific causes should be identified and targeted treatment should be given. Sometimes a combination of drugs can be considered. The combination of macrolides and quinolones has been reported to be more effective in China.
Cure criteria and prognosis
The criteria for cure is the disappearance of the patient’s conscious symptoms, no urethral discharge, no white blood cells in the urine sediment, and no chlamydia in the cell picture. The pathogenic microorganism culture is usually not done when judging the cure.
The vast majority of patients with non-gonococcal urethritis and cervicitis have a good prognosis with no serious sequelae or complications after timely, regular and effective treatment.