Uncomplicated cystitis in pregnancy

Background:

Studies in the UK have shown that asymptomatic bacteriuria (persistent colonisation of the urinary tract without urinary symptoms) occurs in 4% of pregnant women (1)

• unless detected and treated early, there is an increased risk of preterm birth and pyelonephritis affecting maternal and fetal outcome
• in about 30% of patients acute pyelonephritis occurs, especially at the time of deliver
• has been reported that 20-40% of pregnant women with untreated bacteriuria will develop pyelonephritis
• in pregnancy, routine and sensitive urinary screening programmes are essential for the detection of bacteriuria in pregnancy. The screening can be done by mid-stream urine culture early in pregnancy. The presence of >=10^8 cfu/L (>=10^5 cfu/mL) in asymptomatic, pregnant women indicates infection but should be confirmed in a repeat sample

Management: (2) (3)

• if the women has fever or loin tenderness
  • suspect upper urinary tract infection and admit or seek urgent specialist opinion
• give paracetamol for symptomatic relief
• do not recommend urine alkalinizing agents or cranberry products
  
  
• prescribe antibiotics empirically
  • refer to local guidelines
    • send midstream urine for culture and susceptibility
    • immediate antibiotic should be offered
      
      
    • with all antibiotic prescriptions, advise:
      • possible adverse effects of antibiotics include diarrhoea and nausea
      • seeking medical help if symptoms worsen at any time, do not improve within 48 hours of taking the antibiotic, or the person becomes very unwell
        
        
    • reassess at any time if symptoms worsen rapidly or significantly or do not improve in 48 hours of taking antibiotics, sending a urine sample for culture and susceptibility if not already done. Take account of:
      • other possible diagnoses
      • any symptoms or signs suggesting a more serious illness or condition
      • previous antibiotic use, which may have led to resistance
        
        
    • refer to hospital if a person aged 16 or over has any symptoms or signs suggesting a more serious illness or condition (for example, sepsis) Choice of antibiotic: (2) (3)
      • pregnant women with a lower UTI
        • Based on evidence, experience and resistance data, the committee agreed to recommend usual dose nitrofurantoin as the first-choice antibiotic (with the cautions outlined below):
          • nitrofurantoin is not recommended at term in pregnancy because it may produce neonatal haemolysis
            
            
          • trimethoprim was not recommended by NICE because it is contraindicated in pregnancy
            • trimethoprim is a folate antagonist and there is a teratogenic risk in the first trimester (BNF, August 2018).
              • however, the committee acknowledged that trimethoprim is sometimes used in pregnancy - if used in first trimester then also give folic acid 5 mg daily
                
                
        • First choice for treating lower UTI 3
          • nitrofurantoin (avoid at term) - if eGFR >=45 ml/minute
            • 100 mg modified-release twice a day for 7 days
              
              
        • Second choice for treating lower UTI (no improvement in lower UTI symptoms on first choice taken for at least 48 hours or when first choice not suitable)3, 6
          • amoxicillin (only if culture results available and susceptible)
            • 500 mg three times a day for 7 days OR
              
          • cefalexin
            • 500 mg twice a day for 7 days OR
          • alternative second choices
            • Consult local microbiologist, choose antibiotics based on culture and susceptibility results
              
              

Quinolones and tetracyclines should be avoided as empirical treatments. There are concerns about use of sulphonamides and trimethoprim in pregnancy:

• trimethoprim - theoretical teratogenic risk (folate antagonist); manufacturers advise avoid; BNF states first trimester is the trimester of risk.
  • trimethoprim 200 mg twice daily, for 7 days (off-label use)
    • give folic acid 5 mg daily if it is the first trimester of pregnancy
    • do not give trimethoprim if the woman is folate deficient, taking a folate antagonist, or has been treated with trimethoprim in the past year.
• sulphonamides - neonatal haemolysis and methaemaglobinaemia; BNF states third trimester is trimester of risk
• tetracyclines - avoid use during pregnancy; effects on skeletal development in animal studies if used during first trimester; dental discoloration and maternal hepatoxicity may occur if used during second or third trimesters
• quinolones - should be avoided during pregnancy; arthropathy in animal studies

Nitrofurantoin should not be used at term because of the risk of neonatal haemolysis - during the last few weeks may precipitate haemolytic anaemia due to glucose-6-phosphate dehydrogenase deficiency in the newborn

• BNF states third trimester is the trimester of risk associated with nitrofurantoin use

Consult local microbiology advice and latest edition of BNF for up-to-date guidance before definitive treatment.

Notes:

• about 1-2% of pregnant women suffer an acute lower UTI (cystitis) or upper UTI (pyelonephritis), with the former being more common
  • the most common infecting organisms is Escherichia coli (75-90 per cent); other infecting organisms include Proteus, Klebsiella, coagulase-negative staphylococci and Pseudomonas
• when the pregnant mother is very ill with acute pyelonephritis then there is a risk of preterm labour and even foetal loss. Thus hospital admission is recommended for these patients with intravenous antibiotics, hydration and analgesia. Treatment should be continued for two or three weeks
• about 15 % of women will have a recurrent UTI during pregnancy. Sometimes, a continuous low-dose prophylaxis throughout pregnancy is required in some women with recurrent UTI. These women require renal tract ultrasound scans, and review by a nephrologist or a urologist postnatally

Complications of untreated asymptomatic bacteriuria in pregnancy include pyelonephritis (in up to 40% of women), preterm delivery and infants with low birth weight, and anaemia. (4)

Reference:

1. Public Health England. 2018. SMI B41: UK Standards for Microbiology 640 Investigations-Investigation of urine. United Kingdom
2. Public Health England. Urinary tract infection: diagnostic tools for primary care. October 2020
3. Scottish Intercollegiate Guidelines Network. Management of suspected bacterial lower urinary tract infection in adult women. Sep 2020
4. Smaill FM, Vazquez JC. Antibiotics for asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev. 2019 Nov