AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Background

Urinary tract infections (UTIs) are the most common bacterial infections during pregnancy. They are associated with risk to the fetus and the mother. Pregnancy itself does not predispose women to UTIs. The prevalence rates of bacteriuria in pregnant women and nonpregnant women are essentially the same. UTIs are relatively common in women 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 do have a UTI, they have a higher risk and number of upper UTIs compared with lower UTIs.

Several physiologic changes occur during pregnancy that cause otherwise healthy women to be more susceptible to serious sequelae from the UTIs. The infections can be symptomatic or asymptomatic. Asymptomatic bacteriuria, as the name implies, is UTI without specific symptoms.

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. Urinary stasis and the presence of vesicoureteral reflux predispose some women to upper UTIs and acute pyelonephritis.

Asymptomatic bacteriuria is a risk factor for an upper UTI; treatment of this condition reduces the risk of a symptomatic infection.

Frequency

United States

The frequency of asymptomatic bacteriuria is 2-7%. Several factors are associated with an increased frequency in various patient populations. The most significant factor appears to be socioeconomic status. Indigent patients have a 5-fold increased incidence of bacteriuria compared with that of nonindigent patients. The risk is doubled in women with the sickle cell trait. Other risk factors for bacteriuria include diabetes mellitus, neurogenic bladder retention, and a history of previous UTIs.

Mortality/Morbidity

• Untreated upper UTIs have been associated with a low birth weight, prematurity, premature labor, hypertension and/or preeclampsia, maternal anemia, and amnionitis.
• The literature has reports of the progression of lower UTIs to pyelonephritis in pregnant patients, with rates as high as 40%.

Race

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

Sex

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) bacteria enter the bladder during intercourse.

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

History

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

• Some women with bacteriuria have no symptoms. Usually, bacteriuria is found incidentally and occurs in 2-7% of all pregnant women.
• Burning with urination 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 fetus.
• Pyelonephritis may be present.
• • Fever (Often, the temperature is very high.)
  • Chills
  • Nausea and vomiting
  • Costovertebral angle (CVA) or flank tenderness

Physical

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

• CVA tenderness may be present.
• Suprapubic pain 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 80% of cases)
• Klebsiella species
• Proteus species
• Enterobacter species

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Other Problems to be Considered

Pyelonephritis

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Lab Studies

• In all pregnant patients, a urine specimen should be carefully collected for urinalysis, and potentially, for culturing.
• • These tests help to identify patients with asymptomatic bacteriuria, as well as those with other specific complaints.
  • Bacteriuria generally results in more than 100,000 colonies per milliliter. Counts of less than 100,000 organisms per milliliter per specimen, with 2 or more organisms, usually indicate a contamination rather than an infection.
  • 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.
  • 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 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 and/or infection or in cases of suspected urolithiasis, renal ultrasonography may be helpful.

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

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 UTI and its associated sequelae. 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

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Antibiotic therapy should be initiated after all necessary culture results 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.

Drug Category: 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.

Drug Name	Nitrofurantoin (Macrobid, Furadantin)
Description	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 Dose	ASB or cystitis: 100 mg PO q6h for 10 d Recurrent infections: 100 mg PO q6h for 21 d
Pediatric Dose	5-7 mg/kg/d PO divided q6h
Contraindications	Documented hypersensitivity; renal insufficiency (<60 mL/min CrCl); anuria; oliguria
Interactions	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
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

Drug Name	Trimethoprim and sulfamethoxazole (Bactrim, Septra)
Description	Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Antibacterial activity of TMP-SMZ includes common urinary tract pathogens, except Pseudomonas aeruginosa.
Adult Dose	ASB or cystitis: 160/800 mg PO q12h for 10 d Pyelonephritis: 160/800 mg PO q12h
Pediatric Dose	<2 months: Do not administer >2 months: 15-20 mg/kg/d, based on TMP dose, PO tid/qid for 14 d
Contraindications	Documented hypersensitivity; megaloblastic anemia due to folate deficiency
Interactions	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
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studies 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

Drug Name	Cephalexin (Keflex)
Description	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 Dose	ASB: 250 mg PO q6h for 3 d Cystitis: 250-500 mg PO q6h for 10 d
Pediatric Dose	25-50 mg/kg/d PO q6h; not to exceed 3 g/d
Contraindications	Documented hypersensitivity
Interactions	Coadministration with aminoglycosides increase nephrotoxic potential
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

Drug Name	Ceftriaxone (Rocephin)
Description	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 Dose	Acute pyelonephritis: 1-2 g IV q24h
Pediatric Dose	50-75 mg/kg/d IV divided q12h; not to exceed 2 g/d
Contraindications	Documented hypersensitivity
Interactions	Probenecid may increase levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity
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

Drug Name	Cefazolin (Ancef)
Description	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 Dose	1-2 g IV/IM q8h
Pediatric Dose	25-100 mg/kg/d IV/IM divided q6-8h depending on the severity of the infection; not to exceed 6 g/d
Contraindications	Documented hypersensitivity
Interactions	Probenecid prolongs effect; coadministration with aminoglycosides may increase renal toxicity; may cause false-positive results at urine dip testing for glucose
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

Drug Name	Cefuroxime (Ceftin)
Description	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 Dose	Acute pyelonephritis: 750-1500 mg IV/IM q8h 250-500 mg PO bid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Disulfiramlike 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
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studies 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

Drug Name	Ceftibuten (Cedax)
Description	By binding to one or more of the penicillin binding proteins, arrests bacterial cell wall synthesis and inhibits bacterial growth.
Adult Dose	400 mg PO qd
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Probenecid may increase levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity
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 and allergy to penicillin

FOLLOW-UP

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

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.
• 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. 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
  • Septicemic shock (fairly uncommon)
  • 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.)

Prognosis

• The prognosis is good with appropriate therapy.

Patient Education

• For excellent patient education resources, visit eMedicine's Pregnancy and Reproduction Center and Kidneys and Urinary System Center. Also, see eMedicine's patient education articles Pregnancy and Urinary Tract Infections.

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

• American Academy of Pediatrics and American College of Obstetricians and Gynecology. Guidelines for Perinatal Care. American Academy of Pediatrics. 5^th ed. 2001.
• Gilstrap LC, Ramin SM. Urinary tract infections during pregnancy. Obstet Gynecol Clin North Am. Sep 2001;28(3):581-91. [Medline].
• 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].
• Lucas MJ, Cunningham FG. Urinary infection in pregnancy. Clin Obstet Gynecol. Dec 1993;36(4):855-68. [Medline].
• Lucas MJ, Cunningham FG. Urinary tract infections complicating pregnancy. In: William's Obstetrics. 19^th ed. 1994:1-15.
• 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].
• Miller JM, Raimer KA. Urinary tract infection and pyelonephritis in pregnancy. In: Obstetrics and Gynecologic Infectious Disease. 1994:283-93.
• Schieve LA, Handler A, Hershow R, et al. Urinary tract infection during pregnancy: its association with maternal morbidity and perinatal outcome. Am J Public Health. Mar 1994;84(3):405-10. [Medline].
• Sweet RL, Gibbs RS. Urinary tract infection. In: Infectious Disease of the Female Genital Tract. 3^rd ed. 1995:429-64.
• 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].

Article Last Updated: Aug 8, 2007