Dysuria in pregnancy

Dysuria in pregnancy is pain, burning or discomfort on passing urine. It is most often caused by cystitis, but it can come from urethritis, vulvovaginal infection, genital herpes, vulval skin disease, stones, or an upper tract infection.

The main clinical points are to send a urine culture before treatment in every pregnant woman with urinary symptoms, to look for upper tract infection and sepsis, to treat bacteriuria even without symptoms because of the high risk of progression to pyelonephritis, to choose antibiotics that are safe for the foetus, and to check for sexually transmitted infection.

Clinical relevance. Urinary tract infection is the commonest bacterial infection in pregnancy. Untreated bacteriuria progresses to pyelonephritis in about a quarter of women, and pyelonephritis is a leading non obstetric cause of admission and sepsis in pregnancy. Urinary infection is linked to preterm labour, low birthweight and, with group B streptococcus, neonatal sepsis.

Physiology. Progesterone relaxes the ureters and bladder, the renal pelvis and ureters dilate (more on the right) from the first trimester onwards, the bladder is displaced and the residual volume rises. Glycosuria is common from raised filtration, and urine becomes more favourable for bacterial growth. Urinary frequency, urgency and nocturia are normal in pregnancy and are not dysuria.

Mechanisms. Bacteria from the perineum ascend the urethra into the bladder and, with urinary stasis, into the kidneys. Escherichia coli causes about 80% of infections; others include Klebsiella, Proteus, Enterobacter, Enterococcus, Staphylococcus saprophyticus and group B streptococcus. Dysuria without bacteriuria arises from urethral and vulval inflammation (sexually transmitted infection, candidiasis, atrophic or chemical irritation) or from stones.

Classification. Asymptomatic bacteriuria: a significant growth on culture without symptoms. Acute cystitis: dysuria, frequency, urgency, suprapubic pain, with or without haematuria. Acute pyelonephritis: cystitis with fever, loin pain and tenderness, rigors, nausea and vomiting. Recurrent infection: two or more episodes in pregnancy. Urethritis and vaginitis: dysuria with discharge. Sterile pyuria and dysuria: chlamydia, tuberculosis, stones.

Key distinctions. Internal dysuria (pain inside) favours urethral or bladder disease; external dysuria (pain as urine touches the vulva) favours vulvovaginitis or herpes. Dysuria with vaginal discharge points to genital infection rather than cystitis. Fever, loin pain and vomiting indicate upper tract disease. Haematuria with colic suggests a stone.

History

• Symptoms: onset, duration, internal or external burning, frequency, urgency, nocturia change, haematuria, cloudy or foul urine, suprapubic pain, loin pain, fever, rigors, nausea, vomiting, hesitancy or retention, incontinence.
• Gynaecological: vaginal discharge, itch, soreness, genital ulcers or blisters, new sexual partner, unprotected intercourse, contact with infection, previous sexually transmitted infection.
• Obstetric: gestation, contractions, bleeding, leaking fluid, foetal movements, previous preterm birth, previous urinary infection in pregnancy.
• Medical: diabetes, sickle cell trait or disease, renal disease, renal transplant, stones, congenital urinary tract anomaly, neurological disease or catheter, immunosuppression, HIV.
• Drugs: antibiotics taken (partial treatment masks culture), recent catheterisation, allergy history, current medication that interacts with the planned antibiotic.
• Hygiene and products: soaps, douches, spermicide, tight clothing.
• Social: access to toilets and clean water, ability to return.

Examination

• Temperature, heart rate, blood pressure, respiratory rate, oxygen saturation, hydration.
• Abdomen: suprapubic tenderness, costovertebral angle tenderness (percussion), uterine tenderness and tone, fundal height, foetal heart.
• Genital examination: vulval erythema, ulcers, vesicles, warts, discharge, urethral meatus, urethral discharge or tenderness, Skene gland swelling, cystocele or prolapse.
• Speculum examination when discharge, bleeding or ruptured membranes are suspected.
• Bedside tests: urine dipstick, capillary glucose, and pregnancy related blood pressure and urine protein.

Red flags

• Fever of 38.0°C or more, rigors, loin pain, vomiting, or inability to keep fluids down (pyelonephritis).
• Signs of sepsis: heart rate over 120 beats/min, respiratory rate over 25 breaths/min, systolic pressure under 90 mmHg, confusion, oxygen saturation under 94%.
• Contractions, bleeding, leaking fluid or reduced foetal movements.
• Visible haematuria with colic (stone) or clots with retention.
• Failure to improve after 48 hours of treatment, or recurrence within 2 weeks.
• Diabetes, sickle cell disease, solitary kidney, renal transplant or immunosuppression.
• Genital ulcers or blisters (herpes) near term.
• Urinary retention, neurological symptoms, severe pain on passing urine with a swollen vulva.

Special groups. Women with diabetes and sickle cell trait have a higher risk of infection and progression. Women with renal transplant need specialist care and culture directed treatment. Postpartum women: catheterisation and instrumental delivery raise infection and retention risk. Region specific: schistosomiasis causes haematuria with dysuria in endemic areas.

Organised by site. Each cause is common unless marked serious or uncommon.

Bladder and urethra

• Acute cystitis.
• Asymptomatic bacteriuria (no symptoms, found on screening).
• Urethral syndrome and urethritis (chlamydia, gonorrhoea, Mycoplasma genitalium, ureaplasma).
• Interstitial cystitis (bladder pain syndrome), radiation or chemical cystitis.
• Bladder stone or foreign body.
• Urethral diverticulum, Skene gland infection.
• Urethral caruncle, prolapse.

Upper tract

• Serious: acute pyelonephritis.
• Serious: obstructing ureteric stone with infection.
• Renal or perinephric abscess.
• Papillary necrosis (sickle cell, diabetes, analgesic use).
• Renal tuberculosis, schistosomiasis.
• Ureteric dilatation of pregnancy with stasis.

Vulval and vaginal

• Vulvovaginal candidiasis.
• Bacterial vaginosis, trichomoniasis.
• Genital herpes (primary episode causes severe external dysuria and retention).
• Vulval dermatitis, lichen sclerosus, lichen planus, eczema, contact dermatitis.
• Vulval or vaginal trauma and lacerations, female genital cutting complications.
• Syphilitic chancre, chancroid.
• Atrophy (rare in pregnancy), breastfeeding related hypo oestrogenism postpartum.

Sexually transmitted and systemic

• Chlamydia, gonorrhoea, Mycoplasma genitalium.
• Serious: disseminated gonococcal infection.
• Herpes simplex and varicella zoster in the sacral dermatomes.
• HIV seroconversion illness.

Obstetric and surrounding structures

• Preterm labour with bladder irritation.
• Chorioamnionitis with bladder symptoms, ruptured membranes (leakage mistaken for dysuria).
• Fibroids or head of the foetus pressing on the bladder.
• Pelvic inflammatory disease, tubo ovarian abscess.
• Appendicitis, pelvic abscess, diverticulitis (urinary symptoms from adjacent inflammation).
• Round ligament and pelvic girdle pain.

Drugs and chemicals

• Cyclophosphamide, tiaprofenic acid, ketamine, NSAID related cystitis, and concentrated urine from dehydration.
• Spermicides, scented hygiene products, bubble bath.

Stepwise reasoning

1. Establish whether the picture is lower tract, upper tract or vulvovaginal.
2. Send a midstream urine culture before antibiotics.
3. Assess for sepsis and obstetric complications.
4. Test for sexually transmitted infection and herpes when discharge, ulcers or risk factors are present.
5. Choose an antibiotic for the likely organism and start it; adjust by sensitivity.

First line tests

• Urine dipstick: nitrite positive suggests Gram negative infection; leucocyte esterase suggests inflammation; blood and protein are common. A negative dipstick does not exclude infection in pregnancy, and urine culture is required regardless.
• Midstream urine culture: significant bacteriuria is 10^5 colony forming units/mL or more of a single organism (10^3 colony forming units/mL or more is accepted in a symptomatic woman). Group B streptococcus at any count is significant. A mixed growth suggests contamination.
• Urine microscopy: pyuria (10 or more leucocytes/mm3), bacteria, casts. Sterile pyuria suggests chlamydia, gonorrhoea, tuberculosis or stones.
• Screening for asymptomatic bacteriuria with a midstream culture at the booking visit (10 to 16 weeks), repeated if previously positive or in women at high risk.
• Full blood count, C reactive protein, creatinine, electrolytes, glucose, blood cultures if febrile.
• Cardiotocography and obstetric ultrasound for women with contractions or fever.

Targeted tests

• Renal ultrasound for pyelonephritis not improving at 48 to 72 hours, recurrent infection, haematuria, suspected stone or obstruction, or a history of renal disease. Hydronephrosis is common in pregnancy and mild dilatation is physiological. Low dose CT is a second line test for suspected stones when ultrasound is non diagnostic.
• Nucleic acid amplification tests for chlamydia and gonorrhoea (first void urine or vulvovaginal swab); herpes simplex polymerase chain reaction from lesions; swabs for trichomonas, bacterial vaginosis and candida.
• Syphilis serology, HIV test, and hepatitis B in women with new sexual exposure.
• Urine for schistosomiasis ova in endemic areas; early morning urine for acid fast bacilli in suspected renal tuberculosis.
• Urine glucose and haemoglobin electrophoresis where indicated.
• Test of cure culture 1 to 2 weeks after treatment of bacteriuria or infection, and monthly screening for the rest of pregnancy when recurrent.
• Urodynamic or urology work up is deferred until after pregnancy unless obstruction or retention occurs.

Limitations. Dipstick has a poor negative predictive value in pregnancy, and contamination is common. Culture takes 24 to 48 hours, so treatment starts empirically. Leucocytes in urine can come from vaginal discharge. Hydronephrosis of pregnancy is not by itself obstruction. Antibiotics before sampling reduce culture yield.

Immediate steps. Assess for sepsis. For fever with loin pain or systemic upset, admit, take cultures, and give intravenous antibiotics. For stable women with lower tract symptoms, send a culture, treat empirically, and arrange review with the result.

Symptom relief. Oral fluids to keep urine pale; paracetamol 1 g orally every 4 to 6 hours (maximum 4 g daily; 3 g with alcohol use, malnutrition or liver impairment); avoid NSAIDs from 20 weeks. Urinary alkalinisers (sodium citrate or potassium citrate sachets) give limited relief for cystitis and need monitoring of sodium and potassium; avoid in hypertension and renal impairment. Phenazopyridine has limited evidence and is avoided in the first trimester and in G6PD deficiency.

Asymptomatic bacteriuria and acute cystitis (oral antibiotics for 5 to 7 days, chosen by culture)

• Cefalexin 500 mg orally every 12 hours (or 500 mg every 6 hours in a heavier woman).
• Nitrofurantoin modified release 100 mg orally twice daily with food; avoid in the first trimester when other options exist, avoid at term (38 weeks onwards) and during labour (neonatal haemolysis), and avoid in G6PD deficiency and creatinine clearance under 45 mL/min.
• Amoxicillin 500 mg orally every 8 hours only if the isolate is sensitive (resistance is common).
• Co-amoxiclav 625 mg orally every 8 hours if the isolate is sensitive and others fail.
• Fosfomycin 3 g orally as a single dose is an alternative for cystitis (less evidence for asymptomatic bacteriuria).
• Trimethoprim 200 mg orally twice daily is avoided in the first trimester (folate antagonist) and, if used later, with folic acid 5 mg daily and only when the isolate is sensitive.
• Avoid tetracyclines, fluoroquinolones and sulphonamides near term.
• Group B streptococcus in urine at any count: treat with an oral antibiotic chosen by sensitivity and give intrapartum prophylaxis (benzylpenicillin 3 g intravenously, then 1.5 g every 4 hours until birth).
• Repeat culture 1 to 2 weeks after treatment; retreat by sensitivity if positive.

Acute pyelonephritis

• Admit; intravenous fluids and oxygen if needed.
• Ceftriaxone 1 to 2 g intravenously once daily, or cefuroxime 1.5 g intravenously every 8 hours; add gentamicin 5 mg/kg intravenously once daily (adjusted to renal function) for sepsis or a resistant organism; meropenem 1 g every 8 hours for extended spectrum beta lactamase producers.
• Switch to oral cefalexin 500 mg every 6 hours (or the antibiotic chosen by sensitivity) after 24 to 48 hours afebrile, completing 10 to 14 days.
• Antiemetic: ondansetron 4 mg orally or intravenously every 8 hours (maximum 16 mg daily); alternatively metoclopramide 10 mg every 8 hours for up to 5 days.
• Watch for pulmonary oedema and acute respiratory distress syndrome (endotoxin, fluid loading): give fluids in 250 to 500 mL boluses, measure input and output, and review the chest.
• Check blood count (anaemia and haemolysis), creatinine and cultures daily.
• If fever persists beyond 48 to 72 hours: ultrasound for obstruction or abscess, check the organism for resistance, and consider ureteric stent or percutaneous nephrostomy.
• Suppressive prophylaxis after one episode of pyelonephritis or two or more cystitis episodes: cefalexin 250 to 500 mg orally at night, or nitrofurantoin 50 to 100 mg orally at night until 2 weeks after birth (not near term), with monthly cultures.

Sexually transmitted infection and vulvovaginal causes

• Chlamydia: azithromycin 1 g orally as a single dose (or amoxicillin 500 mg orally three times daily for 7 days); test of cure at 4 weeks and retest at 3 months; treat the partner and avoid intercourse for 7 days.
• Gonorrhoea: ceftriaxone 1 g intramuscularly as a single dose (with azithromycin 1 g orally if chlamydia is not excluded); test of cure.
• Trichomoniasis: metronidazole 400 mg orally twice daily for 5 to 7 days (or 2 g as a single dose).
• Bacterial vaginosis: metronidazole 400 mg orally twice daily for 5 to 7 days.
• Vulvovaginal candidiasis: clotrimazole 500 mg pessary once at night, or clotrimazole 1% cream, for 7 days in pregnancy; oral fluconazole is avoided in pregnancy.
• Primary genital herpes: aciclovir 400 mg orally three times daily for 5 to 7 days (extend if new lesions continue), lidocaine 2% gel, urination in a warm bath, and catheterisation for retention; in the third trimester, aciclovir 400 mg three times daily from 36 weeks until birth for women with recurrent herpes, and plan caesarean section if a primary episode occurs within 6 weeks of birth. Seek specialist advice.
• Syphilis: benzathine benzylpenicillin 2.4 million units intramuscularly once for early disease (weekly for 3 weeks for late latent disease), with specialist input.

Stones. Hydration, analgesia (paracetamol, then a short course of an opioid such as oral morphine 5 to 10 mg), antiemetics, and antibiotics for infection; avoid NSAIDs from 20 weeks. Many small stones pass. For infection with obstruction, refer urgently for ureteric stent or percutaneous nephrostomy; ureteroscopy is possible in the second trimester; avoid lithotripsy.

Interstitial cystitis. Reassure, advise diet and fluid adjustment, bladder training, and specialist referral; intravesical therapy and strong analgesics are deferred.

Postpartum. Treat bacteriuria and cystitis with cefalexin 500 mg every 12 hours for 5 to 7 days; check residual volume by catheterisation or bladder scan after epidural, instrumental birth or retention (catheter for volumes over 150 mL); nitrofurantoin is acceptable in the breastfeeding woman with a healthy term infant.

Special groups. Diabetes: strict glucose control and a low threshold for culture and treatment. Sickle cell disease: treat early and screen monthly. HIV: treat bacteriuria with the same antibiotics as other women. Renal transplant: specialist care and drug level monitoring. Spinal cord injury and catheter use: prophylaxis and treatment chosen by culture. Region specific: where culture is unavailable, treat symptomatic women empirically with cefalexin or amoxicillin and treat for sexually transmitted infection if discharge or ulcers are present.

Monitoring. Temperature, pulse, blood pressure and fluid balance every 4 hours in pyelonephritis. Response to treatment within 48 hours. Culture 1 to 2 weeks after treatment, and monthly cultures when there has been pyelonephritis, recurrent infection, or suppressive therapy.

Referral and escalation. Refer to the obstetric team the same day for fever, loin pain, contractions, bleeding or sepsis. Refer to urology for obstruction, stones with infection, haematuria, and recurrent infection with anatomical abnormality. Refer to nephrology for renal disease, transplant or declining renal function. Refer to genitourinary medicine for sexually transmitted infection and herpes near term.

Admission criteria. Pyelonephritis (all cases in pregnancy initially), sepsis, vomiting preventing oral treatment, dehydration, suspected obstruction, contractions or ruptured membranes, diabetes or immunosuppression with systemic features, or failure of oral treatment at 48 hours.

Discharge and follow up. Discharge cystitis with treatment, a culture result plan and review in 1 week. Discharge pyelonephritis when afebrile for 24 to 48 hours with oral treatment tolerated, then review in 1 week with repeat culture and arrange suppressive treatment. Plan routine culture at each trimester for women with previous infection.

Safety netting. Return at once for fever, shivering, loin pain, vomiting, contractions, bleeding, leaking fluid, reduced foetal movements, or symptoms not improving within 48 hours.