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*Only for medical professionals to read the reference medication prescription, waiting for you to see the daily work of the outpatient pharmacy includes reviewing prescriptions and dispensing prescriptions.
The review of prescriptions is a test of the professional skills of the outpatient dispensing pharmacist
.
The following scenario seems to be happening every day in the clinic: Dispensing pharmacist: Your prescription is unreasonable and needs to be returned.
A single dose of azithromycin tablets is too large
.
Doctor: I considered that this patient had nongonococcal urethritis caused by mycoplasma and chlamydia, so I used a single dose of azithromycin tablets
.
What's going on? Let's take a look at this prescription for doctors and pharmacists with Jie Xiaoyao
.
Scan the code to read the detailed medication instructions for azithromycin tablets.
Is it because the doctor's prescription is not appropriate or is the pharmacist's excessive intervention? The discussion is as follows: 1.
What is non-gonococcal urethritis? Non-gonococcal urethritis (NGU) refers to urethritis caused by sexual contact, mainly caused by chlamydia and mycoplasma infection, and a few can be caused by infection by some other pathogens
.
According to the 2016 Expert Consensus on Diagnosis and Treatment of Mycoplasma Infection in the Genital Tract, it is currently believed that 35% to 50% of urethritis caused by non-gonococcal urethritis is related to chlamydia infection, 20% to 40% is related to mycoplasma, and the other causes are still unclear
.
Ureaplasma urealyticum (Uu) and Mycoplasma genitalium (Mg) have been shown to be the pathogens of male nongonococcal urethritis
.
The main manifestations are urethral discomfort, dysuria, or urethral secretions.
The symptoms of dysuria are relatively mild.
Sometimes only mild tingling and itching sensation in the urethra.
The urethral secretions are mucous or mucopurulent, thinner and less in quantity [ 1]
.
2.
How much do you know about Azithromycin? Azithromycin (AZM) is a macrolide antibacterial drug, which has the advantages of short course of treatment, good tolerability, good compliance, fewer contraindications or fewer adverse reactions
.
It has unique pharmacokinetic properties, strong antibacterial activity against atypical pathogens, and good post-antibiotic effects, high concentration in tissues and long half-life [2]
.
The mechanism of action is to bind to the 23S rRNA of the 50S ribosomal subunit of sensitive bacteria, thereby inhibiting bacterial protein synthesis and preventing the composition of the 50S ribosomal subunit
.
3.
The treatment of non-gonococcal urethritis 1.
The azithromycin drug instruction [indications] column lists the drug indications of azithromycin, including "urethritis and cervicitis caused by Chlamydia trachomatis or Neisseria gonorrhoeae", The corresponding specific medication plan is explained in the column of 【Usage and Dosage】
.
Screenshot of the instruction manual 2.
In the "National Guidelines for Antimicrobial Diagnosis and Treatment (Second Edition)", it is recommended that azithromycin is the first choice for the treatment of genital tract Chlamydia trachomatis infection, and the recommended usage is 1g single dose
.
Guide screenshot 3, 2016 "Expert Consensus on the Diagnosis and Treatment of Mycoplasma Genitalia Infection"[3] treatment recommendations: The common treatment for mycoplasma infection in the genitourinary tract is: doxycycline 100mg po bid, 7 days; azithromycin 1g, single oral administration , Or 0.
25g qd po, double the first dose, 5-7d in total; levofloxacin 500mg po qd, 7d; moxifloxacin 400mg po qd, 7-14d
.
If the patient has pelvic inflammatory disease, he needs to be treated according to the pelvic inflammatory treatment plan, and the total course of treatment is 14 days
.
Screenshot of the guideline There are instructions in the instructions, as well as the recommendations of China's "Expert Consensus on the Diagnosis and Treatment of Mycoplasma Genitalia" and the "National Guidelines for Antimicrobial Diagnosis and Treatment (Second Edition)"
.
It is reasonable for a single dose of azithromycin to treat nongonococcal urethritis .
4.
Azithromycin is enough? Which is the most suitable drug to treat NGU? Research reports on mycoplasma resistance to macrolide antimicrobials are not uncommon
.
Data [4] showed that the mutation rates of MG macrolide and quinolone resistance-related genes (23SrRNA and parC) in male Mycoplasma genitalium (MG)-positive urethritis patients in the STD clinic in Nanjing from 2011 to 2015 were as high as 89%
.
In a national survey in Denmark, 31,600 samples were tested for Mycoplasma genitalium
.
It was found that the drug resistance rate of macrolides was 38% (385/1008) [5]
.
The results of a systematic review of 21 clinical studies published in Clin Infect Dis showed that the clinical cure rate of azithromycin single-dose therapy, the conventional treatment regimen, dropped from 85% reported in 1999-2008 to 67% in 2009-2013.
.
In 2013, the results of a randomized controlled trial published on Clin Infect Dis showed that the current clinical cure rate and microbiological cure rate of NGU are low, and the treatment failure of Mycoplasma genitalium is extremely common, and there is no significant difference between azithromycin and doxycycline [ 6]
.
In 2021, The New England Journal of Medicine published a randomized, double-blind, controlled clinical trial aimed at comparing the efficacy of single-dose azithromycin and doxycycline 7-day therapy in the treatment of men with male-to-male chlamydia infection.
Experiment
.
It was found that the 7-day therapy effect of doxycycline was better than that of a single dose of azithromycin
.
This article discusses the reasons for this difference in treatment course, which may be related to the following aspects: First, the minimum inhibitory concentration (MIC) of azithromycin against chlamydia in colorectal cell lines is 4 times higher than that in cervical cell lines, while doxycycline There is no difference in the MIC of chlamydia in the two cell lines
.
Secondly, doxycycline is highly fat-soluble, which is conducive to the rapid diffusion of the drug to the infected site; while azithromycin is also fat-soluble, but it is mainly transported through inflammatory cells.
If the immune response to Chlamydia rectal infection is weakened, then This may reduce the dose of azithromycin transported to the site of infection, thereby affecting the efficacy [7]
.
In the "National Guidelines for Antimicrobial Diagnosis and Treatment (Second Edition)", it is pointed out that when considering the epididymal-orchitis caused by Mycoplasma trachomatis, the first choice is not azithromycin, but ceftriaxone + doxycycline
.
Screenshot of the guidelines In 2020, there is a review of the introduction of the guidelines for the diagnosis and treatment of Mycoplasma genitalium infection in Europe, Australia, and the United Kingdom [8].
The article lists the use of azithromycin in foreign guidelines.
It has been tested for macrolide resistance sites and is not resistant.
European guidelines, the recommended first-line treatment plan is azithromycin 5-day therapy (total dose 1.
5g) or josamycin; Australian and British guidelines both recommend sequential treatment with doxycycline pretreatment, but follow-up azithromycin The course of treatment and dosage are slightly different.
The Australian guidelines recommend a 4-day course of treatment with a total dose of 2.
5g, and the British guide recommends a 3-day treatment with a total dose of 2g
.
An Australian study showed that sequential treatment with doxycycline and azithromycin can clear 94.
8% of macrolide-sensitive MG infections
.
It can be seen that none of the three guidelines recommends a single use of azithromycin
.
Screenshot of the guideline In the "Guidelines for the Diagnosis and Treatment of Syphilis, Gonorrhea, and Genital Chlamydia Trachomatis Infection (2020)", the recommended treatment for adult Chlamydia trachomatis infection is azithromycin or doxycycline, non-sequential treatment, and the total dose of azithromycin is the total dose The 2.
0g 3-day therapy is similar to the UK
.
Screenshot of the guideline Therefore, as the resistance of Mycoplasma genitalium to macrolide drugs intensifies, azithromycin is no longer the first choice for treatment, and the failure rate of azithromycin 1.
0g single dose or increased dose is still high
.
In the case of treatment failure, the bacterial load is low, so sequential or combined treatment with an antibacterial drug can be considered, with one antibacterial drug to reduce the bacterial load, while cooperating with another antibacterial drug to improve the efficacy
.
5.
Summarize and analyze the reason why the prescription dose is considered unreasonable by the pharmacist, perhaps because the cognition of azithromycin is still based on the basic cognition of "eat three stop four" and "first 500mg, maintain 250mg"
.
This also reminds us pharmacists that it is very important for our daily work to strengthen our understanding of the sensitivity of pathogenic microorganisms and to further increase our attention to clinical research
.
This time the prescription challenge, is it correct that the doctor insists on the single-dose azithromycin treatment, or is the pharmacist requesting the return of the prescription? Talk about your views in the comment section! References: [1] STD Control Center of Chinese Center for Disease Control and Prevention, STD Group of Chinese Medical Association Dermatology Branch, STD Sub-Professional Committee of Dermatologist Branch of Chinese Medical Doctor Association.
Guidelines for the diagnosis and treatment of syphilis, gonorrhea and genital tract Chlamydia trachomatis infection ( 2020)[J].
Chinese Journal of Dermatology, 2020, 053(003):168-179.
[2]Li W,Hui-Yan C.
Pediatric Clinical Pharmacology(PEOPLE'S MEDICAL PUBLISHING HOUSE Co.
, LTD, Beijing,2015 ).
[3]Zhang Dai, Liu Zhaohui.
Expert consensus on diagnosis and treatment of mycoplasma infection in the genital tract[J].
Chinese Journal of Sexuality, 2016, 025(003):80-82.
[4]Li Y, Su X, Le W, et al.
Mycoplasma genitalium in Symptomatic Male Urethritis: Macrolide Use Is Associated With Increased Resistance[J].
Clinical Infectious Diseases, 2020, 70(5):805-810.
[5]Salado-Rasmussen, Kirsten, Jensen, et al.
Mycoplasma genitalium Testing Pattern and Macrolide Resistance: A Danish Nationwide Retrospective Survey.
[J].
Clinical Infectious Diseases, 2014.
[6]Manhart LE, Gillespie CW, Sylvan LM, et al.
The review of prescriptions is a test of the professional skills of the outpatient dispensing pharmacist
.
The following scenario seems to be happening every day in the clinic: Dispensing pharmacist: Your prescription is unreasonable and needs to be returned.
A single dose of azithromycin tablets is too large
.
Doctor: I considered that this patient had nongonococcal urethritis caused by mycoplasma and chlamydia, so I used a single dose of azithromycin tablets
.
What's going on? Let's take a look at this prescription for doctors and pharmacists with Jie Xiaoyao
.
Scan the code to read the detailed medication instructions for azithromycin tablets.
Is it because the doctor's prescription is not appropriate or is the pharmacist's excessive intervention? The discussion is as follows: 1.
What is non-gonococcal urethritis? Non-gonococcal urethritis (NGU) refers to urethritis caused by sexual contact, mainly caused by chlamydia and mycoplasma infection, and a few can be caused by infection by some other pathogens
.
According to the 2016 Expert Consensus on Diagnosis and Treatment of Mycoplasma Infection in the Genital Tract, it is currently believed that 35% to 50% of urethritis caused by non-gonococcal urethritis is related to chlamydia infection, 20% to 40% is related to mycoplasma, and the other causes are still unclear
.
Ureaplasma urealyticum (Uu) and Mycoplasma genitalium (Mg) have been shown to be the pathogens of male nongonococcal urethritis
.
The main manifestations are urethral discomfort, dysuria, or urethral secretions.
The symptoms of dysuria are relatively mild.
Sometimes only mild tingling and itching sensation in the urethra.
The urethral secretions are mucous or mucopurulent, thinner and less in quantity [ 1]
.
2.
How much do you know about Azithromycin? Azithromycin (AZM) is a macrolide antibacterial drug, which has the advantages of short course of treatment, good tolerability, good compliance, fewer contraindications or fewer adverse reactions
.
It has unique pharmacokinetic properties, strong antibacterial activity against atypical pathogens, and good post-antibiotic effects, high concentration in tissues and long half-life [2]
.
The mechanism of action is to bind to the 23S rRNA of the 50S ribosomal subunit of sensitive bacteria, thereby inhibiting bacterial protein synthesis and preventing the composition of the 50S ribosomal subunit
.
3.
The treatment of non-gonococcal urethritis 1.
The azithromycin drug instruction [indications] column lists the drug indications of azithromycin, including "urethritis and cervicitis caused by Chlamydia trachomatis or Neisseria gonorrhoeae", The corresponding specific medication plan is explained in the column of 【Usage and Dosage】
.
Screenshot of the instruction manual 2.
In the "National Guidelines for Antimicrobial Diagnosis and Treatment (Second Edition)", it is recommended that azithromycin is the first choice for the treatment of genital tract Chlamydia trachomatis infection, and the recommended usage is 1g single dose
.
Guide screenshot 3, 2016 "Expert Consensus on the Diagnosis and Treatment of Mycoplasma Genitalia Infection"[3] treatment recommendations: The common treatment for mycoplasma infection in the genitourinary tract is: doxycycline 100mg po bid, 7 days; azithromycin 1g, single oral administration , Or 0.
25g qd po, double the first dose, 5-7d in total; levofloxacin 500mg po qd, 7d; moxifloxacin 400mg po qd, 7-14d
.
If the patient has pelvic inflammatory disease, he needs to be treated according to the pelvic inflammatory treatment plan, and the total course of treatment is 14 days
.
Screenshot of the guideline There are instructions in the instructions, as well as the recommendations of China's "Expert Consensus on the Diagnosis and Treatment of Mycoplasma Genitalia" and the "National Guidelines for Antimicrobial Diagnosis and Treatment (Second Edition)"
.
It is reasonable for a single dose of azithromycin to treat nongonococcal urethritis .
4.
Azithromycin is enough? Which is the most suitable drug to treat NGU? Research reports on mycoplasma resistance to macrolide antimicrobials are not uncommon
.
Data [4] showed that the mutation rates of MG macrolide and quinolone resistance-related genes (23SrRNA and parC) in male Mycoplasma genitalium (MG)-positive urethritis patients in the STD clinic in Nanjing from 2011 to 2015 were as high as 89%
.
In a national survey in Denmark, 31,600 samples were tested for Mycoplasma genitalium
.
It was found that the drug resistance rate of macrolides was 38% (385/1008) [5]
.
The results of a systematic review of 21 clinical studies published in Clin Infect Dis showed that the clinical cure rate of azithromycin single-dose therapy, the conventional treatment regimen, dropped from 85% reported in 1999-2008 to 67% in 2009-2013.
.
In 2013, the results of a randomized controlled trial published on Clin Infect Dis showed that the current clinical cure rate and microbiological cure rate of NGU are low, and the treatment failure of Mycoplasma genitalium is extremely common, and there is no significant difference between azithromycin and doxycycline [ 6]
.
In 2021, The New England Journal of Medicine published a randomized, double-blind, controlled clinical trial aimed at comparing the efficacy of single-dose azithromycin and doxycycline 7-day therapy in the treatment of men with male-to-male chlamydia infection.
Experiment
.
It was found that the 7-day therapy effect of doxycycline was better than that of a single dose of azithromycin
.
This article discusses the reasons for this difference in treatment course, which may be related to the following aspects: First, the minimum inhibitory concentration (MIC) of azithromycin against chlamydia in colorectal cell lines is 4 times higher than that in cervical cell lines, while doxycycline There is no difference in the MIC of chlamydia in the two cell lines
.
Secondly, doxycycline is highly fat-soluble, which is conducive to the rapid diffusion of the drug to the infected site; while azithromycin is also fat-soluble, but it is mainly transported through inflammatory cells.
If the immune response to Chlamydia rectal infection is weakened, then This may reduce the dose of azithromycin transported to the site of infection, thereby affecting the efficacy [7]
.
In the "National Guidelines for Antimicrobial Diagnosis and Treatment (Second Edition)", it is pointed out that when considering the epididymal-orchitis caused by Mycoplasma trachomatis, the first choice is not azithromycin, but ceftriaxone + doxycycline
.
Screenshot of the guidelines In 2020, there is a review of the introduction of the guidelines for the diagnosis and treatment of Mycoplasma genitalium infection in Europe, Australia, and the United Kingdom [8].
The article lists the use of azithromycin in foreign guidelines.
It has been tested for macrolide resistance sites and is not resistant.
European guidelines, the recommended first-line treatment plan is azithromycin 5-day therapy (total dose 1.
5g) or josamycin; Australian and British guidelines both recommend sequential treatment with doxycycline pretreatment, but follow-up azithromycin The course of treatment and dosage are slightly different.
The Australian guidelines recommend a 4-day course of treatment with a total dose of 2.
5g, and the British guide recommends a 3-day treatment with a total dose of 2g
.
An Australian study showed that sequential treatment with doxycycline and azithromycin can clear 94.
8% of macrolide-sensitive MG infections
.
It can be seen that none of the three guidelines recommends a single use of azithromycin
.
Screenshot of the guideline In the "Guidelines for the Diagnosis and Treatment of Syphilis, Gonorrhea, and Genital Chlamydia Trachomatis Infection (2020)", the recommended treatment for adult Chlamydia trachomatis infection is azithromycin or doxycycline, non-sequential treatment, and the total dose of azithromycin is the total dose The 2.
0g 3-day therapy is similar to the UK
.
Screenshot of the guideline Therefore, as the resistance of Mycoplasma genitalium to macrolide drugs intensifies, azithromycin is no longer the first choice for treatment, and the failure rate of azithromycin 1.
0g single dose or increased dose is still high
.
In the case of treatment failure, the bacterial load is low, so sequential or combined treatment with an antibacterial drug can be considered, with one antibacterial drug to reduce the bacterial load, while cooperating with another antibacterial drug to improve the efficacy
.
5.
Summarize and analyze the reason why the prescription dose is considered unreasonable by the pharmacist, perhaps because the cognition of azithromycin is still based on the basic cognition of "eat three stop four" and "first 500mg, maintain 250mg"
.
This also reminds us pharmacists that it is very important for our daily work to strengthen our understanding of the sensitivity of pathogenic microorganisms and to further increase our attention to clinical research
.
This time the prescription challenge, is it correct that the doctor insists on the single-dose azithromycin treatment, or is the pharmacist requesting the return of the prescription? Talk about your views in the comment section! References: [1] STD Control Center of Chinese Center for Disease Control and Prevention, STD Group of Chinese Medical Association Dermatology Branch, STD Sub-Professional Committee of Dermatologist Branch of Chinese Medical Doctor Association.
Guidelines for the diagnosis and treatment of syphilis, gonorrhea and genital tract Chlamydia trachomatis infection ( 2020)[J].
Chinese Journal of Dermatology, 2020, 053(003):168-179.
[2]Li W,Hui-Yan C.
Pediatric Clinical Pharmacology(PEOPLE'S MEDICAL PUBLISHING HOUSE Co.
, LTD, Beijing,2015 ).
[3]Zhang Dai, Liu Zhaohui.
Expert consensus on diagnosis and treatment of mycoplasma infection in the genital tract[J].
Chinese Journal of Sexuality, 2016, 025(003):80-82.
[4]Li Y, Su X, Le W, et al.
Mycoplasma genitalium in Symptomatic Male Urethritis: Macrolide Use Is Associated With Increased Resistance[J].
Clinical Infectious Diseases, 2020, 70(5):805-810.
[5]Salado-Rasmussen, Kirsten, Jensen, et al.
Mycoplasma genitalium Testing Pattern and Macrolide Resistance: A Danish Nationwide Retrospective Survey.
[J].
Clinical Infectious Diseases, 2014.
[6]Manhart LE, Gillespie CW, Sylvan LM, et al.
