Urinary Tract Infection in Women - Jeanne S. Sheffield, MD, and F. Gary Cunningham, MD

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Urinary Tract Infection in Women - Jeanne S. Sheffield, MD, and F. Gary Cunningham, MD
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Urinary Tract Infection in Women
Jeanne S. Sheffield,            MD,   and F. Gary Cunningham,                    MD

               Urinary tract bacterial infections are common in women. Moreover, they tend to recur
               throughout life and in the same relatively small group of women. In most cases, bladder and
               renal infections are asymptomatic and manifest by demonstrating coincidental bacteriuria. In
               some instances, however, especially with frequent sexual activity, pregnancy, stone disease, or
               diabetes, symptomatic cystitis or pyelonephritis develops and antimicrobial therapy is indicated.
               In most cases, cystitis is easily managed with minimal morbidity. When acute pyelonephritis
               develops in an otherwise healthy woman, however, consideration for ureteral obstruction is
               entertained. If her clinical response to proper therapy is not optimal, then imaging studies are
               indicated. Pregnancy is a common cause of obstructive uropathy, and severe renal infections are
               relatively common. Because they usually arise from preexisting covert bacteriuria, experts
               recommend screening and eradication of these silent infections as a routine prenatal practice.
               (Obstet Gynecol 2005;106:1085–92)

U     rinary tract infections are among the most com-
      mon bacterial infections in women. Every year
in the United States, about 10% of women are diag-
                                                                                 uria. Although cystitis is usually uncomplicated, the
                                                                                 upper urinary tract may become involved by ascend-
                                                                                 ing infection. Pyelonephritis is defined as infection of
nosed with cystitis, and this is associated with direct                          the renal parenchyma and pelvicaliceal system, and it
costs of $1.6 billion dollars.1 During their lifetime,                           arises either de novo from asymptomatic renal bacte-
more than half of women will have a urinary infec-                               riuria or from ascending bladder infection. Renal
tion, and up to 50% of these have another infection                              infections are more common in the setting of obstruc-
within a year.2 In approximately 3–5% of women,                                  tion from urinary tract malformations, urolithiasis,
there are multiple recurrences over many years.3                                 and pregnancy-induced changes. Recurrent and
Importantly, urinary infections complicate up to 20%                             chronic infections with the same organism are usually
of pregnancies and are responsible for 10% of all                                termed relapses or persistent infections. If infection
antepartum admissions.4                                                          develops after a symptomatic cure, or if it is caused by
     In most women, these infections are limited to the                          a second pathogen, it is termed a reinfection. Acute
lower urinary tract and are manifest by asymptomatic                             urethritis, caused predominantly by Neisseria gonor-
bacteriuria. Cystitis is the most common symptomatic                             rhoeae and Chlamydia trachomatis usually occurs con-
                                                                                 comitant with cervicitis. Management of these sexu-
infection and is characterized by dysuria, urgency,
                                                                                 ally transmitted diseases is detailed elsewhere.5
and frequency concomitant with pyuria and bacteri-

From the Department of Obstetrics & Gynecology, University of Texas South-
                                                                                 PATHOPHYSIOLOGY
western Medical Center, Dallas, Texas.                                           Urinary infection in women results from complex
Corresponding author: Jeanne S. Sheffield, MD, Assistant Professor, Department   interactions between host and microorganism. Most
of Obstetrics & Gynecology, 5323 Harry Hines Boulevard, University of Texas      commonly, infection arises from perineal and periure-
Southwestern Medical Center, Dallas, TX 75390-9032; e-mail:
Jeanne.Sheffield@utsouthwestern.edu.
                                                                                 thral bacteria that gain entrance to the bladder. Such
© 2005 by The American College of Obstetricians and Gynecologists. Published
                                                                                 extension of colonization or infection most probably
by Lippincott Williams & Wilkins.                                                is associated with physiological trauma such as sexual
ISSN: 0029-7844/05                                                               intercourse. It may also follow urethral massage or

VOL. 106, NO. 5, PART 1, NOVEMBER 2005                                                             OBSTETRICS & GYNECOLOGY          1085
Urinary Tract Infection in Women - Jeanne S. Sheffield, MD, and F. Gary Cunningham, MD
catheterization. Ascending infection may then involve             also at increased risk, presumably secondary to
the ureters, pyelocaliceal system, and renal paren-               changes in the vaginal flora and possibly trauma from
chyma (Fig. 1). Rarely, renal infection may result                the diaphragmatic ring. An increased risk of infection
from bacteremia or lymphatic spread.                              accrues with age, likely due to the hypoestrogenic
                                                                  state with vaginal mucosal atrophy, impaired voiding,
Host Factors                                                      and changes in hygiene. There are other risk factors,
Women are anatomically predisposed to bacterial                   including medical conditions such as diabetes, obe-
colonization. The external third of the short urethra             sity, and sickle cell trait; anatomical congenital abnor-
often is colonized by pathogens from normal vagina                malities; urinary tract calculi; and neurological or
flora. Intercourse increases the risk of infection due to         anatomical disorders that require indwelling or repet-
meatal trauma, urethral massage, and probably,                    itive bladder catheterization.
changes in vaginal flora. Women who use a dia-                         One of the most important risk factors for symp-
phragm with spermicidal agents for contraception are              tomatic infection, especially acute pyelonephritis, is
                                                                  pregnancy-induced physiological changes in the uri-
                                                                  nary system. Dilation of the ureters and renal calyces
                                                                  is evident as early as 12 weeks and is thought to be
                                                                  caused by progesterone-induced relaxation of their
                                                                  muscular layers. More importantly, as the uterus
                                                                  enlarges, it begins to compress the ureters at the
                                                                  pelvic brim, particularly on the right.6,7 Vesicoureteral
                                                                  reflux may first appear or worsen during gestation in
                                                                  some women, particularly multiparas. Anatomical
                                                                  changes in bladder position in late pregnancy also
                                                                  may render it more susceptible to infection. Finally,
                                                                  bladder and urethral trauma, periurethral tears, large
                                                                  vulvar lacerations, and epidural analgesia for labor
                                                                  and delivery predispose to urinary retention and the
                                                                  need for catheterization.

                                                                  Bacterial Factors
                                                                  Urinary infections in women are caused by a number
                                                                  of bacterial species, the majority of which are from
                                                                  normal perineal flora. Specific serogroups of “uro-
                                                                  pathogenic” Escherichia coli are the most commonly
                                                                  identified organisms.8 These serogroups have a num-
                                                                  ber of virulence factors specific for colonization and
                                                                  invasion of urinary epithelium. Some of these include
                                                                  adhesins, such as P-fimbria and S-fimbria, which
                                                                  enhance binding to vaginal and uroepithelial cells
                                                                  (Fig. 2). These adhesins also bind to erythrocyte
                                                                  membranes and inhibit serum bactericidal activity by
                                                                  expression of the dra gene cluster associated with
                                                                  ampicillin resistance.9 Other E coli serogroups express
                                                                  an increase in K antigen production which helps
                                                                  protect the microorganism from leukocyte phagocy-
                                                                  tosis. Greater adherence of type I fimbriated E coli to
Fig. 1. Routes of infection in the urinary tract. Arrows depict   uroepithelial cells in diabetes may be related to
the ascending nature of infection, from the bladder and           impaired cytokine secretion and blunted leukocyte
urethra up the ureters to the kidneys. Modified from Amer-        response.10 A complete list of identifiable virulence
ican College of Obstetricians and Gynecologists. Urogyne-
                                                                  factors is beyond the scope of this review.
cology: an illustrated guide for women. Washington, DC:
ACOG; 2004. Illustration: John Yanson.                                 Although the overwhelming majority of urinary
Sheffield. Urinary Tract Infection in Women. Obstet Gynecol       infections are caused by strains of E coli, most of the
2005.                                                             remainder are caused by Enterobacter, Enterococcus,

1086   Sheffield and Cunningham         Urinary Tract Infection in Women                   OBSTETRICS & GYNECOLOGY
pregnant women is usually not recommended. More-
                                                                over, there is little evidence that treatment alters the
                                                                overall natural history of silent infection. One excep-
                                                                tion recommended by The American College of
                                                                Obstetricians and Gynecologists (ACOG) in 2003 is
                                                                the diabetic woman. During pregnancy asymptomatic
                                                                bacteriuria screening and treatment is also recom-
                                                                mended. Depending on the population, the incidence
                                                                of asymptomatic bacteriuria during pregnancy ranges
                                                                from 2% to 7%. Bacteriuria is typically present at the
                                                                time of the first prenatal visit, and after an initial negative
                                                                urine culture, less than 1% of women develop acute
                                                                cystitis.16 If asymptomatic bacteriuria is not treated, a
Fig. 2. Transmission electron microscopy showing fimbri-        fourth of these women subsequently develop acute
ated Escherichia coli adhering to a transitional cell           pyelonephritis. Thus, ACOG17 recommends routine
(⫻ 180,000, original magnification). Arrows show the pili.      screening for bacteriuria at the first prenatal visit, with
Modified from Roberts JA. Pathophysiology of pyelonephri-       eradication to prevent serious renal infections during
tis. Infect Surg 1986;Nov:633.                                  pregnancy. There is little evidence that asymptomatic
Sheffield. Urinary Tract Infection in Women. Obstet Gynecol
2005.
                                                                bacteriuria has a significant clinical impact on other
                                                                significant adverse pregnancy outcomes.18
                                                                     Treatment for asymptomatic bacteriuria is usually
Proteus mirabilis, and Klebsiella species. These latter         empirical, and determination of in vitro susceptibili-
organisms also are associated with structural abnor-            ties is not necessary. A number of antimicrobial
malities or renal calculi. Staphylococcus saprophyticus has     regimens have proven effective. These are listed in
been isolated from 3% of nonpregnant reproductive-              Table 1 with their relative costs. Although it is doubt-
age women with pyelonephritis.11 Gram-positive or-              ful that 3-day exposures are harmful to the fetus, some
ganisms, including group B Streptococcus, are increas-          recommend against the use of fluoroquinolone deriv-
ingly isolated in certain populations, including                atives as first-line treatment because animal and hu-
pregnant women.12 Patients with indwelling catheters            man toxicity data interpretation has been controversial.
are also susceptible to fungal infections. Finally anaer-       For resistant infection, however, use of these drugs is
obic bacteria and mycoplasmas may play a greater                certainly reasonable. We have found that nitrofurantoin
role in urinary infections than previously reported,            macrocrystals, 100 mg at bedtime for 10 days, is effec-
although data are limited.                                      tive and has a high compliance rate. Regardless of the
                                                                regimen chosen, recurrent asymptomatic bacteriuria is
LOWER URINARY TRACT INFECTIONS                                  identified in at least 30% of women.16 At this point,
Asymptomatic Bacteriuria                                        another regimen from Table 1 is given.
The prevalence of bacteriuria in sexually active
young women is reported to be as high as 5– 6%.13               Acute Cystitis
This prevalence is similar during pregnancy and most            Acute bladder infection is often uncomplicated and
women are asymptomatic. Bacteriuria is diagnosed by             accompanied by varying degrees of dysuria, fre-
using a clean-voided, midstream urine sample. For               quency, and urgency. Patients may also complain of
research purposes, significant bacteriuria is defined as        suprapubic pain and fullness. Although acute cystitis
isolation of a single microorganism with at least               may irritate the lower uterine segment and incite
100,000 organisms/mL (colony forming units or cfu/              preterm contractions, there is no evidence that it
mL). Although some authors recommend using a                    causes preterm labor. Diagnosis is based on these
colony count of 10,000/mL or greater to increase the            clinical findings and confirmed by urine studies.
sensitivity of the test. However, most use 100,000              Urinary dipstick testing is fast and convenient. A
cfu/mL or greater to be clinically significant and thus         finding of either nitrite or leukocyte esterase is con-
require treatment.14,15                                         sidered a positive result, with a sensitivity of 75% and
                                                                specificity of 82%.2,19,20 Urine culture is indicated in a
Treatment                                                       symptomatic woman not responding to standard ther-
Because of its propensity for almost inevitable recur-          apy who occasionally may have a resistant pathogen.
rence, treatment of asymptomatic bacteriuria in non-            The distal urethra and periurethral colonized areas

VOL. 106, NO. 5, PART 1, NOVEMBER 2005               Sheffield and Cunningham     Urinary Tract Infection in Women        1087
Table 1. Treatment Regimens for Uncomplicated                     Recurrent Cystitis
         Urinary Infections in Women and the                      Recurrent urinary infections, both symptomatic and
         Relative Cost of Each Regimen*                           asymptomatic, are common in women, occurring in
Treatment Regimen                                        Cost     up to 35%. During pregnancy at least, a “test of cure”
Single-dose treatment                                             urine culture is performed 1–2 weeks after completing
   Ampicillin, 2 g                                     $          therapy and a different treatment regimen used, if
   Amoxicillin, 3 g                                    $          positive. Imaging studies are rarely indicated. Women
   Nitrofurantoin, 200 mg                              $          who have 3 or more symptomatic infections over a
   Trimethoprim-sulfamethoxazole, 320/1,600 mg          $
                                                                  12-month period may benefit from continuous pro-
3-Day course
   Amoxicillin, 500 mg 3 times daily                   $          phylaxis. Antibiotics, including nitrofurantoin, cipro-
   Ampicillin, 250 mg 4 times daily                    $          floxacin, trimethoprim, or norfloxacin, have all been
   Cephalexin, 250 mg 4 times daily                   $$$         shown to decrease the recurrence risk by 95% or more
   Nitrofurantoin, 50 mg 4 times daily; 100 mg                    when used in a prophylactic regimen.2 Postcoital pro-
   twice daily                                         $$
                                                                  phylaxis is another option available.
   Trimethoprim-sulfamethoxazole, 160/800 mg
   twice daily                                         $$              Cranberry or lingonberry juice has been shown
   Ciprofloxacin, 250 mg twice daily                  $$$         in randomized trials to decrease the risk of recurrent
   Levofloxacin, 250 mg daily                         $$$         urinary infections. This is due to the proanthocyani-
Other                                                             dins inhibiting attachment of urinary pathogens to the
   Nitrofurantoin, 100 mg at bedtime for 7–14 days    $$$
                                                                  epithelium.2 Doses of 200 –750 mL or equivalent
   Nitrofurantoin, 100 mg 4 times daily for 7–14 days $$$$
Treatment failures                                                concentrated tablets daily have been found effective.
   Nitrofurantoin, 100 mg at bedtime for 21 days      $$$$        Other proposed preventive measures, such as wiping
Suppression for bacterial persistence or recurrence               techniques, postcoital voiding, douching, and timing
   Nitrofurantoin, 100 mg at bedtime for remainder of             of voiding, have not been shown to prevent recurrent
   pregnancy                                          N/A
                                                                  infections.2
$ ⱕ $5; $$ ⬎ $5 ⱕ $15; $$$ ⬎ $15 ⱕ $30; $$$$ ⬎ $30.
* Based on generic average wholesale price (Redbook Pharmacy’s
   Fundamental Reference37) per regimen when available.           ACUTE PYELONEPHRITIS
Modified from Cunningham FG, Leveno KJ, Bloom SL, Hauth JC,
   Gilstrap LC, Wenstrom KD. Renal and urinary tract disorders.
                                                                  Nonpregnant Women
   In: Cunningham FG, Leveno KJ, Bloom SL, Hauth JC, Gilstrap     Acute pyelonephritis is a clinical syndrome character-
   LC, Wenstrom KD, editors. Williams obstetrics, 22nd ed. New    ized by flank pain, chills and fever, and variable
   York (NY): McGraw-Hill; 2005. p.1095-9. Reproduced with
   permission of The McGraw-Hill Companies.                       symptoms of dysuria, urgency, and frequency. The
                                                                  diagnosis is verified by demonstrating significant bac-
                                                                  teriuria. As discussed, despite its high prevalence,
may contaminate a midstream clean-voided urine                    asymptomatic bacteriuria in nonpregnant women
specimen but with lower colony counts. A urine                    rarely develops into pyelonephritis, except in diabetic
culture should be obtained by catheterization in prob-            women. For nondiabetic women who develop pyelo-
lematic cases. Some cases of persistent lower-tract               nephritis, urinary tract abnormalities, urolithiasis, and
symptoms may be due to epithelial infection with                  other obstructive causes must be considered. By far,
Chlamydia trachomatis.5                                           the most common risk factor for acute pyelonephritis
                                                                  is pregnancy.
Treatment
In most cases, uncomplicated bacterial cystitis re-               Treatment
sponds quickly to single-dose or 3-day therapy. The               Unless there are overt complications, therapy for
3-day regimens shown in Table 1 are effective in at               women with acute uncomplicated pyelonephritis is
least 90% of women.2 Recently, it has been recom-                 usually given as an outpatient. For women who have
mended that ␤-lactams alone not be used to treat                  overt sepsis or those who are unable to tolerate oral
urinary infections because of increasing resistance               antimicrobial agents or fluids, hospitalization and
among the common uropathogens.2                                   parenteral antibiotics are recommended. The woman
     In pregnant women with cystitis, single-dose ther-           should be given appropriate intravenous hydration,
apy is not recommended. Any of the 3-day treatment                and unless previous antimicrobial sensitivity data are
regimens shown in Table 1 are effective, with the                 available, antibiotic therapy is empirical. Table 2 lists
same caveats for fluoroquinolone derivatives as dis-              common regimens used for the treatment of uncompli-
cussed for asymptomatic bacteriuria above.                        cated pyelonephritis. Their relative costs are also listed.

1088   Sheffield and Cunningham         Urinary Tract Infection in Women                    OBSTETRICS & GYNECOLOGY
Table 2. Intravenous and Oral Regimens for the                       intravenous pyelography is used to identify an obstruct-
         Treatment of Acute Uncomplicated                            ing stone.22 The renal parenchyma is also visualized with
         Pyelonephritis and the Relative Cost per                    sonography, and pyelonephritis usually causes some
         Day of Each Regimen*                                        renal enlargement. Intra- or perirenal abnormalities are
Regimen                                                     Cost     better assessed with contrast-enhanced computed to-
Outpatient regimens (10–14 days)                                     mography. Parenchymal abnormalities appearing as an
   Ciprofloxacin, 500 mg twice daily                          $      area of sharply demarcated attenuation signifies an
   Ciprofloxacin-XR, 1,000 mg once daily                      $      intrarenal phlegmon, also termed lobar nephronia or focal
   Gatifloxacin, 400 mg once daily                            $      or segmental pyelonephritis (Fig. 3). These areas some-
   Levofloxacin, 250 mg once daily                            $      times suppurate and drainage may be necessary. In
   Ofloxacin, 400 mg twice daily                              $
   Amoxicillin-clavulanate, 875/125 mg twice daily            $      either case, there is a prolonged hospital course. Finally,
   Trimethoprim-sulfamethoxazole DS, 160/800                         some women will be found to have a perinephric
      mg twice daily                                          $      phlegmon or abscess. The latter is quite serious and
Intravenous regimens                                                 drainage is frequently necessary.
   Ciprofloxacin, 400 mg every 12 hours                      $$$
   Levofloxacin, 500 mg once daily                           $$
                                                                     Pregnancy
   Cefepime, 2 g every 8 hours                              $$$$
   Cefotetan, 2 g every 12 hours                            $$$      Acute pyelonephritis is the most common serious
   Ticarcillin-clavulanate, 3.1 g every 6 hours             $$$      medical complication of pregnancy.4 From most sur-
   Trimethoprim-sulfamethoxazole, 2 mg/kg                            veys, 1–2% of pregnant women are admitted for this
      every 6 hours                                          $$      condition despite prenatal screening and treatment
   Ceftriaxone, 1–2 g every 12–24 hours                     $$$$
   Gentamicin, 3–5 mg/kg per day (once daily dosing                  for bacteriuria. Renal infections may result in signifi-
      acceptable)                                             $      cant maternal morbidity and occasional mortality. At
   Ampicillin, 2 g every 6 hours – for suspected                     our institution, 12% of antepartum admissions to the
      enterococcus                                           $$      obstetric intensive care unit are for sepsis caused by
   Aztreonam, 2 g every 8 hours                             $$$$     pyelonephritis.24 Acute renal infection is less common
   Cefotaxime, 1–2 g every 8 hours                          $$$
                                                                     in early pregnancy, except in diabetic women. As
$ ⱕ $20; $$ ⬎ $20 ⱕ $60; $$$ ⬎ $60 ⱕ $100; $$$$ ⬎ $100.              many as 80 –90% of cases are reported to occur either
* Based on generic average wholesale price per day when available.
                                                                     in the latter 2 trimesters or in the puerperium.12 This
                                                                     observation is related to the increasing urinary tract

     After urine is obtained for culture, one of the
regimens listed in Table 2 should be started. These
febrile women usually are quite dehydrated; there-
fore, they should receive intravenous crystalloid solu-
tions as well as a dose of parenteral antimicrobials
before discharge if outpatient management is
planned. In a recent study of 242 nonpregnant
women aged 18 – 49 years with acute pyelonephritis,
Scholes et al11 reported that only 7% required hospi-
talization. When patients are admitted, any of the
intravenous agents listed in Table 2 can be given.
When the organism susceptibility data becomes avail-
able, therapy is altered as needed. A 10-day course of
treatment is recommended.2,21
     Clinical response should occur within 48 –72
hours of starting therapy. If no improvement is noted
or if the patient status worsens, aggressive investiga-
tion for complications of renal infection or urinary
obstruction should be undertaken. Renal ultrasonog-
                                                                     Fig. 3. Abdominal computed-tomographic scan with contrast
raphy is the best noninvasive method to evaluate for
                                                                     depicting lobar nephronia. The wedge-shaped nonenhanced
obstruction within the renal collecting system. The                  area within the left kidney is indicated by arrowheads.
most common cause of obstruction is stones. In many                  Sheffield. Urinary Tract Infection in Women. Obstet Gynecol
cases, calculi are not seen with ultrasonography, and                2005.

VOL. 106, NO. 5, PART 1, NOVEMBER 2005                 Sheffield and Cunningham        Urinary Tract Infection in Women        1089
obstruction with stasis caused by progesterone and
uterine enlargement.
      Clinical findings are similar to those for nonpreg-
nant women. In over half of cases, pyelonephritis is
unilateral and right-sided, and it is left-sided or bilat-
eral in another 25% each. The right-sided predomi-
nance may be from obstruction due to uterine dex-
trorotation, protection from obstruction provided on
the left by the descending colon, or both. Onset of
illness usually is abrupt, with fever, chills, and aching
pain in one or both lumbar regions. There frequently
is anorexia, nausea, and vomiting, which worsen
dehydration resulting from fever. Tenderness usually
can be elicited by percussion in one or both costover-
tebral angles, and urinalysis discloses bacteriuria that
is confirmed by culture. As many as 20% of these
women will have bacteremia. E coli is by far the most
common pathogen identified, but gram-positive or-
ganisms, including group B Streptococcus, account for
about 10% of cases of acute pyelonephritis at our
institution.12
      About 1 in 5 pregnant women with pyelonephri-          Fig. 4. Pregnant woman at 28 weeks of gestation admitted
                                                             for severe pyelonephritis, sepsis syndrome, and preterm
tis will develop evidence of multiple-system derange-        labor. Within 24 hours of delivering a liveborn infant, she
ment from endotoxemia and sepsis syndrome.12,19,25–29        developed purpura fulminans and was transferred to the
These disorders result from endothelial activation that      burn intensive care unit. She sloughed 90% of her skin and
is followed by capillary fluid extravasation with dimin-     died from dermal septicemia.
ished perfusion. These vascular changes aggravate the        Sheffield. Urinary Tract Infection in Women. Obstet Gynecol 2005.
dehydration from nausea, vomiting, and fever, and
resultant hypotension is common. Fortunately, most           worst form, pulmonary injury causes severe acute
women respond to rapid fluid resuscitation with intra-       respiratory distress syndrome as shown in Figure 5.
venous crystalloid solutions, and cardiac output is re-      Most women with pulmonary capillary injury will
stored without the use of vasopressor drugs.
      There are a number of sepsis-related derange-
ments that are commonly reported. With early and
aggressive fluid resuscitation, only about 5% of
women have seriously diminished renal function.12
Before the concept of aggressive hydration, however,
this number was 20%.25,26 Although transient, renal
dysfunction is important to recognize so that nephro-
toxic drugs can be avoided. Anemia is common, and
up to a fourth of women have a hematocrit drop to
less than 30 volumes percent. In severe cases, the
hematocrit falls as low as 20 volumes percent. Hemo-
lysis is caused by the lipopolysaccharide in endotoxin
and is associated with deranged erythrocyte morphol-
ogy and elevated serum L-lactate dehydrogenase lev-
els.27 With severe sepsis, activation of coagulation is
common with potentially serious complications (Fig. 4).
      The most common serious manifestation of sepsis
                                                             Fig. 5. A semi-upright anteroposterior chest radiograph
syndrome is acute respiratory insufficiency, which           demonstrating diffuse bilateral parenchymal infiltrates and
develops to varied degrees in up to 10% of pregnant          pleural effusions consistent with acute respiratory distress
women.12 Endotoxin injures endothelium and alters            syndrome (courtesy of Dr. Diane Twickler).
alveolar capillary membrane permeability. In its             Sheffield. Urinary Tract Infection in Women. Obstet Gynecol 2005.

1090   Sheffield and Cunningham      Urinary Tract Infection in Women                     OBSTETRICS & GYNECOLOGY
respond to increased oxygen delivered by face mask                          itoring with pulse oximetry should be performed. The
and a 10- to 20-mg dose of furosemide given intrave-                        diagnosis of pyelonephritis is confirmed promptly
nously. In severe cases, intubation and mechanical                          and intravenous antimicrobials are begun. Blood cul-
ventilation may be lifesaving. Some women require                           tures have been shown to have limited utility in
100% oxygen by nonrebreathing mask or by nasal                              management.33 Urinary output, blood pressure, and
continuous positive airway pressure. In some of these                       temperature are monitored closely. High fever can be
women, tracheal intubation and mechanical ventila-                          lowered with a cooling blanket or acetaminophen.
tion is necessary to maintain oxygenation.28                                This is especially important in early pregnancy be-
     Uterine activity stimulated by endotoxin is com-                       cause of possible teratogenic effects of hyperthermia.
monly seen. Millar et al30 reported that women had an                            Outpatient management of pyelonephritis in
average of 5.1 contractions per hour when admitted                          pregnancy is an option in those women able to
for pyelonephritis. This number decreased to 2.0 per
                                                                            tolerate oral intake with no evidence of sepsis, serious
hour by 6 hours. Even so, preterm labor is not
                                                                            underlying medical illness, respiratory insufficiency,
common. When it is identified, care must be taken
                                                                            known renal or urologic disorders, or preterm la-
with tocolysis. ␤-agonist therapy increases the likeli-
                                                                            bor.34,35 Table 2 lists common outpatient regimens
hood of respiratory insufficiency from alveolar flood-
ing because of its sodium and fluid retaining proper-                       available.
ties.31 In the study by Towers et al,32 the incidence of                         A number of antimicrobial regimens that may be
pulmonary edema was 8% in women with pyelone-                               used are detailed in Table 2. We initially give ampi-
phritis who were given ␤-agonists. Because of this,                         cillin plus gentamicin. In general, women will re-
magnesium sulfate is often used preferentially.                             spond to therapy within 48 hours. For nonresponders,
                                                                            a search for obstruction or complicated infections is
                                                                            done as outlined above for nonpregnant women.
Treatment
                                                                            Once afebrile, women can be discharged to complete
Pregnant women with acute antepartum pyelonephri-
                                                                            a 10-day course of therapy.
tis should initially be assessed in the hospital (see box,
                                                                                 Recurrent bacteriuria develops in 30 – 40% of
‘‘Management of the Hospitalized Pregnant Women
                                                                            women after completion of therapy, and if untreated,
With Acute Pyelonephritis’’). During this time, hydra-
                                                                            one fourth develop recurrent pyelonephritis.29 We
tion is paramount while laboratory studies and further
clinical evaluation are done. Women who cannot                              recommend nitrofurantoin suppression, 100 mg at
tolerate oral medications are hospitalized as are                           bedtime, for the remainder of pregnancy to reduce
women who appear very ill. Vigorous crystalloid                             the likelihood of recurrent infection.36 In our hospital,
infusion to ensure adequate urinary output is a main-                       3% of women develop recurrent pyelonephritis during
stay of treatment. Because pulmonary edema is a risk                        the same pregnancy, and in almost every case, they
of aggressive hydration in these women, careful mon-                        were noncompliant with the suppression regimen.12

 Management of the Hospitalized Pregnant Women With Acute Pyelonephritis
  1.   Hospitalization
  2.   Urine studies
  3.   Hemogram, serum creatinine, and electrolytes
  4.   Monitor vital signs frequently, including urinary output; consider indwelling catheter
  5.   Intravenous crystalloid to establish urinary output 50 mL/hr
  6.   Intravenous antimicrobial therapy
  7.   Chest radiograph if there is dyspnea or tachypnea
  8.   Repeat hematology and chemistry studies at 48 hours if clinically relevant
  9.   Change antimicrobials if necessary when sensitivity results are available
 10.   Discharge when afebrile for 24 hours; administer antimicrobials 10 days total therapy
 11.   Urine studies 1–2 weeks after therapy completed to ‘‘test for cure’’

 Modified from Lucas MJ, Cunningham FG. Urinary tract infections complicating pregnancy. In: Williams obstetrics. 19th ed. (suppl 5). Norwalk (CT):
 Appleton& Lange; 1994. Reproduced with permission of The McGraw-Hill Companies.

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