Urethritis is defined as inflammation of the urethra. Although this condition may result from infectious or noninfectious etiologies, the term urethritis is typically reserved to describe urethral inflammation caused by a sexually transmitted disease (STD).[1]
Several organisms can cause infectious urethritis. This condition is normally categorized as either gonococcal urethritis (GU), due to the gram-negative intracellular diplococcus Neisseria gonorrhoeae, or nongonococcal urethritis (NGU). NGU is most commonly due to Chlamydia trachomatis, although the prevalence of Mycoplasma genitalium is on the rise.[2]
Many patients with urethritis, including approximately 25% of those with NGU, are asymptomatic and present to a clinician following partner screening.[3] Up to 75% of women with C trachomatis infection are asymptomatic.
Signs and symptoms in patients with urethritis may include the following:
See Presentation for more detail.
Urethritis can usually be diagnosed with a careful history (including social/sexual history) and physical examination. Most patients with urethritis do not appear ill or exhibit systemic signs of infection. The examination should be focused on the abdomen, pelvis, and genitalia.
Examination in male patients with urethritis includes the following:
Examine female patients in the lithotomy or frog leg position. Include the following evaluation:
Testing
Based on the current Center for Disease Control (CDC) guidelines, urethritis can be documented on the basis of any of the following signs or laboratory tests[4] :
All patients with urethritis should be tested for N gonorrhoeae and C trachomatis. Laboratory studies may include the following:
Imaging studies
Imaging studies, specifically retrograde urethrography, are unnecessary in patients with urethritis, except in cases of trauma or possible foreign body insertion.
Procedures
The following procedures may bre needed in patients with urethritis:
See Workup for more detail.
Symptoms of urethritis spontaneously resolve over time, regardless of treatment. Administer antibiotics that cover both GU and NGU. Regardless of symptoms, administer antibiotics to the following individuals:
Antibiotics used in the treatment of urethritis include the following:
See Treatment and Medication for more detail.
Urethritis is an inflammatory condition that can be infectious or posttraumatic in nature. Infectious causes of urethritis are typically sexually transmitted and categorized as either GU (ie, due to infections with Neisseria gonorrhoeae) or NGU (eg, due to infections with Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma genitalium, or Trichomonas vaginalis). The presence of Gram-negative intracellular diplococci on urethral smear is suggestive of gonococcal urethritis. Gonococcal infection is typically accompanied by chlamydial infection, which accounts for 15%-40% of NGU cases. It is essential to document chlamydial infections due to the need for partner evaluation and treatment to prevent complications from chlamydial infections, especially in female partners.
There has been a notable increase in the incidence of urethritis associated with Mycoplasma genitalium, now the second most common cause of NGU, although there is currently a lack of US Food and Drug Administration (FDA)–approved tests for diagnostic use. This organism can be sexually transmitted, accounts for 15%-25% of NGU cases in the United States and should be suspected in cases of recurrent or persistent urethritis.[2, 5]
Haemophilus species are an increasing cause of NGU, particularly in patients who have unprotected oral sex.[6, 7, 8] Rare infectious causes of urethritis include lymphogranuloma venereum, herpes simplex virus types 1 and 2, adenovirus, syphilis, mycobacterial infection, Corynebacterium,[9] and bacterial infections that are typically associated with cystitis (usually gram-negative rods) in the presence of urethral stricture. Other rare but reported causes of urethritis include viral, streptococcal, anaerobic, and meningococcal infections. However, in up to 35% of NGU cases, no pathogen is found.[10]
Posttraumatic urethritis can occur in 2%-20% of patients practicing intermittent catheterization and following instrumentation or foreign body insertion. Urethritis is 10 times more likely to occur with latex catheters than with silicone catheters.
Urethritis may be associated with other infectious conditions, such as the following:
Urethritis may be gonococcal, nongonococcal, or mixed.
Gonococcal urethritis (80% of cases) is caused by Neisseria gonorrhoeae, which is a gram-negative intracellular diplococcus. Gonococcal urethritis has a shorter incubation period than nongonococcal urethritis (NGU), and the onset of dysuria and purulent discharge is abrupt.
NGU, which comprises 50% of urethritis cases, has a longer incubation period than gonococcal urethritis, and the onset of either dysuria or, less commonly, a mucopurulent discharge, is subacute. Patients with NGU are much more likely to be asymptomatic than are patients with gonococcal urethritis.
Commonly identified causes of NGU include the following:
The number of fastidious organisms implicated in NGU is increasing and includes several Ureaplasma and Mycoplasma species. T vaginalis is another potential cause of NGU and has a reported high prevalence (20%) among heterosexual men in Africa.[11] Haemophilus species, herpes simplex virus, Epstein-Barr virus, and adenovirus can lead to urethritis in patients who practice oral to penile contact. Enteric bacteria have been implicated in patients who practice insertive anal intercourse. In most patients with NGU, the causative organism cannot be identified.
Rare cases may be related to lymphogranuloma venereum, herpes simplex, syphilis, mycobacteria, or urinary tract infection with urethral stricture. Other rare but reported causes of NGU include anaerobes, adenovirus, cytomegalovirus, and streptococcus.
Urethritis following catheterization occurs in 2-20% of patients practicing intermittent catheterization and is 10 times more likely to occur with latex catheters than with silicone catheters.
Polymicrobial NGU and cases of urethritis due to both gonococcal infection and nongonococcal factors are possible and can explain some treatment failures. This should also be considered in patients with HIV infection.
STDs are an unrecognized epidemic within the United States and pose a serious threat to the overall health and economic well-being of the population. Nearly 20 million new STDs occur each year in the US, with an estimated treatment cost of $16 billion dollars annually.[12] Urethritis occurs in 4 million Americans each year.[13]
There is currently a resurgence of various STDs that had previously been on the decline.[14] The incidence of GU steadily declined from 2000 to 2009, but then began intermittently rising. The incidence of NGU is on also the rise. The 2020 Centers for Disease Control and Prevention (CDC) STD Surveillance Report demonstrated marked increases in the incidence of syphilis and gonorrhea but a slight decrease in chlamydia, the three most commonly reported STDs. Relative to 2016, the incidence of gonorrhea increased by 45% to 677,769 cases, and syphilis incidence increased by 52% to 133,945.[15]
Although reported Chlamydia infections decreased by 1.2%, to 1.6 million cases, the CDC suggests that the decrease represents limited access to health care due to the COVID-19 pandemic rather than a reduction in new infections. The CDC points out that chlamydial infections are usually asymptomatic, so case rates are heavily influenced by screening coverage.[15]
Worldwide, approximately 62 million new cases of GU and 89 million new cases of NGU are reported each year.
Urethritis has no racial predilection. However, persons of low socioeconomic class are affected more often than persons of higher socioeconomic class.
Urethritis has no sexual predilection; however, data may be skewed because urethritis is under-recognized in women. Up to 75% of females with the condition can be asymptomatic or may instead present with cystitis, vaginitis, or cervicitis.[16] Men who have sex with men are at a greater risk for urethritis than are heterosexual males or females in general.
Urethritis may occur in any sexually active person, but incidence is highest among people aged 20-24 years.
All patients with uncomplicated urethritis spontaneously recover with or without treatment.
Complications, such as stricture, stenosis, or abscess formation, are quite rare. Concomitant epididymitis or prostatitis is not uncommon. Increasing evidence shows that genital chlamydial infection in males may predispose to infertility. In addition, both Chlamydia and U urealyticum can impair sperm and adversely affect semen parameters.[17, 18, 19]
Approximately 10%-40% of women with urethritis eventually develop pelvic inflammatory disease (PID), which may subsequently cause infertility and ectopic pregnancy secondary to postinflammatory scar formation in the fallopian tubes. PID can occur even in women with asymptomatic infections.
Children born to mothers with Chlamydia infection may develop conjunctivitis, iritis, otitis media, or pneumonia if exposed to the organism while passing through the birth canal. Performing cesarean delivery in patients with known chlamydial infections and routine treatment of all newborns with anti-chlamydial eyedrops has decreased the incidence of this problem in developed countries.
Disseminated gonococcal infection (DGI) and reactive arthritis develop in fewer than 1% of female patients with urethritis. Reactive arthritis is characterized by NGU, anterior uveitis, and arthritis and is strongly associated with the gene for HLA-B27. Rare but serious complications of DGI include arthritis, meningitis, and endocarditis.
Morbidity due to urethritis in males is less common (1%-2%), typically taking the form of urethral stricture or stenosis due to postinflammatory scar formation. Other potential complications of urethritis in males include prostatitis, acute epididymitis, abscess formation, proctitis, infertility, abnormal semen, DGI, and reactive arthritis.
Mortality rates are minimal in patients with gonococcal urethritis or NGU.
Patient should be told the following about this condition:
Educate at-risk patients on how to prevent disease recurrence and educate patients on risks of other sexually-transmitted infections, including HIV.[20] Instruct patients to avoid the following high-risk behaviors associated with STDs:
For patient education information, see the Sexual Health Center and Sexually Transmitted Diseases.
Obtaining a careful patient history often helps differentiate between a sexually transmitted disease (STD) and other causes of urethritis. The questions can be quite personal, and the physician should take care to remain objective regarding the patient's sexual history. If the patient is made to feel uncomfortable, they may not be forthcoming with essential information necessary to guide further diagnosis and treatment. This can delay or impede treatment altogether for the patient and their sexual partners, including the chain of partners that may be linked to the patient (eg, partners of partners and so on).
Certain sexual practices may increase or decrease the likelihood of contracting infectious urethritis.
Contraceptive use
Condom use substantially decreases the chance of STD transmission. Other forms of contraception either do not improve or worsen the chance of transmitting infectious urethritis. The use of spermicides may cause a chemical urethritis which can mimic the symptoms of infectious urethritis.
Age at first intercourse
Apart from certain religious groups that encourage marriage and monogamy at an early age, early age at first intercourse correlates with an increased risk of STD.
Number of sexual partners
Individuals with multiple sexual partners are more likely to contract an STD. Long-term monogamous couples are extremely unlikely to contract an STD. A married patient should not be informed of the diagnosis (or possible diagnosis) in the presence of his or her spouse, but the spouse should be treated once the patient has had the opportunity to discuss further with their spouse.
Sexual preference
Men who have sex with men have the highest rate of STDs. They are followed, in order of occurrence rates, by men who have sex with women, women who have sex with men, and women who have sex with women.
Previous STDs
Patients with a prior history of STDs are at an increased risk of contracting another STD. Concurrent STDs may also occur. A high level of suspicion for more sinister STDs, such as syphilis and HIV infection, should be maintained. In addition, urethritis can increase viral shedding of HIV and can increase the likelihood of transmission.[21]
Many patients, including approximately 25% of those with nongonococcal urethritis (NGU), are asymptomatic and present following partner screening. Up to 75% of women with Chlamydia trachomatis infection are asymptomatic.
The clinician should specifically address the following manifestations:
Systemic symptoms
Systemic symptoms (eg, fever, chills, sweats, nausea) are typically absent but, if present, may suggest disseminated gonococcemia, pyelonephritis, arthritis, conjunctivitis, proctitis, prostatitis, epididymitis or orchitis, pneumonia, otitis media, or reactive arthritis (eg, low back pain, iritis, or rash [characteristically involving the palms of hands and soles of feet]).
Most patients with urethritis do not appear ill and do not present with signs of sepsis, such as fever, tachycardia, tachypnea, or hypotension. The primary focus of the examination is on the genitalia.
It is best to avoid examination immediately following micturition as urination temporarily washes away discharge and potentially culturable organisms. Since urine culture is an important component of the evaluation, advise the patient to urinate approximately 2 hours before the examination so that culture and examination results are optimal and the patient can comfortably provide a urine specimen after the examination.
Ensure that the patient is standing, completely undressed from the waist down, and that the room is warm and with good lighting. Inspect the underwear for secretions which may yield information.
Examine the patient for skin lesions that may indicate other STDs, such as condyloma acuminatum, herpes simplex, or syphilis. The examiner must retract the foreskin of uncircumcised men to fully examine the penis and urethra.
Examine the lumen of the distal urethral meatus for lesions, stricture, or obvious urethral discharge.
Strip the urethra by gently palpating from the base of the penis to the glans to reveal any urethral discharge. Any discharge should be sampled and sent for analysis and culture. Palpate along the urethra for areas of fluctuance, tenderness, or warmth or for firmness, which may suggest abscess or foreign body, respectively.
Examine the testes for masses or inflammation. Palpate the spermatic cord, examining for swelling, tenderness, or warmth suggestive of orchitis or epididymitis.
Check for inguinal adenopathy.
Palpate the prostate for tenderness or bogginess suggestive of prostatitis. Note any lesion around the external anus during digital rectal exam.
As with male patients, it is best to avoid examination immediately following micturition. Advise the patient to urinate approximately 2 hours before the examination so that culture and examination results are optimal and the patient can comfortably provide a urine specimen after the examination.
The patient should be in the lithotomy or frog leg position.
Inspect the skin for any lesions that may indicate the presence of other STDs.
Strip the urethra by inserting a finger into the anterior vagina and gently palpating forward along the urethra. Any discharge should be sampled and sent for analysis and culture.
Follow the urethral examination with a complete pelvic examination, including cervical cultures.
Previously, urethritis was diagnosed based on Gram stain of urethral discharge demonstrating ≥ 5 white blood cells (WBC) per high power field (hpf). More recent studies suggest that utilizing a threshold of ≥ 5 WBC hpf could miss a significant proportion of infections due to Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium.[23, 24] According to the current Centers for Disease Control and Prevention (CDC) guidelines, urethritis can be documented on the basis of any of the following signs or laboratory test results[4] :
All patients with urethritis should be tested for N gonorrhoeae and C trachomatis. M. genitalium testing should be performed for men who have persistent or recurrent symptoms after initial empiric treatment. Testing for T. vaginalis should be considered in areas or among populations with high prevalence, in cases where a partner is known to be infected, or for men who have persistent or recurrent symptoms after initial empiric treatment.[4]
Traditionally, treatment was based on Gram stain results. Patients with gram-negative intracellular diplococci on urethral smear received treatment for gonococcal urethritis, and those without gram-negative intracellular diplococci received treatment for nongonococcal urethritis (NGU). Because current recommendations suggest concomitant treatment for both, and with the success of nucleic acid amplification tests (NAATs), a Gram stain may be unnecessary. Of note, the sensitivity of urethral Gram stain is highly dependent on the method of collection and the experience of the provider. A negative Gram stain does not rule out gonococcal urethritis.
Endourethral culture (obtained by gently inserting a malleable cotton-tipped swab 1-2 cm into the urethra), rather than culture of the expressible discharge, is necessary to test for C trachomatis infection. Endocervical cultures should be obtained in women.
This culture may be a useful screening tool for penicillinase-producing N gonorrhoeae or chromosomally mediated resistance to multiple antibiotics. However, the results do not influence the initial antibiotic therapy, and performing this screening may not be cost-effective. Cultures for N gonorrhoeae should be obtained in cases of sexual assault, developing antimicrobial resistance, or suspected gonorrhea treatment failures.
Urinalysis is not a useful test in patients with urethritis, except for helping exclude cystitis or pyelonephritis, which may be necessary in cases of dysuria without discharge. Patients with gonococcal urethritis may have leukocytes in a first-void urine specimen and fewer or none in a midstream specimen. More than 30% of patients with NGU do not have leukocytes in urine specimens.
Many nucleic acid–based tests for C trachomatis and N gonorrhoeae can be performed on urine specimens (see below). These require a first-voided specimen. For Chlamydia species, endourethral samples are more accurate.
Polymerase chain reaction (PCR) assays are available for gonococcal urethritis and Chlamydia infection. NAATs are also available for Mycoplasma species, Ureaplasma species, and Trichomonas vaginalis, but these are not recommended, as they are expensive and do not alter the choice of treatment.
NAATs are the preferred test for both C trachomatis and N gonorrhoeae due to their higher sensitivity and specificity. NAATs can be performed on urethral swabs or first-void urine samples. In males, first-void urine is the preferred specimen for NAATs. To prevent false-negative findings, obtain urethral swabs at least 2 hours after micturition using a calcium-alginate swab on a non-wooden stick inserted at least 1 cm in depth. If patients meet diagnostic criteria for urethritis, but Gram stain is unavailable or inconclusive, administer NAAT testing for C trachomatis and N gonorrhoeae.
DNA-based tests, unlike culture, do not allow for antibiotic susceptibility testing, but this is unnecessary in most patients as the initial antibiotic therapy will be unchanged.
The following additional tests may be considered:
Reactive arthritis is diagnosed on the basis of the presence of NGU and clinical findings of uveitis and arthritis. HLA-B27 testing is of limited value. More readily available laboratory findings, such as elevated erythrocyte sedimentation rate (ESR) in the absence of rheumatoid factor, may be helpful.
Imaging studies, specifically retrograde urethrography, are unnecessary in patients with urethritis, except in cases of trauma or possible foreign body insertion.
Procedures such as urethral catheterization and cystoscopy may be useful, especially in patients with urethral trauma.
In cases of urethral trauma, urethral catheter placement can hold the urethra open to avoid urinary retention caused by edema or a flap of elevated mucosa. The catheter also serves to tamponade urethral bleeding.
When urethral catheter placement is not possible after urethral trauma, careful negotiation of the urethra with a flexible cystoscope can allow passage of a guidewire, over which a Councill tip urethral catheter can be placed. This can generally be performed in the emergency department or outpatient clinic with local anesthesia (lidocaine jelly). However, if not easily accomplished on the initial attempt, this procedure should be aborted to avoid further urethral trauma, and a suprapubic catheter should be placed.
A foreign body or stone in the urethra, which may mimic urethritis, can be removed cystoscopically. Unless the object is very small and very distal, this procedure probably should be undertaken in the operating suite while the patient is under anesthesia. A rigid cystoscope with a larger lumen sheath and working port allows utilization of more secure endoscopic graspers. The object can often be removed through the large lumen of the cystoscope sheath, rather than pulling it through the distal urethra (which may cause further trauma).
Urethral dilation via Amplatz dilators can also be used by experienced urologists but is used less frequently in cases of urethral trauma because of the wide availability of flexible cystoscopes. In addition, this technique can lead to more severe urethral trauma if not used correctly.
With more severe urethral trauma that prevents urethral catheter placement or inadequate facilities for emergent cystoscopy in patients with urethral obstruction due to trauma or foreign bodies, a suprapubic catheter is an excellent temporizing measure to divert urine and relieve patient discomfort until definitive therapy can be undertaken.
Symptoms of urethritis typically resolve spontaneously over time, regardless of treatment. Administer antibiotics to prevent morbidity and to reduce disease transmission to others. Treating recent sexual contacts (those having sexual contact with the patient within 60 days prior to symptom onset) also prevents reinfection of the index patient.
Antibiotic therapy for urethritis should cover both gonococcal urethritis (GU) and nongonococcal urethritis (NGU). The choice of antibiotics should be based on effectiveness, adverse effects, cost, and compliance. In most situations, optimal treatment is with single-dose therapy administered in the emergency department or the physician's office.
The treatment of Neisseria gonorrhoeae has become increasingly complex due to the evolution of antimicrobial resistance and the decreased use of culture given widespread utilization of nucleic acid amplification tests (NAATs). In 2014, the Gonococcal Isolate Surveillance Project (GISP) reported that 25% of N gonorrhoeae isolates were resistant to tetracycline, 19.2% were resistant to ciprofloxacin, and 16.2% were resistant to penicillin. Reduced susceptibility to azithromycin was also noted.[14] In response to the increasing incidence of gonorrhea strains with azithromycin resistance and reduced susceptibility to ceftriaxone, the Centers for Disease Control and Prevention (CDC) revised its previous recommendation for treatment of uncomplicated gonococcal infection, eliminating azithromycin and increasing the ceftriaxone dose.
Currently, the CDC recommends a single dose of ceftriaxone 500 mg IM (1 g IM in patients weighing ≥150 kg) for the treatment of GU. If ceftriaxone is unavailable, administer cefixime 800 mg orally in a single dose. If the patient has a cephalosporin allergy or a type 1 hypersensitivity reaction to penicillins, treat with gentamicin 240 mg IM plus azithromycin, 2 g orally. If chlamydial infection has not been excluded, treatment should also include doxycycline, 100 mg orally twice a day for 7 days.[26]
Gonorrhea treatment guidelines issued by the World Health Organization (WHO) in 2016 recommend determining the choice of therapy on the basis of local antibiotic resistance data, but in settings where local resistance data are not available, the WHO recommends the same dual-therapy regimens as the CDC for treatment of genital gonorrhea.[27]
Because of widespread high levels of resistance, the WHO guidelines do not recommend fluoroquinolones for the treatment of gonorrhea. For monotherapy of genital gonorrhea, the WHO guidelines recommend a single dose of one of the following, with the choice based on recent local resistance data confirming susceptibility[27] : ceftriaxone 250 mg IM, cefixime 400 mg orally, or spectinomycin 2 g IM.
For treatment of NGU, the CDC currently recommends doxycycline, 100 mg orally twice a day for 7 days. Alternative regimens include a single dose of 1 g azithromycin orally, or 500 mg orally followed by 250 mg orally daily for 4 days.[4] The American Academy of Family Physicians recommends a single dose of ceftriaxone, 500 mg IM, plus doxycycline, 100 mg orally twice a day for seven days.[22]
The CDC no longer recommends erythromycin or levofloxacin for treatment of NGU.[4]
Patients with persistent symptoms should be reevaluated. In those with persistent or recurrent NGU, the most common organism is Mycoplasma genitalium, especially following treatment with doxycycline. Antimicrobial resistance is noted to be high for M genitalium.[28] There is a reported 31% median cure rate for doxycycline.[29]
The CDC recommends a two-stage approach for treatment for M genitalium. If M genitalium resistance testing is available it should be performed, and the results should be used to guide therapy. Treatment of macrolide-sensitive M genitalium infection is with doxycycline 100 mg orally 2 times/day for 7 days followed by azithromycin, 1 g orally initial dose then 500 mg orally daily for 3 additional days (2.5 g total).[26]
If M genitalium resistance testing is not available, the recommended treatment is doxycycline 100 mg orally 2 times/day for 7 days followed by moxifloxacin 400 mg orally once daily for 7 days. Higher doses of azithromycin have not been effective for M genitalium after azithromycin treatment failures.[4]
European guidelines for the treatment of M genitalium differ from the CDC and recommend a stepped approach[30] :
Trichomonas vaginalis infection should be considered in heterosexual patients with persistent symptoms. In regions where T vaginalis is prevalent, patients with urethritis should be treated empirically with metronidazole 2 g orally in a single dose or tinidazole 2 g orally in a single dose. The patient's partners should be referred for evaluation and treatment, if needed.[4]
See also Urethritis Empiric Therapy and Urethritis Organism-Specific Therapy.
Consider urology consultation in patients with persistent or recurrent NGU after presumptive treatment for GU, NGU, and M genitalium or T vaginalis [4] .
The most effective strategies for urethritis prevention include measures to reduce STD transmission, since the most common cause of urethritis is infectious in nature. The most reliable way to avoid STD transmission is to abstain from oral, anal, or vaginal intercourse or to remain in a long term, monogamous relationship with an uninfected partner. Male condoms, when used consistently and correctly, reduce the risk of transmission of chlamydial infection, gonorrhea, and trichomoniasis. There are few to no data regarding STD prevention with female condoms, cervical diaphragms, or topical microbicides and spermicides. Nonbarrier contraception, surgical sterilization, or hysterectomy offer no protection against STDs. In cases of noninfectious urethritis, avoid urethral irritants such as perfumed soaps, body washes, lotions, or lubricants and frequent masturbation/sexual intercourse.
Only patients who remain symptomatic require follow-up cultures to ensure eradication of infection. If symptoms persist following adequate treatment, the disease is most likely nongonococcal urethritis (NGU). Prior to improved culture methods and increased awareness of the causes of NGU, symptom recurrences were thought to be psychological in nature. This is usually not the case, and most cases of recurrent NGU are related to persistent chlamydial, ureaplasmal, or mycoplasmal infection. These patients benefit from further treatment previously mentioned.
Most infections after treatment are due to reinfection by the same or a new partner, stressing the need to educate patients and to treat partners.
Administer antibiotics to patients who meet diagnostic criteria for infectious urethritis. Treat all sexual partners of those patients, regardless of symptoms. In patients with a negative Gram stain but history concerning for urethritis, treat empirically if they are at high risk for being noncompliant with follow-up and/or are likely to continue transmitting infection (eg, commercial sex worker, intravenous drug user, homeless person). The latter group may best be served with single-dose therapies.
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.[20] Antimicrobial agents used in the treatment of gonococcal urethritis (GU) include IM ceftriaxone, oral cefixime, oral azithromycin, and IM gentamicin. Chlamydia trachomatis, the most common cause of nongonococcal urethritis (NGU), is usually treated with doxycycline; if nonadherence is a substantial concern, azithromycin is an alternative. For Mycoplasma genitalium, the second most common cause of NGU, doxycycline is also used, in combination with azithromycin or, in macrolide-resistant cases, moxifloxacin. Combinations of probenecid with penicillin, amoxicillin, or ampicillin are no longer used because of resistance.
Patients with proven GU should be empirically treated for C trachomatis infection. Empiric treatment is less expensive than culture in any population whose coinfection rate is at least 10%. Single-dose empiric treatments offer an advantage in patients who are noncompliant or unlikely to return for follow-up.