Treatment of Urinary Tract Infections in Pregnancy 

SUMMARY:   

Urinary tract infections (UTIs) are one of the most common infections in pregnancy, occurring in about 8% of all pregnancies and range from asymptomatic bacteriuria to acute pyelonephritis. They are associated with adverse pregnancy outcomes such as preterm birth and low birth weight, therefore the timely identification and treatment of these is essential. Anatomic changes during pregnancy increase the risk for UTIs, such as ureteral dilation, the mechanical compression of ureters by the uterus causing urinary stasis, contributing to bacteria colonization and ascending infection. E coli remains the most common identified pathogen. Given the high rates of antibiotic resistance to this organism, the selection of first line therapy must avoid antibiotics such as  amoxicillin and ampicillin. Treatment of symptomatic bacteriuria decreases the risk of pyelonephritis, which can cause significant maternal complications such as DIC and ARDS, as well as fetal complications such as preterm birth. Patients with hemoglobinopathy have higher rates of cystitis and asymptomatic bacteriuria. ACOG provides recommendations regarding urinary tract infection in pregnancy.

Recommendations  

Asymptomatic Bacteriuria (ASB) 

• Screen once early in pregnancy  
• If culture ≥100,000 CFU/mL treatment should be started with antiobiotics adjusted once culture results are available if necessary 
  • Cephalexin: 250 to 500 mgs q6hr po 5 to 7 days  
  • Fosfomycin: 3 g po once  
  • Amoxicillin: 500 mg po q8hr for 5 to 7 days | 875 mg po q12hr for 5 to 7 days | Avoid starting prior to culture results due to high resistance  
  • Amoxicillin-clavulanate: 500 mg po q8hr for 5 to 7 days | 875 mg po q12hr for 5 to 7 days | Avoid starting prior to culture results due to high resistance 
  • ‘Reasonable to offer’ if no other alternatives available  
    • Nitrofurantoin: 100 mgs q12hr po 5 to 7 days 
    • Sulfamethoxazole-trimethoprim: 800/160 mgs q12hrs po 5o to 7 days 
  • Insufficient evidence for repeat screening following treatment  
• Presence of Group B strep 
  • Treat if ≥100,000 CFU/mL 
  • If <100,000 CFU/mL do not treat but it is an indication for group B streptococcus prophylaxis at the time of delivery 

Note: Low risk for anaphylaxis, cephalosporin treatment is appropriate | High risk for anaphylaxis should be treated with alternative regimen  

Acute Cystitis 

• Initiate treatment for symptomatic relief based on the following  
  • Clinical signs: Dysuria | Hematuria | Frequency | Nocturia  
  • Urinalysis: Consistent with UTI 
• Confirmed by urine culture of ≥100,000 organisms  
• Treatment regimen is the same as ASB  (see above) 
  • If symptoms persist  
    • Repeat cultures  
    • Consider daily prophylaxis preferably single daily dose if recurrent infection (≥2 UTIs during pregnancy)  

Pyelonephritis 

• Signs and symptoms  
  • Fever ≥38° degrees C | Nausea and vomiting  
  • Flank pain | CVA tenderness | Renal ultrasonography abnormalities  
  • CBC: Leukocytosis | Bandemia | thrombocytopenia | Anemia  
  • Abnormal urinalysis  
  • May present with preterm labor or severe sequelae (e.g., sepsis)  

Note: Remain suspicious even if only some of the above is present (e.g., fever and UTI)  

• Inpatient treatment recommended for fluid hydration and empiric antibiotics   
• Start parenteral antibiotics prior to culture report  
  • Ampicillin 2g IV q6hr and gentamycin 1.5 mg/kg q8hr or 5 mg/kg IV q24hr 
  • Ceftriaxone 1g IV q24hr 
  • Aztreonam (can be used with beta-lactam allergy) 1g IV q8 to 12hr  
  • Cefepime 1g IV q12hr 

• Adjust antibiotics as needed after urine culture results are available    
• 14 day total course of therapy 
• Follow up suppressive therapy may be considered  

KEY POINTS:   

• Asymptomatic bacteriuria 
  • Screen as early as possible 
  • No evidence for repeating screening during pregnancy, including diabetes or spinal cord injury  
  • Routine dipsticks are not clinically useful and do not detect ASB 
  • A midstream urine culture is recommended 
    • Clean catch specimens do not decrease perineal contamination 
  • Do not treat normal vulvovaginal flora such as
    • Lactobacilli | Corynebacteria species | Coagulase-negative Staphylococcus 
• Cystitis
  • Leukocyte esterase or pyuria has a 97% sensitivity but not specific, due to white cells normally found in vagina/vulva 
  • Nitrates are 94 to 98% specific, but not all bacteria produce nitrates 
  • Use of antibiotics should be guided by sensitivities and safety profiles 
  • Nitrofurantoin is a reasonable first line treatment choice 
    • Patients with known G6PD deficiency should avoid this antibiotic  
  • Recurrent UTIs occur in 4% to 5% of pregnancies and suppressive regimens include 
    • Nitrofurantoin: 100 mg daily  
    • Cephalexin 250 to 500 mg daily  
• Pyelonephritis 
  • Can cause preterm labor, labor, ARDS, sepsis, acute renal insufficiency 
  • Differential diagnosis includes  
    • Nephrolithiasis 
    • Chorioamnionitis 
    • Renal abscess 
    • Urosepsis without pyelonephritis 
  • Blood cultures may not be clinically useful 
  • Majority of patients have clinical improvement in 48 to 72 hours 
  • Recurrent pyelonephritis occurs in 25% of patients before delivery 
  • Consideration of a daily suppressive therapy is the same as for cystitis 

Primary Sources – Learn More  

ACOG Clinical Consensus 4: Urinary Tract Infections in Pregnant Individuals 

American Urological Association Guidelines for Recurrent Uncomplicated Urinary Tract Infections in Women

SUMMARY:

Urinary tract infections (UTIs) are a common condition in women. 60% of women will experience at least one UTI in their lifetime, with a fraction of them experiencing recurrent UTIs. Recurrent urinary tract infections are defined by two separate culture proven episodes of symptomatic acute bacterial cystitis within 6 months, or three episodes in one year.

Note: These guidelines do not apply to patients who are pregnant, immunocompromised, those with any abnormalities of the urinary tract, who show signs or symptoms of systemic bacteremia, or those who self-catheterize or have indwelling catheters

Evaluation

• Document positive urine cultures in prior episodes to establish diagnosis of recurrent UTI
• Perform complete history and physical, including a pelvic examination
• If urine specimen is suspected to be contaminated
  • Repeat urine studies, potentially with a catheterized specimen
• Do not routinely obtain cystoscopy and imaging in the workup of recurrent UTI
• Perform urinalysis, urine culture, and sensitivity with every symptomatic cystitis episode before starting treatment
• Self-start treatment while awaiting culture results
  • Can be offered to certain patients with acute episodes after a urine culture has been collected

Asymptomatic Bacteriuria

• If patient is asymptomatic, urine testing should not be performed
• Asymptomatic bacteriuria should not be treated

Antibiotic Treatment

• First line antibiotics: Nitrofurantoin | TMP-SMX | Fosfomycin
  • Use of fluoroquinolones and cephalosporins have been linked to increased antibiotic resistance
• Antibiotics should be chosen based on local resistance
• Recurrent UTIs should be treated with as short a duration of antibiotics as possible | Maximum 7 days
• If urine culture is resistant to oral antibiotics
  • Treat with parental antibiotics for as short a course possible | Maximum 7 days

Prophylaxis

• Antibiotic prophylaxis to decrease recurrent of future UTIs
  • Reasonable after shared decision making with patient
• Cranberry prophylaxis can be offered
• In peri- and post- menopausal women with recurrent UTIs
  • Vaginal estrogen therapy can reduce the risk of future UTIs if no contraindications

Follow Up

• Test of cure should not be performed if patient is asymptomatic
• If symptoms persist after treatment with antibiotics, repeat urine cultures should be performed

Learn More – Primary Sources

AUA: Recurrent Uncomplicated Urinary Tract Infections in Women

Uncomplicated Cystitis: When to Culture, How to Treat and Recommended Prevention Strategies

CLINICAL ACTIONS:

Acute uncomplicated cystitis is often readily recognized by patients as a routine bladder infection.  Uncomplicated cystitis rarely progresses to pyelonephritis and urosepsis even if untreated. The primary goal of treatment is to relieve symptoms. If a patient presents with pain, urgency and frequent urination

• Determine if a patient may have pyelonephritis as urine cultures are indicated in all cases of upper urinary tract infection (UTI)
  • Culture: Costo-vertebral angle tenderness | Fever | Chills | Flank pain | Nausea/ vomiting | Recurrent/ persistent symptoms despite treatment
• In the absence of signs and/or symptoms of pyelonephritis, cultures are not required
• Consider urinalysis in specific circumstances such as
  • Postmenopausal women who may have intermittent dysuria or urge incontinence without infection
  • Women without a previous history of UTI

• Women with previous history and recognize UTI symptoms can be treated empirically without urinalysis

Antibiotic Therapy

Note: The following recommendations apply to nonpregnant women | There has been concern regarding the use of nitrofurantoin and sulfonamides in the first trimester due to possible risk for birth defects

• First-line therapy 
  • Trimethoprim-Sulfamethoxazole (TMP-SMX) 160-800 mg PO BID x 3 days
  • Fosfomycin 3 gm PO single dose
  • Nitrofurantoin 100 mg PO BID x 5 days
  • Consider beta-lactam for pregnant patients
• Fluoroquinolones: Reserved for situations in which other agents are not appropriate  
  • Ciprofloxacin 250 mg BID x 3 days
  • Levofloxacin 250 mg BID x 3 days

Note: FDA recommends the following

FDA has approved label changes that reserve the use of fluoroquinolone antibacterial medicines when treating acute bacterial sinusitis (ABS), acute bacterial exacerbation of chronic bronchitis (ABECB), and uncomplicated urinary tract infections (UTI) for patients who do not have alternative treatment options

SYNOPSIS:

UTI is the most common infection encountered in the outpatient setting. By age 32, half of all women will have had at least one UTI. Recurrence rates are over 25%. Fluoroquinolones are effective, but the recommendation is to avoid as a first-line medication to prevent future resistance and maintain these medications as a second-line treatment when needed.

KEY POINTS:

• Risk factors include
  • Sexual intercourse | Use of spermicides and diaphragm | Previous UTI | New sexual partner | Increasing parity | Diabetes | Obesity | Kidney stones | indwelling catheter
  • With increasing age, consider vaginal atrophy, pelvic organ prolapse and bladder retention

• No association between
  • Pre/ postcoital voiding | Daily beverage consumption | Frequency of urination | Delayed urination | Wiping patterns | Tampon use | Douching | Hot tub use | Type of underwear

• Consider formal urologic evaluation for women with
  • Persistent hematuria | Multiple early recurrences of cystitis with the same bacteria

• Patients with pyelonephritis with severe/worsening illness or persistent fever 48 to 72 hours after initiation of antibiotics
  • Image to evaluate for stone, abscess or obstruction
• Treatment of uncomplicated cystitis should take into consideration local antimicrobial resistance patterns
  • Resistance rates higher than 15 to 20% will require a change in antibiotic class
  • Beta-lactams such as cephalosporins and amoxicillin are less effective due to increasing resistance
• Nonantimicrobial prevention of recurrent UTI
  • Change spermicides or consider other birth control option | Topical estrogen if menopausal (local may be more beneficial than oral)

• Note: Do not screen or treat asymptomatic bacteriuria in nonpregnant, premenopausal women

Learn More – Primary Sources:

CDC: Adult Outpatient Treatment Recommendations | Antibiotic Use

ACP: Appropriate Use of Short-Course Antibiotics in Common Infections

USPSTF: Screening for Asymptomatic Bacteriuria in Adults

FDA Drug Safety Communication: FDA updates warnings for oral and injectable fluoroquinolone antibiotics due to disabling side effects