There has been a steady increase in syphilis, gonorrhea, and chlamydia infections in men who have sex with men (MSM).¹ It is important to test patients to ascertain their sexually transmitted infection (STI) status prior to treatment. In addition, there are a number of guidelines that discuss treatment strategies for STIs such as the WHO,² CDC,³ and IUSTI.⁴

There are no new recommendations for the treatment of primary, secondary, early latent, late latent, neurosyphilis, ocular and auricular syphilis. The treatment options for syphilis are listed in Table 1.⁵

After proper treatment, the VDRL ratios should steadily decrease over time.

There are some problems with syphilis treatment in regards to availability of medications. Penicillin G procaine has had problematic availability for congenital syphilis and as an alternative treatment for both neurosyphilis and ocular syphilis.

Alternative for congenital syphilis:

• aqueous crystalline penicillin G (100,000-150,000 units/kg/day) can be administered as 50,000 units/kg/dose IV every 12 hours for the first 7 days of life and every 8 hours thereafter for a total of 10 days;
• benzathine penicillin G 50,000 units/kg/dose IM in a single dose is another option.

Alternative for neurosyphilis:

• aqueous crystalline penicillin G (18-24 million units per day) administered as 3-4 millions units IV every 4 hours or continuous infusion, for 10-14 days.

Gonorrhea is the second most common bacterial STI. The biggest issue with gonorrhea infections is the growing antibiotic resistance. Antibiotic resistance usually emerges in the western pacific region and then spreads to other parts of the world. Penicillin resistance was noted in the 1970s, followed by spectinomycin in the 1980s, fluoroquinolones in the 1990s, and extended-spectrum cephalosporins (ESCs) in the 2000s. Gonorrheal strains have decreased susceptibility to cefixime and verified treatment failures were observed.^6,7 Resistance to cefixime has more than doubled in Austria with 0.7% resistance to 11.9% from 2015 to 2016.⁶ Ciprofloxacin has a >50% resistance rate and thus is not recommended in the guidelines for treatment.⁸

To date, the susceptibility to ceftriaxone is decreasing globally.⁹ There have been confirmed treatment failures of pharyngeal gonorrhea in Sweden, Slovenia, France, Spain, and Australia.¹⁰

Extended-spectrum cephalosporin (ESC) gonococcal resistance is due to the acquistion of a penA mosaic allele.¹¹ This leads to an alteration of the amino acid (A501) and subsequent protein (penicillin-binding protein 2 or PBP2). Mutations in the promoter and/or coding sequence affect the repressor gene mtrR.

MSM are linked to a higher emergence and spread of antimicrobial resistant gonococci including tetracycline, fluoroquinolones, and ESCs.¹²

Azithromycin resistance is also increasing in different populations with all males, MSM, and males who have sex with women (MSW) having the highest rates of resistance.¹³

Dual first-line therapy for gonorrhea varies slightly by country (Table 2).¹⁴

However, a combined resistance has been identified with this treatment begging the need for additional effective therapies.¹⁵

Alternatives to treatments include:

• gentamycin;
• ertapenem and tigecycline;
• fosfomycin;
• zoliflodacin;
• gepotidacin.

The treatment options for Chlamydia are listed in Table 3.⁵

There is conflicting evidence in the literature regarding the efficacy of doxycycline versus azithromycin with a United States study showing significance and a European study showing minimal difference.^16,17 A study by Hathorn et al demonstrated a 26% treatment failure with azithromycin compared to 0% with doxycycline.¹⁸ A metanalysis of randomized controlled trials comparing azithromycin 1 g versus doxycycline 100 mg twice a day for 7 days showed a 97.9% cure rate for doxycycline and 96.5% for azithromycine.¹⁹

In rectal chlamydia, use of doxycycline 100 mg twice a day for 7 days or azithromycin 1 g was associated with 8% and 22% persistent/recurrent infections, respectively.²⁰ Therefore, doxycycline may be more effective than azithromycin in the treatment of rectal chlamydial infections.

Mycoplasma genitalium (M. genitalium) plays an important role in non-chlamydial, non-gonococcal urethritis (NCNGU). It may cause a number of issues in men [non-gonococcal urethritis (NGU), postgonococcal urethritis (PGU), prostatitis, balanoposthitis] and is more prevalent in MSM.²¹ It also has a presence in women and is known to cause cervicitis, pelvic inflammatory disease (PID), infertility, and preterm delivery.^22,23 Recommended treatment are listed in Table 4.⁵

Some common problems associated with M. genitalium is the lack of beta lactam activity as the mycoplasma has no cell walls. Tetracyclines have a poor microbiologic cure rate (30%) with temporary clinical improvement. Macrolides and fluoroquinolones are prone to resistance.

New antimicrobials are in the pipeline but need documentation.