Gonorrhoea & Chlamydia (Urogenital STIs)

Meet the patient

A 19-year-old student comes to the clinic with two days of dysuria and a mucoid urethral discharge. He is embarrassed but frank: a new partner three weeks ago, no condom. His girlfriend, seen separately, has no symptoms at all — but her cervix is friable and bleeds on swabbing. The third patient in the same morning is a 24-year-old dancer with a swollen painful knee, a tender wrist, and a handful of pustules on her forearms she cannot explain.[1]

The two questions these three patients force you to answer are the two that decide every gonorrhoea and chlamydia case: whom do I treat empirically, and for both organisms? (the answer is everyone with a compatible syndrome, plus their partners of the last 60 days) and which surgical emergency am I missing? (ectopic pregnancy in the woman with pelvic pain, testicular torsion in the young man with a scrotum, septic arthritis in the dancer). Hold those two questions and every section below slots into place.[1]

Two bugs, one syndrome — why these two are taught together

Gonorrhoea and chlamydia are grouped in one topic because they share a syndrome, a test and a control logic. Both infect non-cornified columnar or transitional epithelium — urethra, endocervix, rectum, pharynx, conjunctiva. Both are usually asymptomatic (50 to 70 percent of women with chlamydia; up to half of women with gonorrhoea). Both are diagnosed by NAAT. Both demand empirical treatment for both organisms, partner tracing and a co-infection screen. And both ascend, in women, to produce pelvic inflammatory disease (PID) — the leading preventable cause of tubal-factor infertility and ectopic pregnancy worldwide.[1]

Gonorrhoea is Neisseria gonorrhoeae — a Gram-negative, oxidase-positive, catalase-positive diplococcus that grows on Thayer-Martin selective chocolate agar in 5 percent CO2, ferments glucose but not maltose (which distinguishes it from N. meningitidis), produces an IgA protease, and displays type IV pili that mediate adhesion and undergo antigenic variation — the reason no protective immunity develops and re-infection is common.[1]

Chlamydia is Chlamydia trachomatis serovars D-K — an obligate intracellular Gram-negative bacterium with a unique biphasic (elementary body to reticulate body) developmental cycle. It cannot grow on cell-free media (it needs living host cells, classically McCoy or HeLa cells), forms intracellular inclusions stained by iodine (glycogen) or fluorescein-conjugated antibody, and has an atypical cell wall that lacks peptidoglycan or muramic acid — so beta-lactam antibiotics do NOT kill the replicating reticulate body.[1]

Three facts explain the entire clinical approach:[1]

1. Most infections are silent. Fifty to seventy percent of women and up to half of men with chlamydia, and up to half of women with gonorrhoea, are asymptomatic. A clinician who waits for symptoms will miss most cases and most of the harm.
2. Silent infection causes irreversible harm in women. Ascending infection (cervix to tubes) produces pelvic inflammatory disease (PID), the leading preventable cause of tubal-factor infertility and ectopic pregnancy worldwide. Even a single treated episode of PID reduces future fertility.
3. Resistance is outpacing drugs. N. gonorrhoeae has developed resistance to every class used against it — penicillins, tetracyclines, fluoroquinolones and now declining cephalosporin susceptibility — which is why ceftriaxone remains the cornerstone and new oral agents such as zoliflodacin are being developed.[1][2][5]

Etymology for viva gold: gonorrhoea is from the Greek gonos (seed) and rheo (I flow) — Galen mistook the discharge for an involuntary flow of semen, and the name stuck. Chlamydia is from the Greek chlamys, a cloak — the intracellular inclusion cloaks itself in host-cell membrane. Both names outlived their errors because the clinical pictures are unchanged.[2][5]

C. trachomatis serovars — the classification that predicts the disease

For chlamydia, the serovar decides the disease, and every final-prof candidate is expected to reproduce the map.[1]

• Serovars A, B, Ba, C — trachoma: eye-to-eye transmission; the leading infectious cause of blindness worldwide.
• Serovars D-K — genital STI (this topic): urethritis, cervicitis, PID, neonatal conjunctivitis and pneumonia.
• Serovars L1, L2, L3 — lymphogranuloma venereum (LGV): a painless genital ulcer, inguinal buboes (the groove sign), and severe ulcerating proctitis in MSM; treated with doxycycline for 21 days, not 7.

[1]

The syndromic classification (which drives management) sorts the clinical phenotypes: urethritis, cervicitis, proctitis, pharyngitis, epididymo-orchitis, pelvic inflammatory disease, disseminated gonococcal infection, Fitz-Hugh-Curtis perihepatitis, and ophthalmia neonatorum.[1]

How common, who, and why the gonococcus keeps outwitting us

Together these are the commonest reportable bacterial infections in most high-income countries. The WHO estimates about 82 million new gonococcal infections and 128 million new chlamydial infections each year.[1]

[1]

Transmission and natural history:[1]

• Route — vaginal, anal and oral sexual contact. Oral sex is an important driver of pharyngeal gonorrhoea, a reservoir for resistant strains.
• Incubation — gonorrhoea 2 to 7 days (often 2 to 5); chlamydia 1 to 3 weeks (often 7 to 14 days). Disseminated gonococcal infection (DGI) appears about 2 to 3 weeks after mucosal acquisition.
• Communicability — an infected (often asymptomatic) person transmits with each unprotected contact; infectivity falls rapidly after effective treatment.
• Asymptomatic carriage is the dominant reservoir: women with chlamydia (50 to 70 percent), men with chlamydia (up to 50 percent), women with gonorrhoea (up to 50 percent), men with gonococcal urethritis (fewer than 10 percent).[1]

Risk factors:[1]

• Young age (under 25) — adolescent cervical ectopy (columnar epithelium exposed on the ectocervix) increases chlamydial susceptibility.
• New or multiple sexual partners; inconsistent condom use; a partner with a known STI.
• Men who have sex with men (MSM) — high rectal and pharyngeal carriage; high LGV and macrolide-resistant M. genitalium risk.
• Prior STI; commercial sex contact; substance misuse; lower socioeconomic status; residing in a high-prevalence area.[1]

Co-infection is the rule, not the exception. Ten to thirty percent of people with gonorrhoea also have chlamydia; trichomoniasis, Mycoplasma genitalium, HIV, syphilis, HSV and hepatitis B are all over-represented. A diagnosis of one STI mandates a full STI screen.[4]

The gonococcal resistance crisis is the reason the treatment regimen keeps changing. N. gonorrhoeae has acquired resistance to every class: penicillins (penicillinase-producing, PPNG), tetracyclines (tetM), fluoroquinolones (parC and gyrA mutations — now near-universal), and now declining cephalosporin susceptibility (penA mosaic plus mtrR mutations). Surveillance shows ongoing MIC creep; oral cefixime monotherapy is no longer first-line; IM ceftriaxone is the global cornerstone.[5]

The two mechanisms — pili and the intracellular cycle

The virulence of the gonococcus and the chlamydial life cycle are the two mechanisms examiners probe, because each explains a treatment decision.[1]

Neisseria gonorrhoeae — the diplococcus and its virulence. The organism is a Gram-negative diplococcus (paired, kidney-bean-shaped) found characteristically inside polymorphonuclear leucocytes on Gram stain. Its outer membrane carries lipooligosaccharide (LOS), the PorB porin, Opacity (Opa) proteins, Rmp (reduction-modifiable protein) and type IV pili.[1][5]

• Pili are the principal virulence factor: they mediate adherence to non-ciliated columnar epithelium and undergo antigenic variation (more than 10 forms via recombination at the pilE locus). This is why no protective immunity develops and re-infection is common — the immune system never quite catches the moving target.
• Opa proteins drive intimate adhesion and invasion into epithelial cells; IgA protease cleaves host secretory IgA1, subverting mucosal humoral defence.
• After attachment the gonococcus is endocytosed, replicates intracellularly, transcytoses through the epithelium into the submucosa and elicits a brisk neutrophilic inflammatory response — the purulent discharge.
• LOS activates TLR4 and cytokine release (IL-1, IL-6, TNF-alpha). The organism evades complement by binding factor H and sialylating its LOS.

[1]

Ascending infection in women runs cervix to endometrium (endometritis) to fallopian tubes (salpingitis) to tubo-ovarian abscess. Tubal mucosal destruction and scarring cause tubal-factor infertility and ectopic pregnancy. Perihepatic spread up the right paracolic gutter causes Fitz-Hugh-Curtis (perihepatitis).[3]

Disseminated gonococcal infection (DGI) occurs in 0.5 to 3 percent of untreated cases. The strains that disseminate are typically complement-resistant (bind factor H, sialylate LOS), often of the AHU or IA auxotype and PorB IA serotype. Bacteraemia seeds skin (pustules), synovium and tendon sheaths (tenosynovitis, septic arthritis) and, rarely, endocardium (aortic valve) or meninges. Complement deficiency (C5 to C9) markedly increases the risk of recurrent neisserial bacteraemia — a testable association in anyone with recurrent DGI.[5]

Chlamydia trachomatis — the obligate intracellular life cycle. C. trachomatis is an obligate intracellular Gram-negative bacterium with an atypical cell wall that lacks peptidoglycan (muramic acid) — hence beta-lactams do not kill the replicating form. It cannot be grown on cell-free media and depends entirely on a biphasic developmental cycle:[1]

• Elementary body (EB) — the infectious, extracellular, metabolically inert, small (about 300 nm), electron-dense form. It attaches to a susceptible columnar epithelial cell and enters by clathrin-mediated endocytosis.
• Inside the host cell, the EB differentiates into the reticulate body (RB) — large (about 1000 nm), metabolically active, non-infectious, which replicates by binary fission inside a membrane-bound inclusion. Crucially, the inclusion does NOT fuse with lysosomes — the key immune-evasion manoeuvre, mediated by type III secretion system effectors (Inc proteins).
• RBs re-differentiate back into EBs; the inclusion ruptures or the cell exocytoses, releasing EBs to infect neighbouring cells.

[1]

Persistence and scarring. Repeated or persistent infection drives a Th1 / IFN-γ-mediated fibrotic response; expression of chlamydial HSP60 (heat-shock protein 60) on tubal epithelium triggers delayed-type hypersensitivity and tubal scarring — the molecular basis of PID, infertility and the blinding pannus of trachoma.[3]

Host immunity is incomplete. Humoral antibodies to MOMP (major outer membrane protein) are serovar-specific, so re-infection with a different serovar is common; there is no lasting protective immunity to either organism.[1]

The clinical picture — site by site, mostly silent

The clinical picture is shaped by site of infection, sex, and whether the organism has disseminated. The single most important fact is that most infections are asymptomatic — symptomatic disease is the tip of the iceberg.[1]

Gonococcal urethritis in men (the classic symptomatic phenotype): purulent or mucopurulent urethral discharge plus dysuria, beginning 2 to 5 days after exposure. Untreated, the discharge subsides over weeks but infection persists. Gonococcal discharge tends to be frankly purulent; chlamydial is milder (clear or mucoid).[1]

Chlamydial urethritis or non-gonococcal urethritis (NGU): milder — mucoid or clear discharge, dysuria, urethral itch; 1 to 3 weeks incubation; up to half are asymptomatic. M. genitalium, Ureaplasma, Trichomonas, HSV and adenovirus are the other causes of NGU.[1]

Cervicitis in women: mucopurulent cervical discharge, cervical friability (contact bleeding on swabbing), an oedematous ectropion. Symptoms include increased or abnormal vaginal discharge, postcoital or intermenstrual bleeding, dysuria. The majority are asymptomatic. Dysuria-pyuria syndrome — dysuria with sterile pyuria in a young woman — has chlamydia as its leading cause.[1]

Proctitis (rectal infection): from receptive anal sex or, in women, perineal auto-inoculation. Anal discharge, pruritus, bleeding, tenesmus, constipation — often asymptomatic, especially gonococcal. Severe ulcerating proctitis suggests LGV (L1 to L3) rather than D-K chlamydia.[1]

Pharyngitis: usually asymptomatic; a mild sore throat. The pharynx is an important reservoir for resistant gonococci and is poorly eradicated by some regimens — always sample the pharynx in MSM and oral-sex contacts.[1]

Epididymo-orchitis (men under 35): unilateral testicular pain, swelling and tenderness, fever. Usually an STI (chlamydia or gonorrhoea). In men over 35 or in MSM, enteric organisms are more likely. Always exclude testicular torsion first (Doppler ultrasound within 6 hours).[1]

Pelvic inflammatory disease (PID): the fertility-threatening ascending complication. Lower abdominal or pelvic pain (bilateral, often dull), deep dyspareunia, abnormal bleeding (postcoital, intermenstrual), increased discharge, fever, malaise. Examination shows cervical motion tenderness, uterine and adnexal tenderness; a tubo-ovarian abscess (palpable adnexal mass, more severe systemic illness). PID may be subclinical (silent) — infertility may be the first clue to a past, unrecognised episode.[3]

Disseminated gonococcal infection (DGI) is the highest-yield exam vignette:[1]

• Arthritis-dermatitis syndrome (bacteraemic phase): migratory polyarthralgia, tenosynovitis (inflamed tendon sheaths — wrists, fingers, ankles, knees) and a pustular skin rash: typically 5 to 40 haemorrhagic pustules on the extensor surfaces of distal extremities, often over joints. The lesions are tender — a key distinction from the painless lesions of reactive arthritis.
• Septic arthritis phase: mono- or oligo-articular suppurative arthritis (knee, wrist, ankle) with effusion; synovial culture positive in this phase.
• Rarely endocarditis (aortic valve, aggressive) or meningitis — the life-threatening DGI complications.[1]

Ophthalmia neonatorum (neonatal conjunctivitis acquired at birth). The day of onset discriminates the cause:[1]

• Day 1 — chemical (silver nitrate prophylaxis; mild, self-limiting).
• Day 2 to 5 — gonococcal: hyperacute, intensely purulent, marked lid oedema and chemosis; rapid corneal ulceration and perforation → blindness if untreated. A medical emergency.
• Day 5 to 14 — chlamydial: mucopurulent, less acute; may be followed by neonatal chlamydial pneumonia at 1 to 3 months (afebrile, staccato cough, tachypnoea, diffuse infiltrates, eosinophilia, elevated IgM).
• Day 6 to 14 — HSV: vesicles, dendritic keratitis.[1]

Fitz-Hugh-Curtis syndrome (perihepatitis): right upper quadrant pleuritic pain and fever in a woman with PID; laparoscopy shows 'violin-string' perihepatic adhesions; gonococcal or chlamydial.[1]

The mimics — cervicitis versus vaginitis, and the surgical emergencies

The differential depends on the presenting syndrome. The clinical task is to distinguish gonorrhoea or chlamydia from look-alikes and not to miss a surgical emergency.[1][3]

[20] [19] [18] [16] [1]

Differential of urethral discharge in men (NGU causes). Once gonococci are excluded on Gram stain or NAAT, NGU is caused by C. trachomatis (about 40 percent), Mycoplasma genitalium (10 to 25 percent, increasingly macrolide-resistant — which changes first-line therapy), Ureaplasma, Trichomonas vaginalis (rare in MSM, common in hyperendemic regions), HSV, and adenovirus.[4]

[1]

Differential of the acute scrotum. Testicular torsion is the surgical emergency that must be excluded in ANY young male with acute testicular pain: sudden onset, high-riding, horizontal testis, absent cremasteric reflex, severe pain, nausea and vomiting; a testis is salvageable if detorsed within 6 hours. Send for urgent Doppler ultrasound and urology review; if torsion cannot be excluded, explore surgically.[1]

DGI versus reactive arthritis (Reiter syndrome) — the closest mimic of the arthritis-dermatitis syndrome:[1]

[1]

The one-line discriminator: DGI pustules are painful and few; Reiter lesions are painless. The bedside line that separates them.[1]

The bedside round — recognise the syndrome, exclude the emergency

The diagnostic task at the bedside is to (i) recognise the syndrome, (ii) exclude the surgical emergencies (torsion, ectopic), and (iii) decide whom to treat empirically while awaiting NAAT.[1]

Named signs:[1]

• Mucopurulent cervicitis — yellow or green pus at the cervical os or on the swab tip, with friability (contact bleeding). The bedside hallmark of gonococcal or chlamydial cervicitis.
• Cervical motion tenderness ("chandelier sign") — pain on moving the cervix on bimanual exam equals PID until proven otherwise.
• Strawberry cervix — petechial haemorrhages on the ectocervix — classically trichomoniasis, not gonorrhoea or chlamydia (a key distinction in a woman with discharge).
• DGI triad — migratory polyarthralgia plus tenosynovitis plus tender pustular rash on distal extremities.[1]

Examination sequence:[1]

• Urethra (men): milk the urethra from base to glans (before the patient voids) to express discharge; note colour (purulent equals gonococcal; mucoid equals chlamydial or NGU).
• Pelvic examination (speculum plus bimanual): inspect the cervix for discharge and friability; assess cervical motion, uterine and adnexal tenderness; feel for a tubo-ovarian mass. Test vaginal pH and KOH whiff to separate cervicitis from vaginitis.
• Joints and skin (suspected DGI): examine all joints and tendon sheaths for tenosynovitis; inspect the extensor surfaces of distal limbs for the characteristic few tender pustules.
• Scrotum (young male): exclude torsion — lie, cremasteric reflex, Prehn sign; arrange Doppler US within 6 hours if torsion cannot be excluded.
• Eye (neonate or adult conjunctivitis): lid eversion, fluorescein for corneal ulcer, Gram stain of exudate.[1]

History essentials — number and gender of partners, new partners in the last 3 months, condom use, sites of exposure (vaginal, anal, oral), partner symptoms, prior STI, HIV status, last menstrual period, contraception. A pregnancy test is mandatory in any woman with pelvic pain.[1]

Screen for co-infections — HIV, syphilis (RPR or VDRL plus TPHA), hepatitis B (HBsAg, anti-HBs, anti-HBc), hepatitis C (MSM or IDU), Trichomonas (women in endemic areas), M. genitalium (where tested).[1]

Confidentiality, consent and safeguarding. STI consultations are confidential. Offer partner notification. In a child or vulnerable adult, an STI mandates a safeguarding referral (consider sexual abuse); in the UK, those under 13 cannot legally consent (use Fraser competence for under-16s).[1]

The tests — NAAT first, last and always

First-line test: NAAT (nucleic acid amplification test — PCR, SDA, TMA).[1]

• Sensitivity over 90 percent and specificity over 98 percent for modern NAATs, including self-collected vaginal swabs and clinician-collected extragenital specimens.[16]
• Specimen — first-catch urine in men and women; vaginal swab in women (self-collected performs as well as clinician-collected, and vaginal specimens perform as well as cervical or urine specimens); cervical swab; urethral, rectal and pharyngeal swabs for MSM and any oral or anal exposure.[17][15]
• Sample ALL exposed sites — NAAT sensitivity is site-specific (chlamydia NAAT sensitivity is similar at endocervical, self- or clinician-collected vaginal, urethral, meatal and rectal sites but lower at the pharynx — 69 percent in MSM), so a negative urine NAAT does not exclude rectal or pharyngeal infection.[15]

Gram stain of urethral discharge (symptomatic men): intracellular Gram-negative diplococci within polymorphs — highly specific (above 95 percent) for gonorrhoea. A negative Gram stain does not exclude gonorrhoea (use NAAT). Gram stain is not valid for rectal or pharyngeal specimens (commensal Neisseria).[1]

Culture. N. gonorrhoeae grows on Thayer-Martin (chocolate agar with vancomycin, colistin, nystatin — selective for pathogenic Neisseria) in 5 percent CO2 at 35 to 37 degrees C within 24 to 48 hours; oxidase-positive, Gram-negative diplococcus; ferments glucose but not maltose (distinguishes from N. meningitidis). Culture is essential for antimicrobial susceptibility testing (the only way to track resistance), required for DGI synovial fluid, and preferred for medico-legal or sexual-assault cases. Chlamydia culture (McCoy or HeLa cells) is difficult and now rarely used except for medico-legal evidence in children.[5]

Point-of-care NAAT (e.g. GeneXpert) gives a same-day result enabling same-visit treatment, useful in outreach and high-prevalence settings.[1]

Other tests. Full blood count and CRP or ESR (raised in PID or DGI); pregnancy test (exclude ectopic); HIV, syphilis, hepatitis B and C serology (mandatory co-infection screen); urine dipstick and culture (sterile pyuria suggests chlamydia).[1]

Imaging. Transvaginal ultrasound for suspected PID — tubo-ovarian abscess, hydrosalpinx, free fluid; scrotal Doppler ultrasound to exclude torsion in epididymo-orchitis; laparoscopy (gold standard for PID but invasive) rarely needed except for severe or atypical disease or to exclude ectopic or appendicitis.[1]

Named criteria — clinical diagnosis of PID (CDC 2021). Treat empirically if no other cause is identified and ANY ONE of the minimum criteria is present:[1][3]

• cervical motion tenderness, OR
• uterine tenderness, OR
• adnexal tenderness.[1][3]

Specificity is improved by (additional criteria): oral temperature above 38.3 degrees C, abnormal mucopurulent cervical or vaginal discharge, abundant WBC on saline microscopy, elevated ESR or CRP, and laboratory confirmation of cervical N. gonorrhoeae or C. trachomatis. The most specific criteria are endometrial biopsy (endometritis), transvaginal ultrasound or MRI showing thickened fluid-filled tubes or tubo-ovarian abscess, and Doppler evidence of tubal hyperaemia.[1]

DGI-specific tests. Blood cultures (early bacteraemic phase), synovial fluid (Gram stain, culture, cell count — typically above 50,000 WBC in the septic phase), skin lesion Gram stain, culture or PCR. The highest-yield test in DGI is often NAAT of mucosal (genital, rectal, pharyngeal) sites, because disseminated lesions are frequently culture-negative.[1]

Test of cure (NAAT) is not routinely required after standard treatment, except in pregnancy, persistent symptoms, suspected re-infection, suspected treatment failure or resistance, or in high-resistance regions. If done, perform at least 4 weeks after completing therapy to avoid a false-positive from residual DNA.[1]

Resurveillance. Re-test at 3 months (re-infection rate 10 to 20 percent) regardless of whether partners were treated; in pregnancy, re-test in the third trimester.[1]

[1]

The two exclusions you must never miss, then the bundle

Most gonorrhoea and chlamydia is ambulatory. Resuscitation applies to disseminated gonococcal infection (septic arthritis, rarely endocarditis), severe PID with tubo-ovarian abscess or sepsis, and gonococcal ophthalmia (a sight-threatening emergency).[1]

ABCDE. Airway patent; give oxygen if septic or hypoxic. Circulation — IV access; resuscitate septic shock with IV fluids and vasopressors per sepsis guidelines, with urgent antibiotics and source control; escalate to critical care early.[1]

Septic arthritis (DGI phase 2): urgent joint aspiration (Gram stain, cell count, culture) before antibiotics if possible — but do not delay antibiotics; admit for IV ceftriaxone; orthopaedic washout if the joint is frankly septic or not responding.[1]

Tubo-ovarian abscess: IV antibiotics (PID regimen), analgesia, IV fluids; monitor for rupture (peritonitis, septic shock); surgical or radiological drainage if the abscess is large, there is persistent fever, or rupture; gynaecology involvement.[1]

Gonococcal ophthalmia (any age): urgent ophthalmology review, saline irrigation, IV or IM ceftriaxone, topical antibiotics; fluorescein examination for corneal ulcer. This is sight-threatening.[1]

Two exclusions you must NEVER miss before treating empirically:[1]

1. Ectopic pregnancy in any woman with pelvic pain — serum beta-hCG plus transvaginal US before attributing the pain to PID.
2. Testicular torsion in any young male with an acute scrotum — Doppler ultrasound within 6 hours; explore if torsion cannot be excluded.[1]

Definitive treatment — six principles, then the regimens

Six general principles apply to every case:[1]

1. Treat empirically AND for BOTH organisms (gonorrhoea plus chlamydia) — co-infection is too common to gamble on.
2. Trace and treat partners of the last 60 days; consider expedited partner therapy (EPT).
3. Screen for co-infections — HIV, syphilis, hepatitis B and C, Trichomonas, M. genitalium.
4. Advise sexual abstinence for 7 days after single-dose therapy (or until a 7-day course is completed) AND until partners are treated.
5. Re-test at 3 months (re-infection), not as a test of cure.
6. Test of cure only in pregnancy, persistent symptoms, suspected resistance, or high-resistance regions.[1]

Uncomplicated gonorrhoea (urethra, cervix, rectum, pharynx)

First-line: ceftriaxone 500 mg IM as a single dose — the 2021 CDC STI Treatment Guidelines increased the ceftriaxone dose to 500 mg (1 g if body weight is over 150 kg) — PLUS doxycycline 100 mg PO twice daily for 7 days to cover co-existent chlamydia. This replaced the historical ceftriaxone plus azithromycin dual therapy (still the standard-of-care comparator in recent phase 3 trials: ceftriaxone 500 mg IM plus azithromycin 1 g orally) — driven by macrolide-resistance concerns in M. genitalium and emerging azithromycin resistance in N. gonorrhoeae itself.[8][9][2][4][5]

If cephalosporin allergy or not available: gentamicin 240 mg IM plus azithromycin 2 g orally, OR gemifloxacin 320 mg orally plus azithromycin 2 g orally — both proved effective non-cephalosporin backup combinations in a randomised multisite trial (microbiological cure 100 percent and 99.5 percent). Avoid fluoroquinolones as first-line (widespread resistance); use only if the strain is known susceptible.[10][5]

Uncomplicated chlamydia (D-K; urethra, cervix, rectum)

First-line: doxycycline 100 mg PO twice daily for 7 days — superior cure to single-dose azithromycin, especially for rectal infection (anorectal cure 94 versus 85 percent in the CHLAZIDOXY randomised trial; Cochrane finds a higher microbiological failure rate with azithromycin single dose in men, RR 2.45). Alternative: azithromycin 1 g PO as a single dose — the standard where doxycycline is unsuitable (including pregnancy) or a 7-day course is unlikely to be completed; azithromycin has fewer adverse events than doxycycline.[6][7][12]

In pregnancy

• Chlamydia: azithromycin 1 g as a single dose — Cochrane finds azithromycin and erythromycin similarly efficacious in pregnancy (RR 1.11); erythromycin and clindamycin are alternatives.
• Gonorrhoea: ceftriaxone 500 mg IM single dose — the same first-line regimen as in non-pregnant adults.
• Antenatal screening matters because untreated maternal infection risks neonatal chlamydial pneumonia or gonococcal or chlamydial ophthalmia in the newborn.

[2] [12] [14]

Pelvic inflammatory disease

Outpatient (mild to moderate, no TOA, not pregnant, tolerates oral): a single IM dose of ceftriaxone plus doxycycline for 14 days plus metronidazole for 14 days. The randomised-trial evidence behind this backbone: adding 14 days of metronidazole to single-dose ceftriaxone plus 14 days of doxycycline reduced endometrial anaerobes (8 versus 21 percent), cervical M. genitalium (4 versus 14 percent) and residual pelvic tenderness (9 versus 20 percent). Review at 48 to 72 hours; admit if no improvement.[11][3]

Inpatient (severe illness, pregnancy, tubo-ovarian abscess, failed outpatient therapy, surgical abdomen not excluded, non-adherence): parenteral ceftriaxone plus doxycycline plus metronidazole, switching to oral doxycycline plus metronidazole to complete 14 days when improving. A large or ruptured tubo-ovarian abscess needs surgical or radiological drainage.[11][3]

Epididymo-orchitis (men under 35)

Ceftriaxone plus doxycycline where gonorrhoea is a realistic cause — BASHH recommends this combination in those at high risk of gonorrhoea — and doxycycline or ofloxacin where gonorrhoea is considered unlikely (negative microscopy for Gram-negative intracellular diplococci and no gonorrhoea risk factors). ALWAYS exclude testicular torsion first.[21]

Disseminated gonococcal infection

• Arthritis-dermatitis syndrome: admit for parenteral ceftriaxone — published disseminated gonococcal disease series report complete recovery after 7 days of ceftriaxone therapy.
• Septic arthritis: urgent joint aspiration (Gram stain, cell count, culture) before antibiotics where possible — but do not delay antibiotics; parenteral ceftriaxone with a longer course than arthritis-dermatitis alone; orthopaedic washout or drainage if the joint is frankly septic.
• Endocarditis or meningitis (rare, life-threatening): prolonged parenteral therapy with cardiology or neurology input; valve replacement if needed.

[24] [1]

Ophthalmia neonatorum and neonatal chlamydia

• Gonococcal ophthalmia: a single dose of ceftriaxone — the established treatment of choice for gonococcal ophthalmia neonatorum — plus frequent saline irrigation; urgent ophthalmology review, admission and isolation; this is sight-threatening. Treat the mother and her partner.
• Chlamydial conjunctivitis or pneumonia: systemic oral therapy is required — topical prophylaxis has no efficacy against chlamydial ophthalmia, so ointment alone is inadequate. Treat mother and partner.
• Prophylaxis at birth — topical erythromycin 0.5 percent ophthalmic ointment (mandated by law in many US states) targets gonococcal ophthalmia but does not prevent chlamydial ophthalmia.

[22] [23]

Partner management and public health

• Partner notification: trace partners of the last 60 days; treat them empirically (or by their NAAT result).
• Expedited partner therapy (EPT): where legal, give the index patient a prescription or medication to deliver to the partner without the partner being clinically evaluated — CDC-recommended; reduces re-infection.
• Abstinence: until 7 days after single-dose therapy (or completion of a 7-day course) AND until partners are treated.
• Re-test at 3 months for re-infection (10 to 20 percent).
• Notification: gonorrhoea and chlamydia are notifiable diseases in most jurisdictions.

[1]

New and emerging agents

Zoliflodacin — an oral spiropyrimidinetrione that inhibits bacterial DNA gyrase B by a distinct mechanism — was non-inferior to ceftriaxone plus azithromycin for uncomplicated urogenital gonorrhoea in a phase 3 international trial (Luckey 2026, Lancet), developed through a WHO or GARDP partnership with GSK. It is positioned as a future oral option for cephalosporin-resistant gonorrhoea. Gepotidacin — a triazaacenaphthylene that inhibits DNA gyrase and topoisomerase IV by a novel mechanism — is another agent in late-stage trials.[2]

Drugs NOT to use

• Penicillins (resistance — PPNG), fluoroquinolones (near-universal resistance; contra-indicated in pregnancy and children), macrolides as monotherapy for gonorrhoea (inadequate, drives resistance).
• Tetracyclines in pregnancy and children under 8 (teratogenic, tooth discolouration).
• Topical therapy alone for chlamydial neonatal disease (fails to eradicate nasopharyngeal carriage).

[1]

How patients come to harm — the preventable list

In women: PID (in 10 to 20 percent of untreated chlamydia, similar for gonorrhoea), tubal-factor infertility (about 12 percent after one PID episode, over 50 percent after three), ectopic pregnancy (6 to 10 fold increased), chronic pelvic pain (up to 30 percent after PID), tubo-ovarian abscess, Fitz-Hugh-Curtis perihepatitis.[3]

In men: epididymo-orchitis (rarely infertility — usually unilateral), urethral stricture (historical; rare now), prostatitis (rare).[1]

In pregnancy and the neonate: preterm labour, premature rupture of membranes, postpartum endometritis, neonatal conjunctivitis (ophthalmia neonatorum) and neonatal pneumonia; maternal gonorrhoea is associated with miscarriage and neonatal sepsis.[1]

Disseminated gonococcal infection: septic arthritis (joint destruction if untreated), tenosynovitis, pustular dermatitis; rarely gonococcal endocarditis (aortic valve, aggressive) and meningitis — the life-threatening DGI complications.[1]

Increased HIV transmission: genital gonorrhoea or chlamydia increases HIV acquisition and transmission 2 to 5 fold (mucosal inflammation recruits HIV target cells); treating STIs reduces HIV incidence.[1]

Reiter syndrome (reactive arthritis) after chlamydia: asymmetric oligoarthritis, conjunctivitis, urethritis, HLA-B27; painless keratoderma blennorrhagicum; distinguish from DGI.[1]

Classic pitfalls (the examiner's favourites):[1][3]

1. Treating the index patient and missing the partner (re-infection) — always partner notification or EPT.
2. Treating only the symptomatic site — missing rectal or pharyngeal infection (sample all exposed sites).
3. Using azithromycin for gonorrhoea (inadequate, drives resistance).
4. Using doxycycline in pregnancy (teratogenic).
5. Not screening for co-infections (HIV, syphilis, hepatitis).
6. Missing DGI by attributing the rash or arthritis to reactive or rheumatological disease.
7. Missing testicular torsion in "epididymo-orchitis".
8. Missing ectopic pregnancy in "PID".
9. Not re-testing at 3 months (re-infection).
10. Using a NAAT test of cure too early (false positive from residual DNA).
11. Not considering LGV (L1 to L3) in severe proctitis.
12. Missing the safeguarding issue of an STI in a child.[1][3]

Prognosis, disposition and follow-up

• Uncomplicated gonorrhoea or chlamydia: cure rates above 95 to 99 percent with the correct regimen and adherence; no long-term sequelae if treated before ascending or dissemination.
• PID: even with correct treatment, fertility is reduced — cumulative infertility about 12 percent after one episode, 25 percent after two, over 50 percent after three; ectopic pregnancy risk 6 to 10 fold; chronic pelvic pain in up to 30 percent. Hence the imperative for early empirical treatment.
• DGI arthritis-dermatitis: complete recovery with IV ceftriaxone; septic arthritis may leave residual joint damage if treatment is delayed; endocarditis or meningitis carry serious mortality.
• Ophthalmia neonatorum: gonococcal — blindness if untreated within 24 to 48 hours; chlamydial usually resolves but may scar the cornea.

[1]

Disposition. Outpatient for uncomplicated urethritis, cervicitis, proctitis, pharyngitis and mild PID. Admit for severe PID or TOA, pregnancy with PID, DGI with septic arthritis, endocarditis or meningitis, gonococcal ophthalmia (any age), failed outpatient therapy, non-adherence, an unexcluded surgical abdomen, or safeguarding concerns.[1]

Follow-up: clinical review at 48 to 72 hours for PID (admit if worse); test of cure (NAAT at 4 weeks) in pregnancy or persistent symptoms; re-test (NAAT) at 3 months for re-infection.[1]

Special populations — pregnancy, neonates, MSM, complement deficiency

• Pregnancy: screen at the first antenatal visit — the USPSTF recommends screening all sexually active women 24 years or younger, and older women at increased risk, for chlamydia and gonorrhoea, including during pregnancy; treat chlamydia with azithromycin 1 g (not doxycycline; azithromycin has efficacy similar to erythromycin in pregnancy) and gonorrhoea with ceftriaxone 500 mg IM — treating maternal infection prevents neonatal chlamydial pneumonia and gonococcal or chlamydial ophthalmia.[14][12][9]
• Neonates: prophylaxis at birth with topical erythromycin 0.5 percent ophthalmic ointment (mandated by law in many US states) targets gonococcal but not chlamydial ophthalmia; gonococcal ophthalmia is treated with a single dose of ceftriaxone plus irrigation.[23][22]
• Children (non-neonatal) with an STI: mandatory safeguarding or child-protection referral — consider sexual abuse; culture (not NAAT alone) may be needed for medico-legal evidence.
• MSM: screen at ALL exposed sites (urethral or urine, rectal, pharyngeal) — chlamydia NAAT sensitivity is high at urethral (99 percent), meatal (100 percent) and rectal (92 percent) sites but lower at the pharynx (69 percent); rising antimicrobial-resistant gonorrhoea; high LGV risk in severe proctitis; consider HIV PrEP.[15]
• HIV-positive: no change to the gonorrhoea or chlamydia regimen, but screen for all co-infections and recognise that STIs increase HIV transmission; anogenital LGV is more aggressive.
• Elderly: STIs are increasingly recognised; atypical discharge attributed to UTI or atrophic vaginitis — consider an STI in any sexually active older adult.
• Terminal complement deficiency (C5 to C9): markedly increased risk of disseminated neisserial infection — screen for complement deficiency in anyone with recurrent DGI.
• Sexual assault or rape: full STI screen at presentation with scheduled repeat testing, HIV and hepatitis B post-exposure prophylaxis, emergency contraception, forensic specimens (chain of custody), psychological support, and reporting per jurisdiction.

[1]

Evidence, guidelines and regional differences

• CDC 2021 STI Treatment Guidelines (Workowski, MMWR Recomm Rep 2021) — the current international standard for treatment of gonorrhoea, chlamydia, PID, epididymo-orchitis and DGI; shifted gonorrhoea therapy from dual ceftriaxone plus azithromycin to ceftriaxone monotherapy at a higher dose (500 mg; 1 g if over 150 kg) to slow macrolide resistance in M. genitalium.[1][8]
• Luckey et al. (Lancet 2026) — phase 3 non-inferiority trial of oral zoliflodacin versus ceftriaxone plus azithromycin for uncomplicated urogenital gonorrhoea; the first new-in-class oral agent for resistant gonorrhoea, developed through the WHO or GARDP partnership with GSK.[2]
• Brunham et al. (NEJM 2015) — the definitive modern review of pelvic inflammatory disease: pathogenesis, clinical approach, treatment, and the long-term consequences (infertility, ectopic, chronic pain) that justify early empirical PID treatment.[3]
• Machalek et al. (Lancet Infect Dis 2020) — prevalence of macrolide and fluoroquinolone resistance mutations in M. genitalium; the rationale for shifting azithromycin away from empiric NGU cover.[4]
• Golparian et al. (Lancet Microbe 2024) — antimicrobial-resistant N. gonorrhoeae in Europe 2020 versus prior years; the surveillance basis for treatment recommendations and the resistance crisis driving the ceftriaxone-dose increase.[5]
• Peuchant et al. (Lancet Infect Dis 2022) — randomised trial of doxycycline versus azithromycin for anorectal chlamydia; doxycycline is superior, especially for rectal infection; the basis for doxycycline as preferred first-line chlamydia therapy.[6]
• Paez-Canro et al. (Cochrane Database Syst Rev 2019) — Cochrane review of antibiotics for urogenital chlamydia; doxycycline and azithromycin both highly effective; doxycycline microbiologically superior.[7]

Regional deltas:[1][5]

Controversies. Gonorrhoea monotherapy versus dual therapy — the CDC 2021 guidelines raised ceftriaxone monotherapy to 500 mg (1 g if over 150 kg); USPSTF screening of women 24 or younger has moderate net benefit but the evidence in men is insufficient; doxycycline post-exposure prophylaxis (doxy-PEP) reduced incident bacterial STIs by 56 percent in pooled randomised-trial analysis (overall RR 0.44) among MSM and transgender women — chlamydia RR 0.19, syphilis RR 0.23, gonorrhoea RR 0.55 — with ongoing concern about antimicrobial resistance.[8][14][13]

The mantra, and the mnemonics

[5] [1]

The mantra: treat for both bugs and both partners, sample every exposed site, exclude torsion and ectopic before you write PID, and re-test at three months.[1]

Ward-round test — three stems, thirty seconds each

Stem 1 — the man from the top of the topic (answer)

The 19-year-old with dysuria and a mucoid urethral discharge, three weeks after an unprotected new partner. What is the first investigation and the first treatment? Model: This is urethritis until proven otherwise — most likely gonorrhoea or chlamydia. Take a first-catch urine NAAT for N. gonorrhoeae and C. trachomatis (and, if MSM, rectal and pharyngeal swabs). Treat empirically for both organisms: ceftriaxone 500 mg IM single dose plus doxycycline 100 mg twice daily for 7 days. Trace and treat partners of the last 60 days (consider EPT), screen for HIV, syphilis and hepatitis, advise abstinence for 7 days, and re-test at 3 months for re-infection. Do NOT use azithromycin for gonorrhoea monotherapy — it drives resistance.[9][6][1]

Stem 2 — the dancer with the pustules (answer)

A 24-year-old dancer presents with a swollen painful knee, a tender wrist, and a handful of painful haemorrhagic pustules on her forearms. She has had a new partner recently. What is this, and what do you do? Model: This is disseminated gonococcal infection (DGI) — the arthritis-dermatitis syndrome: the triad of migratory polyarthralgia, tenosynovitis and arthritis with skin lesions. Take NAAT at genital, rectal and pharyngeal sites (highest-yield, because disseminated lesions are often culture-negative), plus blood cultures and synovial fluid (Gram stain, cell count, culture). Treat with parenteral ceftriaxone for about 7 days (complete recovery is reported in published series; use longer courses for septic arthritis, endocarditis or meningitis), with joint washout if frankly septic. Screen for co-infections and test for complement deficiency (C5 to C9) if she has recurrent DGI. The discriminator from reactive arthritis: DGI pustules are painful; Reiter lesions are painless.[24][1]

Stem 3 — the day-3 neonate with purulent eyes (answer)

A three-day-old neonate has hyperacute, intensely purulent bilateral conjunctivitis with marked lid oedema; the mother had no antenatal care. What is this, and what is the emergency management? Model: This is gonococcal ophthalmia neonatorum — hyperacute, intensely purulent conjunctivitis with marked lid oedema in the first days of life, and sight-threatening (rapid corneal ulceration and perforation). Manage as an emergency: urgent ophthalmology review, frequent saline irrigation, and a single dose of ceftriaxone — the established treatment of choice — plus fluorescein examination for corneal ulcer, admission and isolation. Treat the mother and her partner. Distinguish from chlamydial conjunctivitis (later onset, mucopurulent — it needs systemic therapy because topical prophylaxis does not prevent chlamydial ophthalmia). Earlier onset favours gonococcal; later onset favours chlamydial or HSV disease.[22][23]

References

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