Pregnancy, Urinary Tract Infections

Author: Allison M Loynd, DO, Resident Physician, Department of Emergency Medicine, Wayne State University School of Medicine, Detroit Receiving Hospital
Coauthor(s): Adam J Rosh, MD, Assistant Professor, Department of Emergency Medicine, Wayne State University/Detroit Receiving Hospital

Introduction

Background

Urinary tract infections (UTIs) are one of the most common bacterial infections during pregnancy. UTIs are associated with risks to both the fetus and the mother, including pyelonephritis , preterm birth, low birth weight, and increased perinatal mortality. The prevalence rates of bacteriuria in pregnant women and nonpregnant women are essentially the same.1 UTIs are more common in women when compared with men, primarily because of the anatomic differences of the shorter urethra and its proximity to the vagina and the rectum. However, when pregnant women have a urinary tract infection, they have a higher risk for and increased occurrence of upper tract UTIs when compared with lower tract UTIs.

Several physiologic changes occur during pregnancy that cause otherwise healthy women to be more susceptible to serious sequelae from urinary tract infections.2 The infections can be symptomatic or asymptomatic. Asymptomatic bacteriuria, as the name implies, is a positive urine culture without specific symptoms. Asymptomatic bacteriuria increases the risk for an upper tract UTI, also known as pyelonephritis. Treatment of asymptomatic bacteriuria reduces the risk of a symptomatic infection.3

Pathophysiology

Remarkable changes occur in the structure and function of the urinary tract during pregnancy. Blood-volume expansion is accompanied by increases in the glomerular filtration rate (GFR) and urinary output. The ureters undergo tonic relaxation because of the mass production of hormones, particularly progesterone. This loss in tone, along with the increased urinary tract volume, results in urinary stasis, which, in turn, can lead to dilatation of the ureters and the calyceal pelves. Urinary stasis and the presence of vesicoureteral reflux predispose some women to upper tract UTIs and acute pyelonephritis .

Frequency

United States

The frequency of asymptomatic bacteriuria occurs in 2-7% of pregnancies, similar to the nonpregnant population. However, up to 40% of these may progress to symptomatic upper tract UTI or pyelonephritis, significantly more than in nonpregnant women.4 Several factors are associated with an increased frequency in various patient populations. Indigent patients have a 5-fold increased incidence of bacteriuria compared with that of nonindigent patients. The risk is doubled in women with sickle cell trait. Other risk factors for bacteriuria include diabetes mellitus , neurogenic bladder retention , and a history of previous urinary tract infections.

Mortality/Morbidity

Untreated upper tract UTIs are associated with low birth weight, prematurity, premature labor , hypertension, preeclampsia , maternal anemia, and amnionitis.5 A retrospective population-based study by Mazor-Dray et al showed that urinary tract infection during pregnancy is independently associated with intrauterine growth restriction, preeclampsia, preterm delivery, and cesarean delivery.6

Race

When socioeconomic status is controlled, no significance difference among the races seems to exist.

Sex

Urinary tract infections (UTIs) are 14 times more frequent in women than in men. This difference is attributed to several factors: (1) the urethra is shorter in women; (2) in women, the lower third of the urethra is continually contaminated with pathogens from the vagina and the rectum; (3) women tend not to empty their bladders as completely as men; and (4) exposure of the urogenital system to bacteria during intercourse.

Clinical

History

The presentation varies depending on whether the patient has asymptomatic bacteriuria, a lower tract UTI (cystitis), or an upper tract UTI (pyelonephritis).

  • Pregnant women with asymptomatic bacteriuria usually are diagnosed incidentally on routine urinalysis and urine culture.
  • Burning with urination (dysuria) is the most significant symptom in pregnant women with symptomatic cystitis.
  • The usual complaints of increased frequency, nocturia, and suprapubic pressure are not particularly helpful, because most pregnant women experience these as a result of increased pressure from the growing uterus.
  • Symptoms of pyelonephritis include the following:
    • Fever (Often, the temperature is very high.)
    • Chills
    • Nausea and vomiting
    • Costovertebral angle (CVA) or flank pain

Physical

A thorough physical examination is recommended, with particular attention to the abdomen.

  • CVA tenderness may be present.
  • Suprapubic tenderness may be present.
  • The fetal heart rate should be noted.
  • Pelvic examination is strongly recommended in all patients (with the exception of the third-trimester patient with bleeding) to rule out vaginitis or cervicitis .

Causes

  • Escherichia coli (most common, in as many as 70% of cases)
  • Group B Streptococcus (10%)
  • Klebsiella or Enterobacter species (3%)
  • Proteus species (2%)3

Differential Diagnoses

Cervicitis
Renal Calculi
Sexually transmitted infection (GC, NGU, HSV, trichomoniasis)
Urethritis
Vaginitis

Other Problems to Be Considered

Pyelonephritis

Workup

Laboratory Studies

  • In all pregnant patients, a urine specimen should be carefully collected for urinalysis and culturing during the first prenatal visit or at 12-16 weeks' gestation.
    • These tests help to identify patients with asymptomatic bacteriuria as well as those with other specific complaints.
    • For urine collection, a midstream clean catch is adequate, provided the patient is given careful instructions.
    • Catheterization is indicated if the patient is unable to void, too ill, extremely obese, or bedridden.
    • Two consecutive voided specimens with isolation of the same bacterial strain (100,000 CFU/mL) or a single catheterized specimen (100 CFU/mL) is diagnostic.7 ,2
    • Counts of less than 100,000 CFU/mL, with 2 or more organisms, usually indicate a contamination rather than an infection.
    • The leukocyte esterase test of the urine can be used as a screening examination for pyuria, although this test may be unreliable in patients with low-level pyuria (5-20 WBCs per high-power field).
  • Patients with pyelonephritis often have WBC casts.
  • Urine culturing should be performed in cases of suspected acute pyelonephritis, patients requiring hospitalization, and patients with a history of recent instrumentation or repeated infections.
  • CBC, electrolyte, blood urea nitrogen (BUN), and creatinine tests should be ordered at the physician's discretion, although the results do not aid in the diagnosis or change treatment unless they are markedly abnormal.

Imaging Studies

  • Unless anatomic abnormalities or renal disease is suspected, routine imaging studies are not necessary.
  • In cases of persistent symptoms, persistent infection, or suspected urolithiasis , renal ultrasonography may be helpful.

Treatment

Emergency Department Care

Because of the dangers of maternal and fetal complications, care in the ED should be focused on identifying and treating patients with asymptomatic and symptomatic bacteriuria. Treatment of asymptomatic bacteriuria in pregnant patients is important because of the increased risk of urinary tract infection (UTI) and its associated sequelae.8 ED care may involve the following:

  • Administration of appropriate antibiotics
  • Administration of fluid if the patient is dehydrated
  • Admission if any indication of UTI involvement exists

Consultations

An obstetrician may be consulted.

Medication

Antibiotic therapy for urinary tract infection should be initiated after all necessary cultures are obtained. If significant nausea or pain is present, appropriate medication may be indicated. Treatment of all symptomatic and asymptomatic patients with bacteriuria is important.

Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Empiric coverage for E coli and Klebsiella, Proteus, and Enterobacter species should be provided.3

Penicillins and cephalosporins are safe for use during pregnancy. Ceftriaxone should be withheld close to parturition due to the possibility of neonatal kernicterus secondary to bilirubin displacement. Trimethoprim is a folic acid antagonist and should be avoided, especially during the first trimester. Fluoroquinolones and tetracyclines are known teratogens and are contraindicated in pregnancy.

 

Amoxicillin (Amoxil, Polymox, Trimox)

DOC and interferes with the synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible bacteria.

Adult

Asymptomatic bacteriuria (ASB): 500 mg PO tid for 3 d
Acute cystitis: 250-500 mg PO q8h for 10 d
Acute pyelonephritis: 1-2 g PO q6h plus gentamicin, 1 mg/kg PO q8h

Pediatric

20-50 mg/kg/d PO divided q8h

Reduces the efficacy of oral contraceptives

Documented hypersensitivity

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Reduces efficacy of oral contraceptives; adjust dose in renal impairment; may enhance chance of candidiasis

 

Nitrofurantoin (Macrobid, Furadantin)

Synthetic nitrofuran that interferes with bacterial carbohydrate metabolism by inhibiting acetylcoenzyme A. Bacteriostatic at low concentrations (5-10 mcg/mL) and bactericidal at higher concentrations.

Adult

ASB or cystitis: 100 mg PO bid for 5-7 d
Recurrent infections: 100 mg PO q6h for 21 d

Pediatric

5-7 mg/kg/d PO divided q6h

Anticholinergics may delay gastric emptying and increase absorption, increasing bioavailability; antacids made of magnesium salts may decrease effects, decreasing absorption; high doses of concurrent probenecid decreases renal clearance and increases nitrofurantoin toxicity

Documented hypersensitivity; renal insufficiency (<60 mL/min CrCl); anuria; oliguria

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

May cause severe and irreversible peripheral neuropathy that can be fatal; renal impairment, diabetes, electrolyte imbalance, anemia, and vitamin B deficiency increase risk for adverse effects; prolonged use of antibiotics may result in fungal or bacterial overgrowth of resistant or nonsusceptible organisms

 

Trimethoprim and sulfamethoxazole (Bactrim, Septra)

Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Antibacterial activity of TMP-SMZ includes common urinary tract pathogens, except Pseudomonas aeruginosa .

Adult

ASB or cystitis: 160/800 mg PO q12h for 10 d
Pyelonephritis: 160/800 mg PO q12h

Pediatric

<2 months: Do not administer
>2 months: 15-20 mg/kg/d, based on TMP dose, PO tid/qid for 14 d

May increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration with dapsone may increase blood levels of both drugs; coadministration of diuretics increases incidence of thrombocytopenia purpura in elderly patients; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine

Documented hypersensitivity; megaloblastic anemia due to folate deficiency

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Discontinue at first appearance of skin rash or sign of adverse reaction; obtain CBCs frequently; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; prolonged IV infusions or high doses may cause bone marrow depression (if signs occur, give 5-15 mg/d leucovorin); caution in folate deficiency (eg, patients with chronic alcoholism, elderly patients, those receiving anticonvulsant therapy, or those with malabsorption syndrome); hemolysis may occur in G-6-PD deficient individuals; AIDS patients may not tolerate or respond to TMP-SMZ; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); give fluids to prevent crystalluria and stone formation

 

Cephalexin (Keflex)

First-generation cephalosporin arrests bacterial growth by inhibiting bacterial cell wall synthesis. Bactericidal activity against rapidly growing organisms. Primary activity against skin flora. Used for skin infections or prophylaxis in minor procedures.

Adult

ASB: 250 mg PO q6h for 3 d
Cystitis: 250-500 mg PO q6h for 10 d

Pediatric

25-50 mg/kg/d PO q6h; not to exceed 3 g/d

Coadministration with aminoglycosides increase nephrotoxic potential

Documented hypersensitivity

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal impairment

 

Cefpodoxime (Vantin)

Third-generation cephalosporin with broad-spectrum gram positive and gram-negative activity. Arrests bacterial growth by binding to one or more penicillin-binding proteins thus inhibiting bacterial cell wall synthesis.

Adult

ASB or cystitis: 100 mg PO bid for 7d

Pediatric

5 mg/kg/d PO q12h for 5 d

Coadministration with probenecid, aminoglycosides (gentamicin), cyclosporine, or diuretics (furosemide, hydrochlorothiazide) may increase nephrotoxicity

Documented hypersensitivity

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal impairment

 

Ceftriaxone (Rocephin)

Third-generation cephalosporin with broad-spectrum gram-negative activity. Lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins.

Adult

Acute pyelonephritis: 1-2 g IV q24h

Pediatric

50-75 mg/kg/d IV divided q12h; not to exceed 2 g/d

Probenecid may increase levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity

Documented hypersensitivity

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal impairment; caution in breastfeeding women and allergy to penicillin

 

Cefazolin (Ancef)

First-generation semi-synthetic cephalosporin that arrests bacterial cell wall synthesis, inhibiting bacterial growth. Primarily active against skin flora, including Staphylococcus aureus . Typically used alone for skin and skin-structure coverage. IV and IM dosing regimens are similar.

Adult

1-2 g IV/IM q8h

Pediatric

25-100 mg/kg/d IV/IM divided q6-8h depending on the severity of the infection; not to exceed 6 g/d

Probenecid prolongs effect; coadministration with aminoglycosides may increase renal toxicity; may cause false-positive results at urine dip testing for glucose

Documented hypersensitivity

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal impairment; superinfections and promotion of nonsusceptible organisms may occur with prolonged use or repeated therapy

 

Cefuroxime (Ceftin)

Second-generation cephalosporin maintains gram-positive activity that first-generation cephalosporins have. Adds activity against Proteus mirabilis, Haemophilus influenzae, E coli, Klebsiella pneumoniae, and Moraxella catarrhalis . Condition of patient, severity of infection, and susceptibility of microorganism determines proper dose and route of administration.

Adult

Acute pyelonephritis: 750-1500 mg IV/IM q8h
250-500 mg PO bid

Pediatric

Not established

Disulfiram-like reactions may occur when alcohol is consumed within 72 h after administration; may increase hypoprothrombinemic effects of anticoagulants; may increase nephrotoxicity in patients receiving potent diuretics such as loop diuretics; coadministration with aminoglycosides increase nephrotoxic potential

Documented hypersensitivity

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Administer half dose if creatinine clearance is 10-30 mL/min and quarter dose if it is <10 mL/min; fungal and microorganism overgrowth may occur with prolonged therapy

 

Ceftibuten (Cedax)

By binding to one or more of the penicillin-binding proteins, arrests bacterial cell wall synthesis and inhibits bacterial growth.

Adult

400 mg PO daily

Pediatric

Not established

Follow-up

Further Inpatient Care

  • The treatment of pregnant women with acute pyelonephritis may involve the following:
    • Hospitalization
    • Frequent monitoring of vital signs
    • Evaluation of CBC, serum creatinine, and electrolyte levels
    • Urine and blood culturing
    • Monitoring of urine output (with a catheter, if necessary)
    • Administration of intravenous crystalloid fluid to maintain a minimum urinary output of more than 30 mL/h
    • Administration of intravenous antimicrobial agent
    • Use of antipyretics, if temperature is higher than 39°C

Further Outpatient Care

  • Appropriate antibiotics may be required for UTIs during pregnancy.
  • Advise the patient to maintain adequate fluid intake.
  • The obstetrician who is providing prenatal care should perform follow-up within 1 week for repeat urinalysis.
  • Patients should be instructed to return to the ED if symptoms or fever worsens or if they are unable to tolerate oral medications for any reason.

Complications

  • Complications of pyelonephritis during pregnancy can be devastating.8 No evidence suggests that antimicrobial resistance is related to more severe infections. Although complications such as pyonephrosis and perinephric abscesses most often occur in patients with obstruction, they are not prerequisites for severe complications.
  • Complications may include the following:
    • Perinephric cellulitis and abscess
    • Septic shock
    • Renal dysfunction (usually transient, but as many as 25% of pregnant women with pyelonephritis have a decreased GFR)
    • Hematologic dysfunction (common but seldom of clinical importance)
    • Pulmonary injury (Approximately 1 in 50 women with severe pyelonephritis during pregnancy have evidence of pulmonary injury and respiratory insufficiency. Endotoxins that alter alveolar-capillary membrane permeability are produced; subsequently, pulmonary edema and acute respiratory distress syndrome develop.)
    • Premature delivery leading to increased infant morbidity and mortality.

Prognosis

  • The prognosis of urinary tract infection (UTI) in pregnancy is good with appropriate therapy.

References

  1. [Guideline] American Academy of Pediatrics and American College of Obstetricians and Gynecology. Guidelines for Perinatal Care. American Academy of Pediatrics. 6th ed. 2007.

  2. Duarte G, Marcolin AC, Quintana SM, Cavalli RC. [Urinary tract infection in pregnancy]. Rev Bras Ginecol Obstet . Feb 2008;30(2):93-100. [Medline] .

  3. [Guideline] Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis . Mar 1 2005;40(5):643-54. [Medline] .

  4. Smaill F. Asymptomatic bacteriuria in pregnancy. Best Pract Res Clin Obstet Gynaecol . Jun 2007;21(3):439-50. [Medline] .

  5. Hill JB, Sheffield JS, McIntire DD, Wendel GD Jr. Acute pyelonephritis in pregnancy. Obstet Gynecol . Jan 2005;105(1):18-23. [Medline] .

  6. Mazor-Dray E, Levy A, Schlaeffer F, Sheiner E. Maternal urinary tract infection: is it independently associated with adverse pregnancy outcome?. J Matern Fetal Neonatal Med . Feb 2009;22(2):124-8. [Medline] .

  7. Vazquez JC, Villar J. Treatments for symptomatic urinary tract infections during pregnancy. Cochrane Database Syst Rev . 2000;CD002256. [Medline] .

  8. Gilstrap LC 3rd, Ramin SM. Urinary tract infections during pregnancy. Obstet Gynecol Clin North Am . Sep 2001;28(3):581-91. [Medline] .

  9. Krcmery S, Hromec J, Demesova D. Treatment of lower urinary tract infection in pregnancy. Int J Antimicrob Agents . Apr 2001;17(4):279-82. [Medline] .

  10. Lucas MJ, Cunningham FG. Urinary infection in pregnancy. Clin Obstet Gynecol . Dec 1993;36(4):855-68. [Medline] .

  11. Manka W, Solowiow R, Okrzeja D. Assessment of infant development during an 18-month follow-up after treatment of infections in pregnant women with cefuroxime axetil. Drug Saf . Jan 2000;22(1):83-8. [Medline] .

  12. Miller JM, Raimer KA. Urinary tract infection and pyelonephritis in pregnancy. In: Obstetrics and Gynecologic Infectious Disease . 1994:283-93.

  13. Schieve LA, Handler A, Hershow R, Persky V, Davis F. Urinary tract infection during pregnancy: its association with maternal morbidity and perinatal outcome. Am J Public Health . Mar 1994;84(3):405-10. [Medline] .

  14. Sweet RL, Gibbs RS. Urinary tract infection. In: Infectious Disease of the Female Genital Tract . 3rd ed. 1995:429-64.

  15. Zinner SH. Management of urinary tract infections in pregnancy: a review with comments on single dose therapy. Infection . 1992;20 Suppl 4:S280-5. [Medline] .

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