A formidable foe who needs new treatment, diagnostic options
November 19, 2021
4 minutes to read
Source / Disclosures
Disclosures: Brock does not report any relevant financial disclosure.
As a pharmacist specializing in infectious diseases who works in a hospital setting, I do not often meet patients with Genital mycoplasma.
However, I was recently asked about obtaining defamulin for an outpatient with persistent Mr. genital infection despite some standard treatment courses.
Mr. genital has been an established cause of sexually transmitted infections in both men and women since it was first identified in the early 1980s. The true incidence of Mr. genital in the United States is not really known because it is not a reportable infection, and few epidemiological studies have been performed in the general population. However, a recent meta-analysis reported a global prevalence of 1.3% to 3.9%, with countries with the lowest levels of development having the highest rates. The incidence in high-risk groups such as patients screened at sexual health clinics has reached 35%, especially in men with nongonococcal urethritis.
Mr. genital is primarily associated with non-gonococcal and non-chlamydial urethritis in men and cervicitis in women. More serious complications such as pelvic inflammatory disease, spontaneous abortions and infertility have also been associated with Mr. genital infections in women. It is a fastidious, very slowly growing organism that complicates both diagnostic techniques and obtaining information on susceptibility. Because Mr. genital cultures can take up to 6 months, culture-free diagnostics such as nucleic acid amplification tests are the primary diagnostic mechanism. Unfortunately, molecular tests to detect markers of antimicrobial resistance are not commercially available in the United States at this time. The lack of resistance testing available, as well as the limited number of antibiotics available for management Mr. genital infections, creates a significant problem when trying to treat patients with this infection, especially those with recurrent or persistent infection.
Antibiotic resistance is a growing problem for STIs, and Mr. genital is no exception. The prevalence of macrolide resistance with Mr. genital is high and continues to increase in many parts of the world, with most countries reporting more than 40% resistance. Treatment with azithromycin alone may select for resistance during treatment of strains sensitive to macrolides and is not recommended. This is why two-step therapy is recommended in the CDC’s new STI treatment guideline (table). Starting doxycycline treatment reduces the burden on the body, facilitates clearance and may help reduce the risk of developing resistance. A recent study recruited men with symptoms of urethritis from six STD clinics and found that among those treated with azithromycin-only therapy, persistent symptoms were reported by 25.8% of patients. with macrolide resistant disease. Mr. genital infection, while 13% of people without macrolide resistance reported persistent symptoms.
Resistance to fluoroquinolones has also arisen due to mutations in the regions determining resistance to quinolones of the throughgene C. The prevalence of this mutation in the United States has been reported to be 15%. This resistance is of clinical importance because studies have shown a significant decrease in clinical cure rates after treatment with moxifloxacin from 100% before 2010 to 89% in subsequent studies.
Lefamulin is a pleuromutilin that inhibits bacterial protein synthesis by binding to the 50S subunit at the center of peptidyl transferase, which prevents the formation of peptide bonds. It has a novel mechanism of action through a unique adjustment mechanism induced to close the binding pocket in the ribosome, which ensures tight binding of the drug to the target site. Due to this mechanism, cross resistance with other classes of antibiotics is low. It has potent in vitro activity against many gram-negative and gram-positive bacteria.
Although published clinical studies are lacking, in vitro data suggest that lefamulin has potent activity against pathogens that commonly cause STIs, including multidrug-resistant drugs. Neisseria gonorrhoeae and Mr. genital. Lefamulin penetrates genitourinary tissues, including the prostate and pelvic tissues, making it an attractive agent for the treatment of STIs, particularly in populations with high levels of resistance to macrolides or fluoroquinolones, and in those for whom treatment with standard antibiotic regimens has failed.
Lefamulin is available in IV and oral formulations. Unfortunately, the cost of lefamulin can certainly be a drag, in addition to obtaining insurance clearance, which can be difficult. The oral dosage of defamulin is 600 mg twice a day, with a current average wholesale cost of around $ 330 per day of treatment. A patient assistance program is available, along with other patient access resources that may be helpful in obtaining the agent for patients.
Solithromycin is another promising agent that is not approved by the FDA but has potent activity against Mr. genital. However, solithromycin was found to be inferior to ceftriaxone in combination with azithromycin for the treatment of uncomplicated genital gonorrhea in the SOLITAIRE-U trial.
Emerging resistance and limited treatment options for resistant or relapsing people Mr. genital infections present significant challenges in the management of these infections. When faced with symptomatic treatment failure or a positive cure test after standard treatment regimens, CDC guidelines recommend consulting with experts to help guide treatment options. Clearly, new treatment options are needed. Most importantly, improved diagnostic tests are needed to quickly identify those infected with Mr. genital while simultaneously identifying antimicrobial resistance so that treatments can be optimized to improve patient outcomes. Continue to process Mr. genital infections without knowing the resistance profile can actually worsen our resistance problems with that infection by increasing treatment failures and increasing the risk of transmission to others.
- The references:
- Bachmann LH, et al. Clin Infect Dis. 2020; doi: 10.1093 / cid / ciaa293.
- Baumann L, et al. Sex Transm Infect. 2018; doi: 10.1136 / sextrans-2017-053384.
- Bradshaw C, et al. J Infect Dis. 2017; doi: 10.1093 / infdis / jix132.
- Chen MY, et al. Lancet Infect Dis. 2019; doi: 10.1016 / S1473-3099 (19) 30116-1.
- Gnanadurai R, Fifer H. Microbiology. 2020; doi: 10.1099 / mic.0.000830.
- Li, Y et al. Int J MST AIDS. 2017; doi: 10.1177 / 0956462416688562.
- Paukner S, et al. Chemother Antimicrobial Agents. 2018; doi: 10.1128 / AAC.02380-17.
- Veve M, Wagner JL. Pharmacotherapy. 2018; doi: 10.1002 / phar.2166.
- Workowski KA, et al. Recommended Representative MMWR 2021; doi: 10.15585 / mmwr.rr7004a1.
- For more information:
- Jeff Brock, PharmD, MBA, BCPS AQ-ID, is a Infectious Disease News Editorial board member and infectious disease pharmacy specialist at Mercy Medical Center in Des Moines, Iowa. He can be contacted at: [email protected]