Current Diagnosis & Treatment in Infectious Diseases

Section II - Clinical Syndromes

22. Obstetric & Gynecologic Infections

Yenjean S. Hwang MD

Merle A. Sande MD

GYNECOLOGIC INFECTIONS

VULVOVAGINITIS

Essentials of Diagnosis

  • Risk factors: use of antibiotics, elevated levels of estrogen, sexually active lifestyle, history of sexually transmitted diseases.
  • Vulvar irritation, dysuria, vaginal discharge with or without odor, labial erythema.
  • Change in vaginal pH.
  • Microscopic examination of vaginal secretions may show characteristic yeast forms, clue cells, or trichomonads.

General Considerations

Vulvovaginitis is an extremely common syndrome; one study found that vulvovaginitis was diagnosed in more than 25% of the women attending sexually transmitted diseases clinics. It is estimated that 75% of all women experience at least one episode of vulvovaginal candidiasis in their lifetime. The organisms that cause vulvovaginitis cause very similar symptoms, so that a specific diagnosis cannot be made on symptoms alone (Table 22-1).

The most common infectious agents that cause vulvovaginitis are Candida albicans and other Candida species, Trichomonas vaginalis (which is discussed in Chapter 15), and agents involved in bacterial vaginosis (BV) (Box 22-1). Other etiologic agents include Staphylococcus aureus, herpes simplex virus (HSV), and papillomavirus. Much rarer agents, seen mainly in immunocompromised patients, include M tuberculosis, Salmonellae, Enterobacteriaceae, actinomycetes, and schistosomes. Noninfectious vaginitis can be caused by a foreign body, a genital neoplasm, estrogen deficiency in postmenopausal women leading to atrophic vaginitis, chemical vaginitis, and allergic reactions. Lichen planus can cause desquamative vaginitis, and fixed-drug eruptions can cause lesions in the genital area. This section will focus on candidal vaginitis, trichomonal vaginitis, and BV.

Vulvovaginal candidiasis accounts for approximately one-third of all cases of vulvovaginitis. Candida albicans probably accounts for 80–90% of cases of vulvovaginal candidiasis. Candida tropicalis accounts for 5% and is associated with a higher rate of recurrence after treatment. Torulopsis glabrata accounts for 10%, and this type of vulvovaginal candidiasis may be more difficult to eradicate with standard therapies. The relative incidence of vaginitis caused by fungi other than C albicans appears to be increasing in some populations, which is attributed in part to the common use of topical antifungal agents in short courses. Factors favoring overgrowth of yeasts include the use of antibiotics, presence of high estrogen levels as in pregnancy and during oral-contraceptive use, wearing of tight clothing, and impairment of cell-mediated immunity or phagocytic cell function (as often occurs in women with AIDS or during post-transplant or post-chemotherapy periods).

BV is a polymicrobial infection associated with Gardnerella vaginalis, a gram-variable pleomorphic rod. This condition is more frequent in sexually active women and in populations with a higher prevalence of sexually transmitted diseases. The pathophysiology of BV is unclear, but a loss of the normal predominance of Lactobacillus species and increases in vaginal pH and numbers of anaerobic and aerobic bacteria are suspected. The characteristic fishy odor of BV may be caused by increased numbers of such anaerobes as Bacteroides, Prevotella, Peptostreptococcus, and Mobiluncus species and genital mycoplasmas. There is evidence to support the idea that BV is a sexually transmitted disease, in that G vaginalis can be isolated from the urethras of more than 80% of the male sexual partners of women with BV. However, G vaginalis can also be isolated from prepubescent girls who are not sexually active and from sexually inactive women. BV can be seen in women or girls who have never been sexually active, and the disease can recur even without sexual reexposure. BV tends to occur in women older than those who are at risk for gonorrhea and chlamydia. Women who are diagnosed as having BV should be screened for other sexually transmitted diseases, but it is not currently recommended that their sexual partners be routinely treated as well.

Table 22-1. Typical features of common vaginitides.1

 

Candida

Trichomonas

Bacterial Vaginosis

Vulvar irritation

++

++

- to +

Dysuria

+

20%

-

Labial erythema

- to +

- to +

-

Satellite lesions

+

-

-

Consistency of discharge

Curdy

Frothy 25%

Homogenous, frothy sometimes

Color of discharge

White

Yellow-green, 25%

Gray, white

Vaginal pH

≤4.5

≥4.7

≥4.7

Epithelial cells

Normal

Normal

Clue cells

PMNs per epithelial cells

Variable

>1

<1

Bacteria

Endogenous flora

Endogenous flora

Gram-variable coccobacilli

Pathogens on microscopy

Yeasts and pseudohyphae, 50%

Trichomonads 70%

Gram-variable coccobacilli

1Source: Adapted from Rein MF: Vulvovaginitis and cervicitis. In Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Churchill Livingstone, 1995.

BOX 22-1 Microbilogy of Vulvovaginitis

 

Children

Adults

More Frequent

· Gardnerella vaginialis

· Group A streptococci

· Candida albicans

· Candida

· Trichomonas vaginalis

· Bacterial vaginosis (Gardnerella vaginalis)

Less Frequent

· Haemophilus influenzae

· Enterobius vermicularis

· Staphylococcus aureus

· Herpes simplex virus

· Human papillomavirus

· Mycobacterium tuberculosis

· Salmonellae

· Enterobacteri-aceae

· Actinomyces

· Schistosomes

 

Clinical Findings (see Table 22-1, “Typical Features of Common Vaginitides”)

  1. Signs and Symptoms.Perivaginal pruritis is frequent with all three types of common infectious vaginitides, ie, candidal, trichomonal, and bacterial agents. Dysuria may be present. In candidal vulvovaginitis, there is often little or no vaginal discharge, but if present, it is usually thick and curdy. The labia may be pale or erythematous; there may also be small satellite papules or papulopustules at the margin of the erythematous area. Trichomonal vaginitis is also associated with vaginal irritation and sometimes dysuria and labial erythema. There may be a frothy greenish discharge. BV can present in the same manner but with a characteristically strong odor to the vaginal discharge, which is also usually gray-white in color. Physical examination may reveal very few abnormal findings, as there is rarely uterine or adnexal tenderness.
  2. Laboratory Findings.The vaginal pH in candidal vaginitis is normal (4.5), whereas in trichomonal vaginitis and BV it is usually elevated. Adding 10% potassium hydroxide to vaginal discharge fails to elicit a fishy odor in candidiasis, whereas trichomonal vaginitis and BV have characteristically fishy odors (positive “whiff” test). Yeast forms may be visible under microscopy on a KOH preparation, although they are not visible in 30–50% of women who have candidal vulvovaginitis. With trichomonal vaginitis, microscopy should reveal trichomonads in 70% of cases. Epithelial cells appear normal, and there may be an increased number of polymorphonuclear cells. On wet mount examination of vaginal discharge in BV, clue cells, which are vaginal epithelial cells studded with tiny coccobacilli, can be seen. Culturing for G vaginaliscan be performed, but the appearance of clue cells on the wet mount appears to be the most specific criterion for the diagnosis of BV.

Differential Diagnosis

As discussed above, other types of vaginal infections and processes can mimic vulvovaginitis caused by Candida, Trichomonas, and Gardnerella species.

Complications

Trichomonal infection can be complicated by vaginitis emphysematosa, in which gas-filled pockets of tissue fill the vaginal wall. This condition will resolve upon treatment of the trichomonal infection. Women with trichomonal vaginitis are more likely to have vaginal-cuff cellulitis after hysterectomy and, if they are pregnant, are more likely to have premature or prolonged rupture of membranes, premature labor, low-birth-weight babies, and postabortion infection. Women with BV are at increased risk for salpingitis, vaginal-cuff and wound infections after surgery, postpartum fever, chorioamnionitis, premature labor, and premature delivery. The treatment of both candidal and trichomonal vaginitis may be complicated by frequent recurrences.

Treatment

Vulvovaginal candidiasis is usually treated with topical antifungal agents (Box 22-2). There are a wide variety of treatments, all of which appear to be equally effective. Commercially available preparations, usually imidazoles or triazoles, are safe in pregnancy and tolerated well by patients. Treatment with an imidazole for 7 days yields a cure rate of approximately 80–94%. Shorter (3-day) regimens have approximately the same cure rate with improved patient compliance. Single-dose regimens do not appear to be as effective as the 3- or 7-day treatments. Pregnant women may require longer treatment. Oral therapy with fluconazole, ketoconazole, and itraconazole is available as well, but the potential toxicities are greater, and most patients do not require systemic therapy. Recurrent infection can be a problem with vulvovaginal candidiasis and probably results from endogenous relapse caused by small numbers of yeasts that have survived treatment. The rate of recurrence may be decreased by administering short courses of topical or oral antifungal agents during days 5–11 of the menstrual cycle, switching to a lower-estrogen-dose formulation of an oral contraceptive, and treating the male partner if he has candidal balanitis.

Trichomonal vaginitis should be treated with metronidazole (see Chapter 15 for more detailed discussion). The sexual partner should be treated simultaneously. Metronidazole is contraindicated in early pregnancy and in lactating women.

BV can be treated with metronidazole. Clindamycin and oral cephalosporins are also acceptable therapy. Vaginal regimens are also available, and cure rates are reported to be similar to those achieved with oral metronidazole.

Prognosis

Topical treatment of candidal vulvovaginitis has a cure rate range of 80–94%. However, 3–6 weeks after completion of treatment, Candida can be cultured from quite a few women (9–33%) who have undergone this treatment. Subspeciation of Candida suggests that approximately 40% of these women are infected with new strains of Candida species. Our current understanding of the mechanism of recurrence is extremely limited. Therapy to decrease the number of recurrences is aimed at eliminating or minimizing the aforementioned risk factors.

In Trichomonas vaginalis infection, a single dose of metronidazole reportedly provides a cure rate of 90%. For BV, cure rates associated with treatment with metronidazole are reported to be 80–90%.

CERVICITIS

Essentials of Diagnosis

  • Risk factors: young (under age 24), unmarried, sexually active women; lower socioeconomic status, a new sexual partner within the past 2 months, a history of gonococcal infection, and a history of T vaginalisinfection; women who use an intrauterine device (IUD) are prone to infection with actinomycetes.
  • Erythema around the cervical os, mucopurulent cervical discharge, fever, chills, and uterine tenderness may be present, or patients may be asymptomatic.
  • Ten to thirty polymorphonuclear leukocytes per oil immersion field on Gram stain of cervical discharge.
  • Ligase chain reaction (LCR) and polymerase chain reaction (PCR) tests for rapid diagnosis of cervicitis caused by Chlamydia trachomatisand Neisseria gonorrhoeae.

General Considerations

Cervicitis is also covered in Chapter 15. The most common causes of cervicitis are N gonorrhoeae and C trachomatis (Box 22-3). Populations at higher risk for cervicitis include young (under age 24), unmarried, sexually active women of lower socioeconomic status. Their risk increases if they have had a new sexual partner in the past 2 months, a history of gonorrhea, or a history of infection with T vaginalis. Asymptomatic or latent infection appears to be common with both organisms, leading to such complications as salpingitis, tubo-ovarian abscess, pelvic inflammatory disease (PID), and potential infertility. Concomitant infection with more than one organism can occur.

BOX 22-2 Empiric Therapy of Vulvovaginitis

 

Candida spp.

Trichomonas spp.

Bacterial vaginosis

First Choice

· Fluconazole, 150 mg orally × 1

· Miconazole, 1200 mg supp × 1; 200 mg supp qhs × 3 days; or 2% cream qhs × 7 days

· Clotrimazole, 500 mg supp × 1; 200 mg supp qhs × 3 days; 100 mg supp qhs × 7 days; 1% cream qhs × 7 days

· Butoconazole, 2% cream qhs × 3 days

· Terconazole, 0.4% cream qhs × 7 days

· Metronidazole, 2.0 g orally × 1

· Metronidazole, 500 mg orally twice a day × 7 days

· Metronidazole vaginal gel, 1 applicator intravaginally twice a day × 5 days

Second Choice

· Nystatin, 100,000 U supp qhs × 14 days

· Ketoconazole, 200 mg orally twice a day × 3-5 days

· Itraconazole, 200 mg orally twice a day × 1 day or 200 mg orally daily × 3 days

· Fluconazole, 100 mg orally daily × 1-3 days

· Metronidazole, 500 mg orally bid × 7 days

· Clindamycin, 300 mg orally twice a day × 7 days

· Clindamycin 2% vaginal cream 5 g intravaginally qhs × 7 days

Pregnancy

· Any topical treatment listed above

· Clotrimazole, 100 mg supp qhs × 14 days

· Metronidazole, 2.0 g orally × 1 (only in 2nd or 3rd trimester)

· Clindamycin, orally or cream as above

Rates of chlamydial infection have been estimated to be 5–30% (of women attending prenatal clinics). Pregnant women need prompt treatment because chlamydial infection can be transmitted to the infant; also, chlamydial genital infection has been associated with complications during labor such as an increased risk of premature rupture of membranes, preterm labor, and infants who are small for their gestational age.

Rates of asymptomatic infection with N gonorrhoeae have been estimated to be approximately 5% in women attending family planning clinics. Reported rates of infection during pregnancy are 2–7.3%. Asymptomatic infection at nongenital sites is important with N gonorrhoeae, because up to 40% of infected women have positive rectal cultures, and 22% have positive pharyngeal cultures. As with chlamydial infection, infection with N gonorrhoeae can be complicated by salpingitis, tubo-ovarian abscess, and PID. Disseminated gonococcemia can occur. In pregnancy, gonococcal infection has been associated with a higher rate of maternal and fetal morbidity.

Other causes of cervicitis include HSV, human papillomavirus, and other agents.

BOX 22-3 Microbiology of Cervicitis

More Frequent

· C trachomatis

· N gonorrhoeae

· Herpes simplex virus

· Human papillomavirus

Less Frequent

· Adenovirus

· Measles virus

· Cytomegalovirus

· Enterobius vermicularis

· Amoebae

· M tuberculosis

· Group B streptococci

· N meningitidis

 

Clinical Findings

  1. Signs and Symptoms.The diagnosis of cervicitis is suggested by the presence of a mucopurulent cervical discharge. Fever and pelvic pain may occur, particularly when the infectious process is complicated by salpingitis. On physical examination, erythema around the cervical os may be present; the os may also be raised and very friable. The clinical presentation cannot reliably distinguish among etiologic agents of cervicitis.
  2. Laboratory Findings.Gram stain of cervical discharge may show numerous (10–30) polymorphonuclear leukocytes per oil immersion field. The presence of gram-negative diplococci on the Gram stain confirms the diagnosis of N gonorrhoeae, but their absence does not rule out the possibility. Chlamydial infection is suggested by the presence of intracytoplasmic inclusions on Giemsa stain of cervical discharge. Fluorescent antibody staining and enzyme-linked immunosorbent assays (ELISA) to identify chlamydial antigens are also available, but positive results need to be confirmed by culture. LCR or PCR tests of cervical discharge or LCR tests of urine can help make a rapid diagnosis of chlamydia or gonorrhea infection. For both chlamydia and gonorrhea, culturing is also useful.

Differential Diagnosis

A diagnosis such as vaginitis is suggested by the vaginal discharge. Vaginal candidiasis, however, results in a typical whitish, curdy discharge; bacterial vaginosis (BV) and trichomonas vaginosis can result in a foul-smelling discharge, without the striking number of white cells found in cervicitis caused by chlamydial or gonorrheal infection.

Complications

Cervicitis caused by chlamydia or gonorrhea infection will progress to PID in 10–40% of women with cervicitis. Other complications include Fitz-Hugh-Curtis syndrome, or perihepatitis, which is characterized by fever and right upper quadrant pain. Chlamydial cervicitis in a pregnant woman can result in postpartum endometritis or, if she undergoes an abortion, postabortion infection. Premature rupture of membranes, preterm labor, and small-for-gestational-age infants can result from untreated chlamydial infection in pregnant women. Infection acquired by the infant during delivery leads to such complications as pneumonia in 40–50%, as well as nasopharyngeal infection and ophthalmia neonatorum.

Gonococcal infection can be complicated by bacteremia, leading to polyarthritis; endocarditis, myopericarditis, meningitis, and hepatitis can also occur. Infection in pregnant women has been associated with a higher incidence of prematurity, prolonged rupture of membranes, maternal peripartum fever, chorioamnionitis, and intrauterine growth retardation. In the newborn, gonococcal infection acquired at birth can result in pneumonia, nasopharyngeal infections, and ophthalmia neonatorum. Ophthalmia neonatorum prophylaxis consists of the instillation of 1% silver nitrate or erythromycin ointment in each eye.

Treatment

Penicillinase-producing N gonorrhoeae species are becoming more prevalent, making penicillin an ineffective choice for empiric therapy of cervicitis. Current recommendations are in Box 22-4. The recommendations recognize that simultaneous infection with C trachomatis and N gonorrhoeae is common, so that both organisms should be treated. Pregnant women should not receive tetracyclines. In addition, the newer macrolides have not been approved for use in pregnant women.

Prognosis

As stated previously, 10–40% of cervicitis cases caused by gonococcal or chlamydial infection in women will progress to PID, with the potential for infertility.

Prevention & Control

Both C. trachomatis and N. gonorrhoeae are reportable diseases. All sexual partners of the patient should be notified and treated promptly. The effects of untreated cervicitis in pregnant women and neonates can be minimized by the screening and prompt treatment of high-risk pregnant women when they are seen for prenatal care. Administration of erythromycin ointment or silver nitrate drops to neonates is an important step in prophylaxis against ophthalmia neonatorum.

BOX 22-4 Empiric Therapy of Cervictics

 

Adults & Adolescents

Pregnant Women

First Choice

· Ceftriaxone, 125 mg IM once, or cefixime, 400 mg orally once, PLUS doxycycline, 100 mg orally bid × 7 days

· Ceftriaxone, 125 mg IM once, or cefixime 400 mg, orally once, PLUS erythromycin 500 mg orally four times a day × 14 days

Second Choice

· Ceftriaxone, 125 mg IM once, or cefixime 400 mg, orally once, PLUS

o   Erythromycin, 500 mg orally × 7 days

o   Ofloxacin, 300 mg orally twice a day × 7 days

o   Azithromycin, 1.0 mg orally once

Penicillin Allergic

· Spectinomycin, 2.0 g IM once
PLUS

o   Doxycycline 100 mg orally twice a day × 7 days

o   Erythromycin, 500 mg orally four times a day for 7 days

o   Azithromycin, 1.0 g orally once

· Spectinomycin, 2.0 g IM once, PLUS erythromycin, 500 mg orally four times a day for 14 days

 

PELVIC INFLAMMATORY DISEASE

Essentials of Diagnosis

  • Risk factors: young sexually active women with multiple sexual partners, frequent sexual intercourse, and new sexual partners within the previous 30 days.
  • Signs: a pelvic mass may be discovered by examination or ultrasonography.
  • CDC minimum criteria: lower abdominal tenderness, cervical motion tenderness, and adnexal tenderness. Women who present with these symptoms should be treated empirically for PID in the absence of other diagnoses to explain their signs and symptoms.
  • CDC routine criteria: temperature of greater than 38.3°C, abnormal cervical or vaginal discharge, elevated erythrocyte sedimentation rate or C-reactive protein, and laboratory documentation of chlamydial or gonorrheal infection. The presence of these findings provides further support for the diagnosis of PID.
  • CDC elaborate criteria: histopathologic evidence of endometritis on biopsy, tubo-ovarian abscess on sonography or other radiologic tests, and laproscopic abnormalities consistent with PID. The presence of these findings provides the strongest support for the diagnosis of PID.

General Considerations

The vague term “pelvic inflammatory disease” is used to refer to acute, subacute, chronic, or recurrent infection caused by the ascent of cervical microorganisms to the endometrium, fallopian tubes, and other pelvic structures (Box 22-5). Therefore, salpingitis, tubo-ovarian abscess, pelvic peritonitis, and endometritis will be included in the term pelvic inflammatory disease or PID.

Women at risk for PID are those who have untreated cervicitis due to N gonorrhoeae or C trachomatis. It is estimated that 10–40% of women with these infections do not receive adequate treatment and, in these women, symptomatic PID subsequently develops. N gonorrhoeae accounts for 40–60% of women with acute salpingitis, whereas C trachomatis accounts for 20–25%. Other risk factors for PID include sexual activity among teenagers, a new partner in the previous 30 days, frequent intercourse, bacterial vaginosis, frequent douching, and tobacco and substance abuse. Use of an IUD slightly increases the risk of PID—it is thought that this increased risk is due to introduction of organisms into the upper reproductive tract at the time of insertion.

PID is an ascending, polymicrobial infection. Organisms most frequently implicated in PID are N gonorrhoeae, C trachomatis, and genital Mycoplasma spp. Anaerobes such as Peptococcus, Peptostreptococcus, and Bacteroides are often involved. E coli, Gardnerella vaginalis, H influenzae, and group B streptococcus are the most frequent aerobes involved.

BOX 22-5 Microbiology of PID

More Frequent

· Neisseria gonorrhoeae

· Chlamydia trachomatis

· Bacteroides spp.

· Peptostreptococcus

· Enterobacteriaceae

· Streptococci

· Mycoplasma hominis and Ureaplasma urealyticum

· Garneralla vaginalis

Less Frequent

· Actinomyces (in IUD users)

· Mycobacterium tuberculosis

Clinical Findings

  1. Signs and Symptoms.Lower abdominal, adnexal, and cervical motion tenderness are present in most patients with PID. (These are the CDC's minimum criteria for the diagnosis of PID.) The pain and tenderness are often associated with the onset of menses and may radiate to the back and down both lower extremities. A temperature of greater than 38.3°C and abnormal cervical or vaginal discharge provide further support for the diagnosis (see CDC routine criteria listed under “Essentials for Diagnosis” above).
  2. Laboratory Findings.Findings on laboratory studies, unfortunately, can be within normal limits. Abnormalities such as a leukocytosis, elevated sedimentation rate, or C-reactive protein can support the diagnosis, but their absence or presence does not confirm the diagnosis. Gram stain of cervical secretions may reveal the presence of gram-negative diplococci, suggesting N gonorrhoeaeas the causative organism. Culdocentesis may also be performed, and the fluid obtained should be examined for white cells; the presence of numerous white cells suggests PID, but appendicitis can also present in the same manner.
  3. Imaging.Ultrasonography of the pelvis may reveal an inflammatory mass consistent with tubo-ovarian abscess. Laproscopy remains the most accurate method for diagnosing PID and should be performed in cases in which the diagnosis remains uncertain. Hyperemia of the tubal surface, edema of the tubal walls, and an exudate on the tubal surface are consistent with PID. Cultures can be obtained at the time of laproscopic examination and may help guide therapy.

Differential Diagnosis

Appendicitis can present in a fashion similar to PID. A good history and physical examination may help differentiate between the two, although the diagnosis may not be established with certainty until the appendix is visualized at surgery. Ectopic pregnancy is suspected based on an elevated β-hcG level and ultrasound. Ultrasound may also be helpful in excluding entities such as ovarian cysts or ovarian torsion. Endometriosis can mimic chronic PID in that patients may present with complaints of chronic abdominal pain. However, they may also complain of irregular or heavy menstrual bleeding, which is more typical of endometriosis than of PID.

Nongynecologic problems such as irritable bowel syndrome or gastroenteritis should be suspected in patients who present with diarrhea and other bowel complaints. History and physical examination will also help differentiate cholecystitis from PID. Nephrolithiasis and pyelonephritis can also be differentiated from PID by location of abdominal pain, history, and urinalysis.

Complications

At least 25% of women with PID have serious sequelae, such as infertility, ectopic pregnancy, and chronic pelvic pain. Acute complications include pelvic peritonitis if there is rupture of an abscess or extension of the infectious process into the peritoneal space. Pelvic cellulitis with thrombophlebitis may result. Abscess, bacteremia, and septic shock may develop.

Treatment

Treatment should begin with empiric antibiotics as soon as the diagnosis is suspected. The CDC has published recommendations for the treatment of PID (Box 22-6). PID may be treated on an outpatient basis, with oral antibiotics. Ambulatory patients should, however, be reevaluated within 72 hours of beginning treatment. Under certain circumstances, hospitalization is recommended. The patient should be hospitalized when the diagnosis is uncertain and a surgical emergency such as acute appendicitis cannot be excluded; a pelvic or tubo-ovarian abscess is suspected; the patient is pregnant, an adolescent, or noncompliant; or the patient has failed or not tolerated outpatient therapy.

Regimen A (see Box 22-6) provides recommendations for treating gonorrhea and chlamydia. Regimen B provides recommendations for treating gonorrhea and chlamydia, as well as anaerobes. All sexual partners should be notified, treated empirically for chlamydia and gonorrhea, and tested for other sexually transmitted diseases.

BOX 22-6 Empiric Therapy of PID

 

Adults & Adolescents

Pregnant Women

Regimen A

· Outpatient treatment: Doxycycline, 100 mg orally twice a day × 14 days PLUS metronidazole, 500 mg orally twice a day × 14 days

· Inpatient treatment: Doxycycline, 100 mg IV or orally every 12 h PLUS one of the following:

o   Cefoxitin, 2.0 g IV every 8 h

o   Cefotetan, 2.0 g IV every 12 h

· Inpatient treatment only recommended Substitute erythromycin for doxycycline

Regimen B

· Outpatient treatment; Doxycycline, 100 mg orally twice a day × 14 days PLUS one of the following:

o   Ceftriaxone, 250 mg IM once

o   Cefoxitin 2.0 g IM PLUS probenicid, 1 g orally once

o   Other parenteral third-generation cepha-losporin (ceftizoxime or cefotaxime)

· Inpatient treatment: Clindamycin, 900 mg IV every 8 hours, PLUSgentamicin, 2 mg/kg loading dose IV or IM, then maintenance dose 1.5 mg/kg IV every 8 hours. Single daily dosing may be substituted. This regimen is preferred if tubo-ovarian abscess is suspected.

· Inpatient treatment only recommended. Substitute erythromycin for doxycycline.

Penicillin Allergic

· Clindamycin and gentamicin as above; do not use fluoroquinolones in adolescents younger than 16.

· Other alternatives: Ofloxacin, 400 mg IV every 12 h, PLUS metronidazole, 500 mg IV every 8 h; ciprofloxacin, 200 mg IV every 12 h plus doxycycline, 100 mg IV or orally every 12 h, plus metronidazole, 500 mg IV every 8 h.

· Clindamycin and gentamicin for adults

In the case of a tubo-ovarian abscess, the patient should be hospitalized and begun on broad-spectrum antibiotics that provide anaerobic coverage. Surgical intervention is indicated when there is failure to defervesce within 72 hours or when there is an increase in the size of the abscess. Most tubo-ovarian abscesses 4–6 cm in diameter resolve in response to medical therapy alone, but only 40% of abscesses larger than 10 cm respond to medical therapy alone.

Prognosis

A recent meta-analysis of 34 treatment regimens from 1966 to 1992 found cure rates to be above 90% for the commonly used treatment regimens, which form the basis for the current CDC treatment guidelines.

The incidence of infertility after the first bout of PID is approximately 12%. This rises to 25–35% after the second episode, and to 50–75% after three or more episodes. The risk of ectopic pregnancy increases to sevenfold that of a woman who has never had PID. Infertility rates are higher after tubo-ovarian abscess, with only 7–14% of women able to conceive.

Prevention & Control

Prevention consists of treating women and their sexual partners for cervicitis and aggressively screening women at high risk.

INFECTIONS AFTER GYNECOLOGIC SURGERY

Essentials of Diagnosis

  • Risk factors: more common in women who are premenopausal, undergoing abdominal versus vaginal hysterectomy, or of lower socioeconomic status and in women who undergo surgeries of longer duration or have bacterial vaginosis (BV) at the time of surgery.
  • Lower abdominal and pelvic pain and fever lasting from 2 days to several weeks after operation.
  • Variable tenderness on abdominal and pelvic examinations; palpable abdominal mass may be present with pelvic abscess.
  • Leukocytosis and elevated sedimentation rate; blood cultures and cultures of purulent cervical or wound drainage may be helpful.
  • Computed tomography and ultrasonography can help confirm the presence of an abscess.

General Considerations

The usual pathogens in gynecologic, postoperative infections are endogenous pelvic flora (Box 22-7). These are Lactobacillus spp., streptococci, Gardnerella vaginalis, Enterobacteriaceae, and anaerobes. Although Fusobacterium spp. and B fragilis are not usually present in the vaginal flora, they are often found in pelvic infections postoperatively. Factors such as hospitalization can cause a dramatic shift in the vaginal flora and predispose a patient to a postoperative pelvic infection. Use of spermicidal vaginal preparations, use of the female condom, douching, and the phase of the menstrual cycle can also affect the vaginal flora. Risk factors for the development of a postoperative infection include abdominal (versus vaginal) hysterectomy, lower socioeconomic status, premenopausal status, duration of surgery, and BV.

BOX 22-7 Microbiology of Gynecologic Postoperative Infections

More Frequent

· Streptococci

· Bacterioides

· Prevotella

· Gardnerella

· Enterobacteriaceae

Clinical Findings

Pelvic Cellulitis. Pelvic cellulitis is the most common infection after hysterectomy. Patients present on the second or third postoperative day with lower abdominal and pelvic pain, usually more severe on one side. The temperature is usually above 38.5°C. On abdominal and pelvic examination there is tenderness over the parametrial area. Cultures may be obtained from the vaginal cuff, although some believe that such cultures can be misleading because of contamination by vaginal flora.

Cuff Cellulitis and Abscess. Cuff cellulitis after hysterectomy usually manifests within 10 days of discharge from the hospital, with central lower abdominal and pelvic pain, vaginal discharge, and low-grade fever. Examination of the abdomen reveals slight suprapubic tenderness, and pelvic examination reveals no masses and only vaginal surgical margin tenderness. An inflammatory reaction at the surgical margin of the vaginal cuff is normal and does not require treatment.

Cuff abscess occurs when a well-localized collection develops above the vaginal cuff. These patients usually present on the second or third postoperative day with fever and a sense of fullness in the lower abdomen. Purulent material obtained from the surgical margin should be cultured aerobically and anaerobically.

Pelvic Abscess. Patients with pelvic abscesses are usually premenopausal women. They may present weeks after the original procedure. Typically patients may have received a course of antibiotics in the hospital for presumed pelvic cellulitis, but they relapse after discharge. Patients present with high spiking fevers, especially in the late afternoon or early evening, and may complain of pelvic or lower abdominal pain. There may be notable leukocytosis and considerable elevation in the erythrocyte sedimentation rate. Ultrasonography or computed tomography can confirm the presence of an abscess.

Treatment

Patients with pelvic cellulitis can be treated with single-agent antibiotic therapy. Cefotetan, cefoxitin, ampicillin/sulbactam, and ticarcillin/clavulanic acid are all reasonable choices (Box 22-8). In patients with β-lactam allergies, clindamycin and gentamicin can be used. Therapy should be continued until the patient is afebrile for at least 24 hours, and administration of oral antibiotics after parenteral treatment is generally thought to be unnecessary.

BOX 22-8 Empiric Therapy of Gynecologic Postoperative Infections

 

Pelvic Cellulitis

Cuff Cellulitis and Abscess

Pelvic Abscess

First Choice

· Cefotetan, 2.0 g IV every 12 h

· Cefoxitin, 2.0 g IV every 8 h

· Ampicillin/sulbactam, 3.0 g IV every 6 h

· Ticarcillin/clavulanic acid, 3.1 g IV every 6 h

· For cuff cellulitis: amoxicillin/clavulanic acid, 500 mg orally three times per day; need reevaluation in 72 h

· For cuff abscess, as for pelvic cellulitis

· Penicillin G 5 million units IV every 6 h or ampicillin 2.0 g IV every 6 h, PLUS gentamicin, 2.0 mg/kg IV load, then 1.7 mg/kg IV every 8 h

· Follow with amoxicillin/ clavulanic acid, 500 mg orally three times per day, or metronidazole, 500 mg orally three times per day, for 7 days

Second Choice

· Imipenem, 500 mg IV every 6 h

· Imipenem, 500 mg IV, every 6 h

Penicillin Allergic

· Clindamycin, 900 mg IV every 8 h, PLUS gentamicin, 2.0 mg/kg IV load, then 1.7 mg/kg IVevery 8 h

· Clindamycin and gentamicin as for pelvic cellulitis

· Clindamycin and gentamicin as for pelvic cellulitis

Patients with cuff cellulitis can be treated with oral antibiotics, such as amoxicillin, clavulanic acid, or both, as outpatients, as long as they monitor their temperature at home and are reevaluated within 72 hours (Box 22-8). For cuff abscess, parenteral antibiotic therapy is needed and should be continued until the patient has been afebrile for at least 24 hours (Box 22-8).

Treatment of pelvic abscesses requires parenteral antibiotic therapy (Box 22-8). Surgical drainage is not always necessary, because antibiotic therapy alone may be successful. Clindamycin and gentamicin are often used, because B fragilis and other gram-negative anaerobes are often isolated from pelvic abscesses. Parenteral antibiotics should be administered until the patient has been afebrile for 48–72 hours. Other parameters to monitor are the white blood cell count, amount of drainage, and abdominal pain and tenderness. Often recommended is treatment with oral antibiotics for 7 days after completion of a course of parenteral antibiotics. The patient should be reevaluated in 2 weeks to ensure that reaccummulation of the fluid has not occurred. Surgical drainage is necessary in patients who fail to respond to antibiotic therapy alone. Catheter drainage of the abscess should continue until the drainage ceases. Laporotomy is required in patients for whom all of the above measures fail.

Prevention & Control

The risk of these gynecologic postoperative infections can be reduced by treatment of BV in women who will be undergoing gynecologic procedures. Minimizing operative time and using the vaginal approach to hysterectomy can also help prevent these infections.

INTRAPARTUM & POSTPARTUM INFECTIONS

This section discusses major infections that occur during the intrapartum period (chorioamnionitis) and the postpartum period (postpartum endometritis, puerperal ovarian vein thrombophlebitis, and episiotomy infection), as well as during or after abortion.

CHORIOAMNIONITIS

Essentials of Diagnosis

  • Risk factors: preterm labor, prolonged rupture of membranes, multiple vaginal examinations, and preexisting bacterial vaginosis (BV); also, a hematogenous spread of organisms due to a bacteremic episode can occur.
  • Gram stain and culturing of amniotic fluid may be useful.
  • Characteristic leukocyte esterase and glucose concentrations in amniotic fluid.
  • Fever, tachycardia, and uterine tenderness in pregnant women.
  • Fetal tachycardia and heart rate abnormalities; evidence of fetal distress.

General Considerations

Chorioamnionitis refers to infection of the uterus and its structures during pregnancy. This syndrome is also referred to as intra-amniotic infection syndrome or IAIS. This infection is more common in women with preterm labor, occurring in up to 25% of such women; in women at term, the incidence is only 1 to 2%. It tends to occur in a setting of prolonged rupture of membranes or after multiple vaginal examinations, which allow the ascent of the causative organisms into the uterus and its contents (Box 22-9). Preexisting bacterial vaginosis is also a predisposing factor. Some cases are caused by the hematogenous spread of organisms into the uterus during a bacteremic episode. Organisms that have been cultured from amniotic fluid include vaginal flora such as Gardnerella vaginalis, Mycoplasma hominis, streptococci, and anaerobes. Gram-negative rods, especially E coli, and enterococci, are also commonly isolated. Infections with group B streptococci or E coli are particularly associated with the complication of bacteremia and are the most frequent isolates in neonates born to mothers with chorioamnionitis.

Clinical Findings

  1. Signs and Symptoms.The diagnosis of chorioamnionitis is made on clinical grounds. Asymptomatic cases make the diagnosis more difficult; 5–10% of women with preterm labor and intact membranes have symptomatic infection, whereas another 10% have subclinical infection. In patients with preterm premature rupture of membranes, up to 25% may have subclinical infection. Signs and symptoms usually seen in women with chorioamnionitis include fever, tachycardia, and uterine tenderness. The fetus may show signs of distress, including tachycardia and decreased variability in heart rate. Amniotic fluid is rarely foul smelling or purulent. Term pregnant women may experience dysfunctional labor, requiring induction or cesarean delivery for arrested progress of labor.
  2. Laboratory Findings.Amniotic fluid can be aspirated and analyzed to support the clinical diagnosis of chorioamnionitis. A Gram stain and culture of the fluid may be helpful. Increased leukocyte esterase activity and glucose concentration (< 10–15 mg%) may also be diagnostic.

BOX 22-9 Microbiology of Chorioamnionitis

More Frequent

· Enterobacteriaceae

· Enterococci

· Anaerobes

· Streptococci

Less Frequent

· Gardnerella vaginalis

· Mycoplasma hominis

· Herpes simplex virus

Complications

One complication of chorioamnionitis is dysfunctional labor, necessitating induction or cesarean delivery. Approximately three-quarters of women with chorioamnionitis require augmentation of labor with oxytocin. Cesarean delivery is required in approximately 40%. Left untreated, chorioamnionitis can result in bacteremia in the mother and pneumonia and bacteremia in the neonate.

Treatment

Antibiotics should be administered as soon as the diagnosis is made (Box 22-10). Prompt delivery, usually within 12 hours, is an essential part of treatment.

Prognosis

No maternal deaths from chorioamnionitis were reported in states in which such statistics were tracked from the 1980s to early 1992. However, postpartum infection in the mother is very common. Perinatal mortality is increased, with premature infants at higher risk than term infants.

Prevention & Control

Chorioamnionitis can be prevented or its incidence decreased by the treatment of bacterial vaginosis in pregnant women. Minimizing vaginal examinations and manipulations, especially in women with preterm labor or prolonged rupture of membranes will also decrease the risk.

POSTPARTUM ENDOMETRITIS

Essentials of Diagnosis

  • Risk factors: lower socioeconomic status, cesarean delivery, prolonged rupture of membranes and duration of labor, preexisting bacterial vaginosis (multiple vaginal examinations and use of internal fetal monitors).
  • Fever on first or second postpartum day; lower abdominal pain and uterine tenderness.
  • Leukocytosis and bacteremia possible.

BOX 22-10 Empiric Therapy of Chorioamnionitis

 

Adults & Adolescents

First Choice

· Ampicillin, 2.0 g IV every 6 hours, or penicillin G, 5 million units every 6 hours PLUS:

· Gentamicin, 2.0 mg/kg IV load, then 1.7 mg/kg IV every 8 h1

Second Choice

· Cefotetan, 2.0 g IV every 12 h

· Cefotaxime, 2 g IV every 8 h

· Cefoxitin, 2.0 g IV every 6 h

· Ampicillin/sulbactam, 3.0 g IV every 6 h

· Piperacillin/tazobactam, 3.375 g IV every 6 h

· Ticarcillin/clavulanic acid, 3.1 g IV every 6 h

· Imipenem, 500 mg IV every 6 h

Penicillin Allergic

· Gentamicin, 2.0 mg/kg IV load, then 1.7 mg/kg IV every 8 h1 PLUS one of the following:

o   Vancomycin, 1.0 g IV every 12 h

o   Erythromycin, 1.0 g IV, every 6 h

o   Clindamycin, 900 mg IV every 8 h

1Single daily dosing may be substituted.

General Considerations

Postpartum infection of the uterus is more common after cesarean delivery, with an incidence ranging from less than 10% on private services to 50% in indigent patients in large teaching hospitals. In comparison, the incidence of endometritis is only 0.9–3.9% after vaginal delivery. Other risk factors for postcesarean endometritis include longer duration of labor or of ruptured membranes, bacterial vaginosis, multiple vaginal examinations, and use of an internal fetal monitor.

Endometritis is a polymicrobial infection. Group B streptococci, Gardnerella vaginalis, E coli, anaerobes, and enterococci are common culprits (Box 22-11). Endometritis after vaginal delivery typically occurs 2 days to 6 weeks after delivery and has been associated with Chlamydia trachomatis. Group A β-hemolytic streptococci can cause endometritis as well, sometimes in association with toxic shock. Nosocomial transmission and outbreaks occur and require special isolation procedures. Ureaplasma urealyticum and Mycoplasma hominis have also been isolated from the endometrium and blood of affected patients.

Clinical Findings

  1. Signs and Symptoms.Generally fever develops on the first or second postpartum day. Lower abdominal pain is also usually present. On pelvic examination there may be uterine tenderness.
  2. Laboratory Findings.Leukocytosis is usually present. Transvaginal uterine cultures can be obtained, but results are often difficult to interpret because of the presence of contaminants. Blood cultures will yield growth in 10–20% of patients.

Differential Diagnosis

Other conditions such as puerperal ovarian vein thrombophlebitis (see next section), wound infection, or pelvic infection should be considered. Puerperal ovarian thrombophlebitis is rare but is usually associated with postcesarean endometritis. Half to two-thirds of patients will have a characteristic palpable abdominal mass. Wound infections or other pelvic infections should be considered when the patient fails to respond to antimicrobial therapy appropriate for the treatment of postpartum endometritis. Noninfectious causes of postpartum fever, such as breast engorgement and drug fever, should also be considered.

BOX 22-11 Microbiology of Postpartum Fevers

 

Postpartum Endometritis, POVT

Episiotomy Infection

More Frequent

· Group B streptococci

· Enterococci

· Aerobic streptococci

· Gardnerella vaginalis

· E coli

· Prevoltella bivia

· Bacteroides

· Peptostreptococci

· Streptococci

· Staphylococci

· Enterobacteriaceae

· Anaerobes

Less Frequent

· Ureaplasma urealyticum

· Mycoplasma hominis

· Chlamydia trachomatis (in late endometritis)

· Group A β-hemolytic streptococci

· Clostridium perfringens (myonecrosis)

Complications

Bacteremia can occur with postpartum endometritis and does occur in 10–20% of patients. However, it does not correlate with severity of illness or with prolonged recovery.

BOX 22-12 Empiric Therapy of Postpartum Fever

 

Postpartum Endometritis

Puerperal Ovarian Vein Thrombophlebitis

Episiotomy Infection

First Choice

· Cefoxitin, 2.0 g IV every 6-8 h

· Ticarcillin/clavulanic acid, 3.1 g IV every 6 h

· Imipenem, 0.5 g IV every 6 h

· Ampicillin/sulbactam, 3.0 g IV every 6 h

· Piperacillin/tazobactam, 3.375 g IV every 6 h

· One of the above PLUS doxycycline, 100 mg IV, every 12 h, if chlamydial endometritis

· Cefoxitin, 2.0 g IV every 6-8 h

· Ticarcillin/clavulanic acid, 3.1 g IV every 6 h

· Piperacillin/tazobactam, 3.375 g IV every 6 h

· Ampicillin/sulbactam, 3.0 g every 6 h

· One of the above PLUS heparin IV

· Clindamycin, 450-900 mg IV every 8 h, and ampicillin, 2.0 g IV every 6 h, and gentamicin, 2.0 mg/kg IV load, then 1.7 mg/kg IV every 8 h PLUS surgical debridement

· Clindamycin, 900 mg IV every 8 h and penicillin G, 24 million units IV in 4-6 divided doses, per day PLUS surgical debridement, hyperbaric oxygen, or both if clostridial nfection

Second Choice

· Clindamycin, 450-900 mg IV every 8 h PLUS one of the following:

o   Gentamicin, 2.0 mg/kg IV load, then 1.7 mg/kg every 8 h1

o   Cefotaxime, 2.0 g IV every 8 h

o   Ceftriaxone, 2.0 g IV every 24 h

· Imipenem, 500 mg IV every 6 h

· Ceftriaxone, 2.0 g IV every 12 h if clostridial infection

Penicillin Allergic

· Clindamycin, 450-900 mg IV every 8 h, and gentamicin, 2.0 mg/kg IV load, then 1.7 mg/kg every 8 h

· Clindamycin and gentamicin as for postpartum endometritis

· Erythromycin, 1.0 g IV every 6 h if clostridial infection

1Single daily dosing may be substituted.

Treatment

Mild to moderately severe postpartum endometritis is treated with an extended-spectrum penicillin (ticarcillin/clavulanic acid or ampicillin/sulbactam) or second-generation cephalosporin (cefotetan or cefoxitin) (Box 22-12). Severe pospartum endometritis can be treated with clindamycin and gentamicin, especially after cesarean delivery. Therapy should be continued until the patient is afebrile for 24 hours, is free of abdominal pain, and no longer has a leukocytosis. There is no need to continue oral antibiotics after the patient is discharged from the hospital. However, women known to have chlamydial endometritis should receive oral erythromycin or doxycycline for a full course even when they have responded well to parenteral therapy as above.

Several possibilities should be considered when a patient fails to respond to antimicrobial therapy. First, the diagnosis should be questioned and other diagnoses should be considered. Second, the treatment regimen may not cover drug-resistant pathogens. Multi-drug-resistant anaerobes are emerging and do account for some treatment failures. Third, an undrained abscess may be present. Finally, enterococcal species superinfection may exist. Enterococcal superinfection should be considered when enterococci are isolated in pure culture or in heavy growth from an endometrial specimen. In the past, ampicillin plus gentamicin were effective for enterococcal infection. However, the prevalence of β-lactam resistance, high-level aminoglycoside resistance, and, more recently, even vancomycin resistance complicates empiric treatment of enterococcal infection. Depending on the incidence of multiple-drug-resistant enterococci at a given locale, vancomycin plus gentamicin may be the best choice for suspected enterococcal infection until susceptibility test results are available. In cases in which the isolate is also resistant to vancomycin, infectious disease experts should be consulted. Cephalosporins have no role in the treatment of enterococcal infection but may be needed to treat other suspected pathogens.

Prognosis

The prognosis is usually good, because intravenous antibiotic therapy is quite effective.

Prevention & Control

Prophylactic antibiotics should be administered to any patient who is undergoing a cesarean section after labor or rupture of membranes, regardless of duration. Cefazolin, 1–2 g IV after the umbilical cord is clamped, with a second dose given 4 hours later in high-risk patients, is adequate prophylaxis. Alternatively, metronidazole or clindamycin and gentamicin can be given to patients with a β-lactam allergy. Even with prophylactic antibiotics, postpartum endometritis will develop in 15% of women.

PUERPERAL OVARIAN VEIN THROMBOPHLEBITIS (POVT)

Essentials of Diagnosis

  • Acute onset of fever, chills, and lower abdominal pain.
  • Sausage-shaped or ropelike abdominal mass on physical examination.
  • Computed tomography (CT), Doppler ultrasonography, and magnetic resonance imaging (MRI) can help confirm the diagnosis.

General Considerations

Puerperal ovarian vein thrombophlebitis (POVT) occurs in the postpartum period and is a result of thrombosis of the ovarian veins (Box 22-11). It is usually associated with postcesarean endometritis, but it can occur in the absence of endometritis. Its incidence is 1 per 2000 deliveries or 1–2 per 100 patients with postpartum infection. In many patients, POVT is diagnosed after failure to respond to a therapeutic trial of antibiotics for presumed postpartum endometritis.

Clinical Findings

  1. Signs and Symptoms.The onset of symptoms usually occurs 2–4 days postpartum and is usually acute. Patients experience pain in the lower abdomen, often on the right side. Fever and chills also occur. The degree of tachycardia that occurs is often disproportionate to the degree of temperature elevation. An abdominal mass can be palpated in half to two-thirds of patients and is sausage shaped or ropelike. The mass usually extends from the right uterine cornua to the upper abdomen. Signs of respiratory distress may be present if pulmonary embolization has occurred.
  2. Laboratory Findings.Laboratory studies are not helpful in diagnosis. Leukocytosis may be present, and coagulation studies are sometimes abnormal. Results of blood cultures are usually sterile.
  3. Imaging.Computed tomography, duplex Doppler ultrasonography, and magnetic resonance imaging can be used to confirm the diagnosis.

Differential Diagnosis

Puerperal ovarian vein thrombophlebitis must be differentiated from postpartum endometritis. Indeed, many women with POVT are first diagnosed with postpartum endometritis. When appropriate therapy fails, the correct diagnosis of POVT often is made. Other diagnoses to be considered include postpartum episiotomy infection (see next section), PID, pelvic abscess, or other nongynecological sources of fever.

Complications

The complication of pulmonary embolization should always be considered, especially if tachypnea, hypoxia, chest pain, or other signs of respiratory distress develop.

Treatment

Continuous intravenous anticoagulation with heparin is important. The optimal duration of anticoagulation is not known, but many clinicians treat for 7–10 days (if pulmonary embolization has not occurred). Administration of broad-spectrum antibiotics against common pelvic pathogens is also helpful (Box 22-12).

 

Prognosis, Prevention, & Control

The prognosis with POVT is good when pulmonary embolization has not occurred. Early mobilization after delivery and prophylactic anticoagulation for high-risk patients can help reduce the risk of POVT.

EPISIOTOMY INFECTIONS

Essentials of Diagnosis

  • Edema and erythema along the site of episiotomy.
  • More serious infections involving deeper layers of tissue may not manifest with edema and erythema of the overlying skin.
  • Local pain; if there is more serious infection, fever and chills along with other systemic complaints.

General Considerations

Infections of episiotomies are rare, with an incidence of 0.1%. There is a higher risk of infection, up to 1–2%, with episiotomies that involve third- or fourth-degree extensions. A classification scheme for episiotomy-related infections separates such infections based on their depth of infection. A simple episiotomy infection is a localized infection that involves only the skin and superficial fascia along the incision. Edema and erythema may be present along the incision site. Causative organisms include streptococci, staphylococci, Enterobacteriaceae, and anaerobes (Box 22-11). A superficial fascia infection without necrosis can present without very striking clinical signs or symptoms except that the skin is edematous and erythematous along the incision. Superficial fascia infection with necrosis (or necrotizing fasciitis) involves infection of the superficial fascia that spreads into the fascial clefts overlying the deep fascia. The skin overlying the wound may not appear eyrthematous or edematous, but the patient will have considerable systemic manifestations of infection. Skin involvement occurs after vessels supplying the overlying skin are thrombosed. Myonecrosis is extremely rare and refers to infection beneath the deep fascia, involving muscle. Clostridium perfringens is the usual etiologic agent. Myonecrosis can occur as a complication of an inadequately treated or untreated necrotizing fasciitis. It can also occur in the subgluteal muscles surrounding the hip joint or psoas muscle after introduction of organisms by a paracervical or pudendal needle.

Clinical Findings

  1. Signs and Symptoms.As noted previously, the patient will usually have localized edema and erythema along the incision site if the infection is a simple infection. When necrotizing fasciitis occurs, the skin may not appear erythematous or edematous at all. However, the patient may experience extreme systemic manifestations such as high fever and chills. Pain is often more severe than clinical signs of infection. Definitive diagnosis of necrotizing fasciitis is made at surgery when the surgeon finds extensive undermining of surrounding tissues and lack of resistance in the superficial fascial plane to probing with a blunt instrument. Necrotizing fasciitis is a medical emergency and requires immediate surgical intervention.
  2. Laboratory Findings.Laboratory findings will vary with the extent of infection; a patient with a simple episiotomy infection may have very few laboratory abnormalities, whereas a patient with myonecrosis can present with severe hypotensive shock.
  3. Imaging.Imaging is not necessary except in unusual cases. The diagnosis is made by inspection of the episiotomy site in cases of simple and superficial infections and by surgical exploration in more serious infections.

Complications

Sepsis as well as pelvic abscess and extensive necrosis of pelvic structures may occur if early infections are not diagnosed and treated promptly.

Treatment

Simple infections may be treated with an oral antibiotic such as amoxicillin/clavulanic acid. Optimal therapy for more serious infections involves both systemic antibiotics and surgical débridement (Box 22-12).

Prognosis

For simple episiotomy infections, the prognosis is quite good, with few complications seen. More serious infection such as myonecrosis can have a graver prognosis.

SEPTIC ABORTION

Essentials of Diagnosis

  • Occurs in the presence of retained products of conception or operative trauma; more likely when pregnancy is advanced, technical difficulties during the procedure occur, and a sexually transmitted pathogen is present.
  • Fever, chills, abdominal pain, or vaginal bleeding within 4 days of abortion.
  • Tachycardia, tachypnea, or abdominal tenderness on physical examination. The patient may be in frank hypotensive shock.
  • Sanguinopurulent discharge and uterine tenderness on pelvic examination.
  • Leukocytosis, anemia, or positive cervical or blood cultures.
  • Pelvic ultrasound can confirm the presence of retained products of conception.

 

General Considerations

Postabortion infection can occur in the presence of retained products of conception or operative trauma. It is an ascending process, and risk factors include more advanced pregnancies, technical difficulties, and the presence of a sexually transmitted pathogen. The most common causative organisms are endogenous pelvic flora (Box 22-13). However, Clostridium perfringens can be the causative agent of postabortion infection and can cause a characteristic presentation of massive intravascular hemolysis.

Clinical Findings

  1. Signs and Symptoms.Patients commonly present within 4 days of the procedure with fever, chills, abdominal pain, and vaginal bleeding. Often there has been passage of placental tissue.

Patients with mild infection or simple endometritis may appear mildly ill with low-grade fever and mild uterine tenderness. Patients with more serious infection will present with severe systemic manifestations, sometimes in hypotensive shock.

On physical examination, there will be elevated temperature, tachycardia, tachypnea, and uterine tenderness. Sanguinopurulent discharge may be evident on pelvic examination. The patient with bacteremia and resultant hypotensive shock may be agitated and disoriented. The patient with C perfringens infection may display jaundice, mahogany-colored urine, and striking anemia caused by intravascular hemolysis.

  1. Laboratory Findings.A complete blood count will reveal leukocytosis and sometimes hemolytic anemia, which is severe with C perfringens.Gram stain and culturing of cervical material may reveal the causative organism. Blood cultures should be obtained and may reveal the causative organism in the patient with bacteremia.
  2. Imaging.Pelvic ultrasound can be performed to confirm the presence of retained products of conception.

Differential Diagnosis

Other diagnoses to be considered in this setting include appendicitis, pyelonephritis, pelvic abscess, and noninfectious causes of fever.

BOX 22-13 Microbiology of Septic Abortion

More Frequent

· Bacteroides

· Group A and B streptococci

· Enterobacteriaceae

· Chlamydia trachomatis

Less Frequent

· Clostridium perfringens

Complications

Postabortion infection can progress to bacteremia and frank shock. Perforation of the uterus may occur both during abortion and during curettage. Pelvic or adnexal abscesses may result from untreated infection. Necrotizing myometritis with Clostridium spp. can also occur.

Treatment

Simple postabortion endometritis requires only oral doxycycline (Box 22-14). More serious infections require curettage and parenteral antibiotic therapy. Laproscopy or laporotomy and hysterectomy may be necessary when the condition fails to respond to curettage and appropriate antibiotics.

Prognosis

The prognosis is generally good for simple postabortion endometritis. Patients in whom therapy fails have a high risk of infertility owing to the necessity of hysterectomy, whereas patients with C perfringens infection may have a grave prognosis.

Prevention & Control

Screening for sexually transmitted diseases before abortion may decrease the risk of acquiring this infection. Performing abortion procedures in medical facilities with proper infection control has resulted in a dramatic decline in the number of these infections in the past decade.

INFECTIONS OF SPECIAL CONCERN DURING PREGNANCY

GROUP B STREPTOCOCCUS (GBS)

Essentials of Diagnosis

  • High fever after delivery or uterine and adnexal tenderness.
  • Early neonatal infection presents as fever, lethargy, respiratory distress, jaundice, and hypotension. Late-onset neonatal infection presents as meningitis and, less commonly, as bacteremia.
  • Isolation of group B streptococcus (GBS) from neonatal or maternal blood cultures or a history of maternal colonization with GBS.

General Considerations

GBS is estimated to cause approximately 15,000 infant and 48,000 maternal infections in the United States each year. GBS causes postpartum endometritis in the mother and early-onset disease (bacteremia) or late-onset disease (meningitis) in the neonate. It is also the cause of intrapartum chorioamnionitis, urinary tract infections, and postpartum wound infections. GBS can be part of the normal fecal and vaginal flora, and asymptomatic carriage rates vary from 5–40%, depending on the culture technique used and the population studied.

BOX 22-14 Empiric Therapy of Septic Abortion

 

Adults & Adolescents

First Choice

· Doxycycline, 100 mg every 12 h IV or orally PLUS one of the following:

o   Cefoxitin, 2.0 g every 6-8 h IV

o   Ticarcillin/clavulanic acid, 3.1 g every 6 h

o   Imipenem, 0.5 g every 6 h IV

o   Meropenem, 1.0 g every 8 h IV

o   Ampicillin/sulbactam, 3.0 g every 6 h IV

o   Piperacillin/tazobactam, 3.375 g every 6 h IV

· Doxycycline, 100 mg orally every 12 h for mild symptoms

Second Choice

· Clindamycin, 450-900 mg IV every 8 h PLUS one of the following:

o   Gentamicin, 2.0 mg/kg IV load then 1.7 mg/kg IV every 8 h1

o   Cefotaxime, 2.0 g IV every 8 h

Penicillin Allergic

· Clindamycin, 450-900 mg IV every 8 h, and gentamicin, 2.0 mg/kg IV load, then 1.7 mg/kg every 8 h1

1Single daily dosing may be substituted.

Risk factors for carriage of GBS include use of an intrauterine device and age younger than 20 years. Although vaginal colonization can be transient, approximately one-third of pregnant women are colonized throughout their pregnancy. Transmission to the neonate is estimated to occur 60% of the time when the mother is colonized. Early-onset disease is probably acquired by the neonate in utero or as the neonate passes through an infected birth canal. The number of cases of early-onset disease is estimated to be 1.3–3.7/1000 live births. Early-onset disease tends to occur in premature and low-birth-weight babies in the first 6–12 hours of life. Additional risk factors for early-onset disease include premature rupture of membranes, multiple births, maternal chorioamnionitis, maternal GBS bacteremia, and low levels of maternal type-specific capsular antibodies. The overall mortality is now approximately 15%.

Late-onset disease occurs in 0.5–1.8/1000 live births, and the mortality is approximately 10%. It usually presents 1 or more weeks after birth. The mode of transmission is by contact with hospital nursery personnel. Typically the maternal history and the birth are not complicated, and most affected infants are full term.

Clinical Findings

The neonate will display nonspecific signs such as fever, lethargy, respiratory distress, jaundice, and hypotension. There may be seizure activity if the onset is late. Isolation of the organism from blood or other sites (cervical cultures) is diagnostic. A history of maternal colonization may be obtained.

Treatment

Treatment of GBS infection in the mother and neonate includes empiric broad-spectrum antibiotics until culture results are known. Penicillin is the antibiotic of choice, once cultures are confirmed.

Prevention & Control

Several groups have shown that treatment of GBS in the mother with intrapartum antibiotics helps reduce the incidence of neonatal GBS disease by about 33–50%. Several groups have published guidelines for prophylaxis (Box 22-15). The American Academy of Pediatrics in 1992 recommended universal screening of all women for GBS by obtaining cultures from the distal vagina and anorectum at 26–28 weeks' gestation. Intrapartum prophylaxis should then be given to GBS carriers who are

P.304


at risk for neonatal sepsis. Risk factors include preterm labor, preterm premature rupture of membranes, multiple gestation, intrapartum fever, and real or anticipated membrane rupture for a period of 18 or more hours.

BOX 22-15 Prophylaxis of Group B Streptococcal Infection

First Choice

· Ampicillin, 2.0 g once IV

· Penicillin G, 5 million units IV, then 2.5 million units every 4 h IV

· Penicillin potassium, 500 mg every 6 h orally if delivery not imminent

Second Choice

· Erythromycin, 1.0-2.0 g IV every 6 h

· Vancomycin, 1.0 g IV every 12 h

· Clindamycin, 600 mg IV every 6 h

Penicillin Allergic

· Erythromycin, 1.0-2.0 g IV every 6 h

The American College of Obstetricians and Gynecologists (ACOG) 1992 guidelines did not advocate routine screening but rather the administration of intrapartum antibiotics (penicillin G, ampicillin, or erythromycin) based on the presence of certain risk factors: preterm labor, preterm premature rupture of membranes, prolonged membrane rupture, a sibling affected by GBS disease, and intrapartum maternal fever. Currently, ACOG advocates following their 1992 guidelines or obtaining routine cultures in women beginning at 32 weeks' gestation and treating with penicillin G those women with positive cultures at the time of labor.

The CDC advocates either the 1992 ACOG guidelines or screening all women at 35–37 weeks' gestation and administering intrapartum penicillin G for all culture-positive women. Several studies have shown, however, that despite the many guidelines, there is significant variability in screening and treatment among practitioners.

TERATOGENIC INFECTIONS & OTHER INFECTIONS OF CONCERN IN PREGNANCY

Certain infections, whether primarily acquired or reactivated during pregnancy, are of special concern. These infections are important either because of their teratogenic effects or the morbidity and mortality with which they are associated in neonates. The teratogenic infections covered in this section are syphilis, toxoplasmosis, cytomegalovirus, rubella, and varicella. Measles, mumps, and parvovirus are discussed as well, as they can cause significant morbidity in the neonate. Herpesvirus and papillomavirus are also discussed, as they can be very common problems during pregnancy. Tables 22-2 and 22-3 describe these infections and summarize their treatment, prevention, and control during pregnancy and afterward.

SYPHILIS IN PREGNANCY

Esentials of Diagnosis

  • Presentation similar to nonpregnant women.
  • Late abortion after fourth month of pregnancy, stillbirth, or congenital syphilis in the neonate.

General Considerations

Congenital syphilis has become more of a problem in recent years, owing to the dramatic increase in the number of cases of syphilis. Pregnancy in a woman with syphilis may have any of the following outcomes: late abortion after the fourth month of pregnancy, stillbirth, a congenitally infected infant, or a healthy uninfected infant. There is no difference in presentation or diagnosis of syphilis in pregnant women. Any suspicious lesion in a pregnant woman should be examined, and serologic testing over a 6–8 week period should be performed. A positive nontreponemal (rapid plasma reagin [RPR] or Venereal Disease Research Laboratory [VDRL]) test result should be followed up with a fluorescent treponemal antibody absorption (FTA-ABS) test for confirmation.


A nonreactive or borderline FTA-ABS test result in light of a positive nontreponemal test result should prompt a search for the cause of a biologic false-positive test, such as malaria, leishmaniasis, hepatitis, leprosy, antiphospholipid syndrome, or lupus anticoagulant.

Table 22-2. Infections of special concern during pregnancy.

 

Maternal Diagnosis

Fetal Diagnosis

Risk of Transmission

Congenital/Fetal Effects

Syphilis

Positive RPR or VDRL confirmed by FTA-ABS

Positive IgM, positive PCR on amniotic fluid

Almost 100% if mother has primary or secondary syphilis; 80% in early latent syphilis

Stillbirth, late abortion; hepatosplenomegaly, deafness, jaudice, interstital keratitis, congenital stigmata

Toxoplasmosis

Serology (IgG, IgM)

Elevated IgM, consistent clinical presentation, positive PCR on amniotic fluid

17% in first trimester;
65% in third trimester;
40% overall

Microcephaly, hydrocephalus, chorioretinitis, blindness

Cytomegalovirus (CMV) infection

Serology or isolation of CMV in urine or blood. PCR on blood

CMV in urine or blood; PCR on amniotic fluid, blood, CSF

Difficult to estimate due to large number of subclinical infections; incidence of congenital infection during pregnancy is about 1%. 40–60% of breastfed infants become seropositive.

Hepatosplenomegaly, jaundice, chorioretinitis, hearing loss, microcephaly. Most often results from primary maternal infection; majority of congenital infections result from maternal reactivation of infection and are not associated with sequelae

Rubella

Serology (IgM and IgG); viral isolation can take up to 6 weeks

Serology; persistence of IgG after 1 month of life

80% in first trimester, 25% second trimester; risk of congenital anomalies greatest with infection in the first trimester

Hepatosplenomegaly, jaundice, pneumonitis, microcephaly, cataracts, heart abnormalities, glaucoma, mental retardation

Varicella-zoster virus (VZV) infection

Serology, DFA of preparation of lesions

Culture of lesions; DFA of infected cells, if any; serology

5-7% of pregnant women with VZV

Growth retardation, limb aplasia, cutaneous scarring, hearing loss, chorioretinitis, cataracts; neonatal chickenpox—benign course or disseminated infection

Herpes simplex virus

Isolation of virus, DFA preparation of lesions, PCR

Same as for maternal diagnosis

Difficult to estimate owing to high number of women who are asymptomatic shedders of virus. Incidence of congenital infection is < 0.1%.

Localized skin disease, encephalitis, keratoconjunctivitis, chorioretinitis, disseminated disease

If the mother has primary or secondary syphilis, it is very likely that the infant will be infected, as the spirochetemia that accompanies primary or secondary syphilis is usually quite intense. If the mother has early latent syphilis, there is an 80% chance of fetal infection. Once spirochetes enter the fetal circulation, dissemination to the tissues rapidly follows. The most severe cases of fetal infection follow maternal infection early in pregnancy, and fetal death may occur if the burden of spirochetemia is high. If spirochetemia occurs later in pregnancy, the child may be stillborn or die of congenital syphilis in the neonatal period. When intrauterine infection occurs relatively late in pregnancy, the child may be born with mild or no symptoms of infection. Signs and symptoms of infection may develop 2–4 weeks after birth. Occasionally congenital infection does not become apparent until several months have passed. It is also possible for the infant to acquire infection upon passage through the birth canal, by contact with a syphilitic lesion. Infants who acquire infection in this manner often have a presentation similar to sexually acquired syphilis.

Clinical Findings

  1. Signs and Symptoms.Pregnancy does not affect the presentation of syphilis. Please see Chapters 15 and 65 for a more detailed discussion of syphilis.

Table 22-3. Treatment, prevention, and control of infections of special concern in pregnancy.

 

Treatment of Mother

Treatment of Neonate

Prevention & Control

Syphilis

As for nonpregnant women. Follow with monthly VDRL or RPR titers and retreat if four-fold or higher increase in titers.

Aqueous crystalline penicillin G 100,000–150,000 U/kg/d in 3 divided doses for 14 days

Screening and treatment of high risk women

Toxoplasmosis

Spiramycin, 1.5 twice a day orally throughout pregnancy; or pyrimethamine, 25 mg once daily orally, plus sulfa-diazine, 1.0 g 4 times per day orally plus folinic acid, 6 mg 3 times/week orally, thoroughout pregnancy

If overt infection: pyrimethamine, 2 mg/kg orally every 2-3 d, and sulfadiazine, 100–200 mg/kg/d orally, and folinic acid, 5 mg orally every 3 days for 6 months, then 6 months of alternating monthly herapy with spiramycin. If the diagnosis is in question, administer pyrimethamine for 21 days, then spiramycin until a definitive diagnosis is made

Cook meat thoroughly; wash fruits and vegetables thoroughly; avoid contact with cat litter

CMV

None

None

Vaccine under investigation

Rubella

None

None

Vaccination of all women of child-bearing age

VZV

Acyclovir, 10 mg/kg every 8 h IV or 800 orally 5 times per day; VZIg, if given, should be given within 96 h of exposure

Acyclovir, 10 mg/kg every 8 h

Avoid exposure of nonimmune pregnant women to chickenpox or zoster

HSV

Acyclovir, 200 mg orally 5 times per day for 7–10 days for primary infection; 200 mg orally 5 times per day for 5 days for recurrences

Acyclovir, 10 mg/kg IV every 8 h

Cesarean delivery if active lesions

 

  1. Laboratory Findings.Darkfield examination of a chancre may show T pallidum.Nontreponemal serology, VDRL or RPR, will be positive. Such tests should be followed up with an FTA-ABS for confirmation. If the findings on FTA-ABS are negative, the clinician should search for a cause of a biologic false-positive treponemal test. Polymerase chain reaction (PCR) on amniotic fluid has been shown to be very sensitive and specific. Spirochetes may be recoverable from fetal blood or from amniotic fluid. Maternal immunoglobulin G (IgG) that has crossed the placenta will cause positive results on nontreponemal and treponemal tests of cord and fetal blood. Serial quantitative serologic testing of the infant may show a rising titer—this is consistent with congenital infection.

Differential Diagnosis

Cutaneous lesions in the newborn are not always caused by syphilis. Erythroblastosis fetalis, congenital toxoplasmosis, rubella, and cytomegalovirus (CMV) infection can also cause cutaneous lesions and fetal abnormalities.

Treatment

The treatment of a pregnant woman with syphilis is the same as that in the general population. Some clinicians recommend that penicillin-allergic pregnant patients be desensitized to penicillin, as penicillin is thought to be the only antibiotic that reliably treats the fetus as well as the mother. Some practitioners recommend a second dose of benzathine penicillin G 1 week after the initial dose, especially in the third trimester. After treatment, the woman should be monitored with quantitative serologic titers and re-treated if there is a fourfold or higher increase in the titer.

The neonate should receive aqueous crystalline penicillin G (100,000–150,000 U/kg/d in 3 divided doses) for 14 days or aqueous procaine penicillin G intramuscularly (IM) for 14 days.

Prognosis, Prevention, & Control

In a series of 403 pregnancies in women with positive serology for syphilis, 18% resulted in congenital syphilis (half of the babies were stillborn neonates). Of the mothers who gave birth to babies with congenital syphilis, 81% had not received any treatment for syphilis. Prevention of congenital syphilis requires prompt treatment of mothers who have syphilis as well as aggressive screening for syphilis in high-risk populations.

TOXOPLASMOSIS IN PREGNANCY

Essentials of Diagnosis

  • Maternal infection as mild or subclinical flulike illness; sometimes cervical lymphadenopathy, fatigue, malaise, or atypical lymphocytosis.
  • Infants can be asymptomatic or have chorioretinitis, blindness, deafness, seizures, microcephaly, hydrocephalus, fever, jaundice, hepatosplenomegaly, pneumonitis, or coagulopathy.
  • Serologic diagnosis of mother and newborn; fetal ultrasound can be performed after maternal infection is confirmed. PCR testing on amniotic fluid can also be performed.

General Considerations

Toxoplasmosis is caused by the intracellular parasite Toxoplasma gondii. The prevalence of disease varies by geographic location. Congenital infection is relatively uncommon in the United States, where screening is not routinely done, but is very common in France, where universal screening is mandatory. Please see Chapter 81 for more discussion of toxoplasmosis in the general population.

In pregnancy, infection is often subclinical or mild and self-limited. A mononucleosis-like syndrome can occur, with fatigue, malaise, cervical lymphadenopathy, and atypical lymphocytosis. Pregnancy does not appear to predispose to more severe illness, but there may be an increased incidence of pregnancy-related complications in women who acquire primary infection while pregnant. The overall risk of fetal infection is 40%, and the later in pregnancy the woman acquires infection, the higher the risk of transmission to the fetus. The earlier in pregnancy the woman acquires infection, however, the higher the risk of severe manifestations of infection in the fetus. Transmission rates have been reported as 17% in the first trimester and 65% in the third trimester.

Clinical Findings

  1. Signs and Symptoms.As stated, maternal infection may be very mild. In the infected infant, however, disease can be severe. There may be chorioretinitis, blindness, deafness, seizures, microcephaly, hydrocephalus, fever, jaundice, hepatosplenomegaly, pneumonitis, and coagulopathy. In many asymptomatic infants, chorioretinitis can develop, which may lead to blindness in adolescence or adulthood.
  2. Laboratory Findings and Imaging.Diagnosis depends on serology, both in the mother and infant. The mother's IgG and IgM titers should be measured. If titers are elevated and consistent with maternal infection, fetal ultrasound should be performed, looking for intracerebral calcifications, microcephaly, aqueductal stenosis, and hydrocephalus. After birth, infants suspected of having congenital toxoplasmosis should have serial serologies. The presence of IgM antibody indicates acute infection, whereas declining IgG titers in the absence of IgM antibodies indicate passive transfer of maternal antibodies. PCR tests on amniotic fluid appear to be as accurate as conventional diagnostic tests.

Differential Diagnosis

Congenital toxoplasmosis should be differentiated from congenital syphilis, erythroblastosis fetalis, congenital rubella, and cytomegalovirus infection (CMV).

Treatment

Many practitioners consider documentation of first-trimester fetal infection a reason for termination of pregnancy. Maternal infection between conception and the 24th week of gestation may also justify termination of the pregnancy.

When maternal infection is confirmed, treatment with spiramycin (1.5 g twice a day orally) should be started and continued throughout the pregnancy. Such treatment has been reported to reduce the incidence of fetal infection by 60%. Toxicity is minimal, and although generally available in Europe, spiramycin can be obtained in the United States only by application to the U.S. Food and Drug Administration (FDA). Pyrimethamine and sulfadiazine also can reduce the rate of transmission to the fetus and prevent progressive fetopathy but are associated with more toxicity. Folinic acid, 6 mg orally 3 times a week, should be given with this regimen. Because of the potential for teratogenicity, some clinicians recommend that pyrimethamine be begun only after the 14th week of gestation.

In the neonate, treatment of overt toxoplasmosis involves 6 months of therapy with pyrimethamine plus sulfadiazine and folinic acid and an additional 6 months of alternating monthly therapy with spiramycin. Healthy infants suspected of having congenital infection can be treated with pyrimethamine and sulfadiazine for 21 days followed by spiramycin until a definitive diagnosis is established.

Prognosis

The prognosis is good for the mother; 15% of infants born to infected mothers will be severely affected.

Prevention & Control

Prevention of toxoplasmosis can be achieved by thoroughly cooking meat, thoroughly washing fruits and vegetables, and avoiding contact with cat litter and soil or other materials contaminated with cat feces.

CYTOMEGALOVIRUS IN PREGNANCY

Essentials of Diagnosis

  • The mother may be asymptomatic or have a mononucleosis-like illness.
  • The infant may demonstrate cytomegalic inclusion disease, characterized by hepatosplenomegaly, jaundice, thrombocytopenia, chorioretinitis, cerebral calcifications, and microcephaly. Interstitial pneumonitis may develop.
  • Maternal infection may be suggested by characteristic atypical lymphocytes and abnormal hepatic transaminases; the diagnosis can be made by isolation of cytomegalovirus (CMV) in urine or peripheral blood leukocytes, by serology, or by PCR on blood.
  • Neonatal infection may be diagnosed by demonstration of CMV in urine; PCR testing of amniotic fluid is not yet standardized.

General Considerations

CMV is thought to be the most common congenital infection in humans. Rates of seropositivity in the adult population range from 35% to close to 100%, depending on the population studied. Approximately 1% of all live-birth infants in the United States are infected by CMV. 90% of infants with infection will be asymptomatic at birth, but manifestations of infection such as sensorineural hearing loss, chorioretinitis, mental retardation, and neurologic deficits will develop later in 10–20% of infants. More severe symptoms will occur in infants who are symptomatic at birth.

CMV differs from other causes of congenital infection in that mothers with both primary infection and a history of infection can transmit the virus to the fetus. Children born to mothers with a history of infection prior to conception are less likely to be symptomatic at birth, and the presence of maternal antibody may help prevent the serious sequelae of congenital infection. Transmission occurs by the passage of virus across the placenta or by ascending infection from the cervix. It can also occur during the neonate's passage through the birth canal, but this will not cause congenital infection.

Clinical Findings

  1. Signs and Symptoms.Maternal infection may be asymptomatic, subclinical, or similar to mononucleosis. Congenital infection can be asymptomatic initially, although in 10–20% of asymptomatic infants neurologic deficits such as sensorineural hearing loss will develop later, usually within the first 2 years of life. Symptomatic cytomegalic inclusion disease develops in 6–19% of infants infected in utero. This is characterized by hepatosplenomegaly, jaundice, thrombocytopenia, chorioretinitis, cerebral calcifications, and microcephaly. Interstitial pneumonitis may also develop. The mortality rate of infants who are symptomatic at birth is approximately 29%. Perinatal infection can occur, in which the neonate acquires the virus from the mother who is seropositive, during passage through the birth canal. Most infections occurring in this manner are subclinical, although there have been some cases of interstitial pneumonitis developing in these infants, especially in premature infants.
  2. Laboratory Findings.The mother may demonstrate seroconversion on serologic testing. Hepatic transaminase levels may be abnormal, and atypical leukocytes may be present. Virus can be isolated from the urine and peripheral blood leukocytes, but urine positivity may persist for months to years and does not establish acute infection. CMV-specific immunoglobulin M (IgM) can be detected in cord blood in approximately 60% of infected infants, but false-positive reactions also occur. Polymerase chain reaction (PCR) testing may be used to detect virus in amniotic fluid, but the technique has not yet been standardized.

Treatment

There is no approved treatment available for congenital infection. Viruria can be suppressed with adenine arabinoside, but rebounds as soon as therapy is stopped. Ganciclovir therapy is being studied in research protocols.

Prognosis

As stated earlier, neurologic deficits will develop in 10–20% of asymptomatic infants within the first 2 years of life. Of infants infected in utero, cytomegalic inclusion disease will develop in between 6% and 19%, with a mortality rate approaching 30%.

Prevention & Control

Prevention is difficult owing to the number of subclinical infections. There are experimental live attenuated vaccines under investigation in immunocompromised adults. Routine screening of pregnant women is not recommended at this time.

RUBELLA IN PREGNANCY

Essentials of Diagnosis

  • Mild maculopapular rash, generalized lymphadenopathy, and transient arthritis in mothers.
  • Cataracts, heart abnormalities, deafness, microcephaly, mental retardation, hepatosplenomegaly, hemolytic anemia, pneumonia, and striate radiolucencies in the bones. Extensive permanent sequelae in infants.
  • Serologic diagnosis in mother and infant; virus isolation can be accomplished, but may take several weeks.

General Considerations

There are a notable number of women of child-bearing age who are susceptible to rubella, and thus their infants are at risk for congenital rubella, a disease with many serious and permanent sequelae. Rubella in pregnant women is similar to that in nonpregnant women; the likelihood of subclinical infection is similar as well. Spontaneous abortion occurs in 4–9% and stillbirths in 2–3% of pregnancies complicated by rubella infection.

The sequelae of fetal infection are thought to be caused by the effect of rubella virus on fetal cells, that is, prevention of cells from multiplying properly, resulting in fewer cells and smaller organs.

Transmission of infection is greatest in the first trimester, with rates up to 80% for the first 12 weeks of pregnancy, 54% during the 13th and 14th weeks, and 25% during the second trimester. Fetal infection occurs with both symptomatic and asymptomatic maternal infection, although the risk of fetal anomalies is greatest when infection occurs during the first trimester.

Clinical Findings

  1. Signs and Symptoms.As already stated, maternal infection is characterized by a mild maculopapular rash, generalized lymphadenopathy, and transient arthritis. Maternal infection may also be subclinical.

Congenital rubella infection is characterized by hepatosplenomegaly, jaundice, hemolytic anemia, pneumonia, and striated radiolucencies in the bones. More permanent sequelae include microcephaly, sensorineural hearing loss, congenital heart abnormalities such as patent ductus arteriosus, cataracts, glaucoma, microophthalmia, and mental retardation. Delayed manifestations include endocrinopathies, such vascular abnormalities as arteriosclerosis and hypertension, and panencephalitis.

  1. Laboratory Findings.Viral isolation may take up to 6 weeks, so serologies are often relied upon to make the diagnosis. Neutralization and hemagglutination (HI) antibodies appear soon after onset of the rash and persist indefinitely. Seroconversion of the HI antibodies is diagnostic. Complement fixation (CF) antibodies appear several days after onset of the rash and disappear after 10–20 years in 50% of individuals. CF antibody titers may be helpful in individuals in whom the HI antibody titer remains stable. A rubella immunoglobulin M (IgM) assay may also help to define recent infection. In infants, diagnosis is made by isolation of the virus from various body fluids (positive in approximately 90% of infected infants) or by serology. Persistence of immunoglobulin G (IgG) antibody over time supports the diagnosis of congenital rubella, as titers of passively transmitted maternal antibody begin to disappear after about 1 month.

Treatment

There is no treatment for infected infants or mothers, other than supportive care.

Prognosis

The overall mortality for infants is 5–35%.

Prevention & Control

Currently a live attenuated vaccine is available, which induces immunity in approximately 95% of recipients. Although the risk of transmission of vaccine virus to the fetus is small, vaccination is contraindicated in known pregnancy. If a woman receives vaccine and then discovers that she is pregnant, she should be counseled with respect to the risks of vaccine to the fetus, and termination of the pregnancy may be considered.

All unvaccinated women of childbearing age should have their rubella antibody titers evaluated, because clinical history of previous rubella infection is unreliable. If a woman is seronegative and not pregnant, she should receive the vaccine.

VARICELLA INFECTION DURING PREGNANCY

Essentials of Diagnosis

  • Typical vesicular rash in the mother.
  • Infants may have characteristic vesicular rash, disseminated disease, or congenital anomalies or might be asymptomatic at birth but have an episode of zoster many years later.
  • Maternal varicella infection diagnosed clinically by examination of direct fluorescent antibody (DFA) preparations of infected cells from lesions or by serology.
  • Neonatal infection diagnosed serologically.

General Considerations

The incidence of varicella infection as a complication in pregnancy is estimated to be about 0.01–0.7 cases/1000 pregnancies. Varicella infection in adults is more severe than in children. Pregnant women may have a more severe form of the disease than nonpregnant women, with a 41% mortality among infected women in the former group. Varicella-zoster virus (VZV) infection can have several effects on a pregnant woman and her fetus. Intrauterine infection with VZV can occur, rarely leading to congenital anomalies. Postnatal disease can also occur in newborns, ranging from a benign course characterized by typical lesions to a fatal disseminated form of disease. Zoster can also appear in the infant or child years after birth, even when the newborn subject was asymptomatic at birth. Such congenital anomalies as hypoplastic limbs and cutaneous scarring seen with VZV are thought to be caused by viral damage to developing tissues in a dermatomal distribution.

Clinical Findings

  1. Signs and Symptoms.Maternal disease is relatively easy to diagnose, as the mother will have the characteristic rash. Maternal infection at any stage of pregnancy can result in fetal growth retardation, aplasia of a single limb, cutaneous lesions, neurologic damage such as hearing loss, psychomotor retardation, microophthalmia, chorioretinitis, and cataracts. Neonatal disease ranges from benign cutaneous rash to disseminated disease with pneumonitis.
  2. Laboratory Findings.Maternal infection can be diagnosed clinically, with confirmation by immunofluorescence of scrapings from a lesion. Seroconversion is also diagnostic. In the newborn, immunofluorescence or culturing of a lesion provides the diagnosis, as does persistence of antibody long after maternal antibodies are expected to disappear.

Prognosis

Although the actual rate of fetal transmission is unknown, 5–7% of pregnancies complicated by VZV infection in the first trimester result in a newborn with congenital malformations. In pregnancies complicated by infection within 3 weeks of delivery, 17–24% of babies are infected at birth or shortly thereafter. Infants born to mothers with current varicella infection are at greatest risk of the development of disseminated disease, which is associated with a mortality rate of 30%.

Treatment & Prevention

Pregnant, nonimmune women who have been exposed to the virus can be given varicella immune globulin within 96 hours of the exposure. However, there is no evidence that this practice will prevent viremia and, thus, fetal infection. Acyclovir should be given to the infected mother. Infants should receive varicella immune globulin if the mother develops disease 5 days before delivery or 2 days after delivery. Infants with disseminated disease should receive antiviral therapy.

HERPES SIMPLEX VIRUS INFECTIONS IN PREGNANCY

Essentials of Diagnosis

  • Characteristic lesions in mothers.
  • Vesicular rash, keratoconjunctivitis, encephalitis, and disseminated disease in neonates.
  • History of herpes infection in mothers or their partners and positive results on viral cultures, immunofluorescence, or polymerase chain reaction (PCR) tests of cerebrospinal fluid (CSF).

General Considerations

Neonatal herpes simplex virus (HSV) infection is estimated to occur in 2–7 infants/10,000 live births. Most cases are acquired during labor and delivery and are caused by HSV-2. Risk factors for neonatal HSV infection include active genital lesions at delivery, primary infection (greater risk than with recurrence), a history of genital herpes in mothers or their partners, delivery through an infected birth canal, delivery by cesarean section 6 or more hours after rupture of membranes, and instrument-assisted delivery. Premature infants are more likely than term infants to be infected. It is estimated that 0.1–0.39% of all pregnant women shed HSV at delivery. Cultures of the mother's genital tract collected days or weeks before delivery do not predict an infant's chances of exposure at the time of delivery.

Clinical Findings

  1. Signs and Symptoms.The mother may have active genital lesions or be asymptomatic. Of infants affected by HSV infection, 40% have mothers do not recall a history of HSV infection. An infant will commonly show signs of infection at 1–3 weeks of age. HSV infection can result in skin disease with the characteristic vesicular lesions, keratoconjunctivitis and chorioretinitis, encephalitis, and disseminated disease.
  2. Laboratory Findings.Most useful for diagnosis is isolation of the virus from skin lesions from the mother or infant. Immunofluorescent smears of cells from lesions are more rapid than culturing. DFA preparations of infected cells from lesions may provide a diagnosis relatively quickly. Serology is generally not useful, as it is often difficult to differentiate acute from past infection with the virus as well as whether the infection is due to HSV-1 or -2. Polymerase chain reaction (PCR) tests on cervical fluid may be more sensitive in detecting asymptomatic viral shedding in women.

Treatment & Prevention

The mother may be treated with oral acyclovir if she has active lesions. The neonate needs treatment with acyclovir intravenously. Predicting shedding of virus at the time of delivery is difficult. The American College of Obstetricians and Gynecologists (ACOG) recommends that cultures be taken to confirm the diagnosis of HSV when a pregnant woman has typical lesions. If there are no visible lesions at the time of delivery, vaginal delivery is acceptable. Weekly surveillance cultures of a woman with a history of HSV are not necessary. Amniocentesis in an attempt to confirm fetal infection is not recommended. Cesarean delivery should be performed when there are active lesions near the time of labor, when membranes are ruptured for less than 6 hours, or when there are prodromal symptoms of a recurrence.

Prognosis

It has been estimated that for a woman experiencing a primary episode of genital herpes at the time of delivery, there is a 50% risk of her neonate acquiring neonatal herpes, whereas for a woman who has a recurrence of genital herpes at the time of delivery, the risk is 3%.

HUMAN PAPILLOMAVIRUS IN PREGNANCY

Essentials of Diagnosis

  • Condylomata acuminata in mothers.
  • Laryngeal papillomas in children born to infected mothers.
  • Polymerase chain reaction (PCR) analysis of lesions in mother and child to make rapid diagnosis.

General Considerations

Human papillomavirus (HPV) is the causative agent of genital warts, or condylomata acuminata. Various subtypes are more likely to cause malignant transformation of cervical cells, leading to cervical intraepithelial neoplasia and cervical cancer. In children, the virus can cause laryngeal papillomas, with exposure to the virus presumably occurring during passage through the birth canal. However, the virus can be transmitted to the child even when the mother has subclinical infection and no apparent lesions; as well, infants delivered by cesarean section have virus DNA in their nasopharynx, suggesting that there may be transplacental transmission of virus. The number of children who are born to infected mothers and later develop laryngeal papillomas is not known.

Clinical Findings

  1. Signs and Symptoms.Infection in the pregnant woman may be notable for the great increase in size and number of genital lesions. The lesions may grow so large that vaginal delivery is impossible, necessitating cesarean delivery. The infant may be asymptomatic at birth, but laryngeal papillomas may develop within the first 2–5 years of life. These papillomas are located on the vocal cords and epiglottis but can involve the whole larynx and tracheobronchial tree.
  2. Laboratory Findings.In the mother, cervical scrapings, biopsies of lesions, or scrapings from the lesions will display typical HPV-induced histologic or cytologic changes. PCR can detect viral DNA rapidly. Biopsies or scrapings from the child's lesions can also be tested by PCR.

Treatment

Lesions are treated if they cause discomfort or when it is anticipated that they will interfere with delivery. Trichloroacetic acid (50% or 80%) in 70% ethanol applied to the lesions three times a week or once a week is inexpensive and safe for the mother and fetus. Cryotherapy and laser ablation are also safe and well-tolerated in pregnant women. Podophyllin, 5-fluorouracil cream, and interferon therapy should not be administered to pregnant women.

Currently, the American College of Obstetricians and Gynecologists does not recommend routine cesarean delivery in women who have HPV infection.

Prognosis, Prevention, & Control

In the mother, genital warts usually diminish in size after delivery. In the child, surgery may be required to remove laryngeal papillomas. One study found that 32% of children born to mothers with genital papillomavirus had positive oral scrapings for papillomavirus DNA. Prevention consists of screening high-risk women aggressively for HPV.

MEASLES, MUMPS, & PARVOVIRUS INFECTION IN PREGNANCY

Measles infection complicates 6–40/100,000 pregnancies. There appears to be an increased risk of stillbirth, abortion, prematurity, and low birth weight in infants born to mothers who had infection while pregnant. There is no recognizable pattern of congenital anomalies with measles infection. Pregnant, nonimmune women who are exposed to the virus should be given immune serum globulin (0.25 mg/kg) within 6 days of the exposure. Such prophylaxis may modify maternal infection, but effects on fetal infection are unknown. Vaccination against measles is contraindicated within 3 months of conception because of the possibility of transmitting vaccine virus to the fetus.

Mumps infection occurs less frequently than measles during pregnancy, with an incidence of 0.8–10 cases/100,000 pregnancies. Mumps in pregnant women is similar to mumps in nonpregnant women. Transplacental infection does occur, but it is very rare. Virus has been isolated from breast milk, so transmission of virus from lactating women to their infants is possible. Virus can also be isolated from placental and fetal tissues, and there is a possible association between mumps during pregnancy and fetal endocardial fibroelastosis. Perinatal mumps can occur as well and may be complicated by pneumonia. Maternal infection may increase the risk of fetal loss. There is no effective treatment for an infected mother or child, other than supportive care. Prevention is best accomplished by ensuring that all women of childbearing age have been vaccinated against mumps.

Parvovirus (see Chapter 42) causes erythema infectiosum in childhood and aplastic crises in patients with hemolytic anemia. It is an uncommon infection during pregnancy (< 1% of all pregnancies), and an uncommon cause of stillbirths in women who have been exposed to the virus. Fetal hydrops and fetal death have been linked to some cases of parvovirus B19 infection during pregnancy. A large prospective study found that 17% of pregnant women who became immunoglobulin M (IgM)–positive in the first trimester suffered fetal losses, whereas 6% of women who became IgM-positive during the third trimester suffered fetal losses. If a pregnant woman has an illness compatible with parvovirus B19 infection, parvovirus antigen or DNA may be detectable in serum as may specific IgM antibodies. The fetus should be monitored by ultrasonography and maternal serum alpha-fetoprotein (AFP) levels. Elevated AFP levels have been detected 6 weeks before fetal death and 4 weeks before anomalies are noted on ultrasonography.

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Postpartum Endometritis

Hemsell D: Prophylactic antibiotics in gynecologic and obstetric surgery. Rev Infect Dis 1991;13(10):S821.

Hiller SL et al: Role of bacterial vaginosis-associated microorganisms in endometritis. Am J Obstet Gynecol 1996;175:435–51.

Hoyme UB et al: The microbiology and treatment of late postpartum endometritis. Obstet Gynecol 1986; 68:226.

Mead PB: Infections of the female pelvis. In Mandell GL, Bennett JE, Dolin R (editors): Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. Churchill Livingstone, 1995.

Newton ER et al: A clinical and microbiologic analysis of risk factors for puerperal endometritis. Obstet Gynecol 1990;75:402.

Puerperal Ovarian Vein Thrombophlebitis (POVT)

Mead PB: Infections of the female pelvis. In Mandell GL, Bennett JE, Dolin R (editors): Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. Churchill Livingstone, 1995.

Duff P, Gibbs RS: Pelvic vein thrombophlebitis: diagnostic dilemma and therapeutic challenge. Obstet Gynecol Surv 1983;38:365.

Episiotomy Infections

Mead PB: Infections of the female pelvis. In Mandell GL, Bennett JE, Dolin R (editors): Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. Churchill Livingstone, 1995.

Septic Abortion

Stubblefield PG, Grimes DA: Septic abortion. N Engl J Med 1994;331:310.

Group B Streptococcus (GBS)

American College of Obstetricians and Gynecologists: Prevention of early-onset group B streptococcus in newborns. Committee on Obstetric Practice 1996; No. 173.

Boyer KW, Gotoff SP: Prevention of early onset neonatal group B streptococcal disease with selective intrapartum chemoprophylaxis. N Engl J Med 1986;314: 1995.

Centers for Disease Control: Prevention of neonatal group B streptococcal disease: A public health perspective. MMWR 1996;45:RR-7:1.

Clark P et al: Effectiveness of the ACOG guidelines in reducing the incidence of neonatal group B streptococcal sepsis. Am J Obstet Gynecol 1996;174:405.

Gibbs RS et al: Neonatal group B streptococcal sepsis during 2 years of a universal screening program. Obstet Gynecol 1994;84:496.

Mercer BM et al: Prenatal screening for group B streptococcus I: Impact of antepartum screening on antenatal prophylaxis and intrapartum care. Am J Obstet Gynecol 1995;173:837.

Noya FJ, Baker CJ: Prevention of group B streptococcal infection. Infect Dis Clin North Am 1992;6:41.

Pylipow M et al: Selective intrapartum prophylaxis for group B streptococcus colonization: Management and outcome of newborns. Pediatrics 1994;93:631.

Rouse DJ et al: Strategies for the prevention of early-onset neonatal group B streptococcal sepsis: A decision analysis. Obstet Gynecol 1994;83:483.

Towers C et al: Are the ACOG risk factors for GBS prophylaxis practical? Am J Obstet Gynecol 1996;174: 406.

Syphilis in Pregnancy

Coles FB et al: Congenital syphilis surveillance in upstate New York, 1989–1992: Implications for prevention and clinical management. J Infect Dis 1995; 171:732.

Greenwood AM et al: Treponemal infection and the outcome of pregnancy in a rural area of the Gambia, West Africa. J Infect Dis 1992;166:842.

McFarlin BL et al: Epidemic syphilis: Maternal factors associated with congenital infection. Am J Obstet Gynecol 1994;170:535.

Rawstron SA et al: Maternal and congenital syphilis in Brooklyn, NY: Epidemiology, transmission, and diagnosis. Am J Dis Child 1993;147:727.

Toxoplasmosis in Pregnancy

Couvreur J, Desmonts G: Toxoplasmosis, pp 112–142. In MacLeod C (editor): Parasitic infections in pregnancy and the newborn. Oxford University Press, 1988.

Hohlfield P et al: Prenatal diagnosis of congenital toxoplasmosis with a polymerase-chain-reaction test on amniotic fluid. N Engl J Med 1994;331:695.

Hunter K et al: Prenatal screening of pregnant women for infections caused by cytomegalovirus, Epstein-Barr virus, herpes virus, rubella, and Toxoplasma gondii. Am J Obstet Gynecol 1983;145:269.

Sever J et al: Toxoplasmosis: Maternal and pediatric findings in 23,000 pregnancies. Pediatrics 1988;82: 181.

Shay-Pederson B, Lorentzen-Styr A: Uterine toxoplasma infections and repeated abortion. Am J Obstet Gynecol 1977;138:357.

Cytomegalovirus in Pregnancy

Alford C, Bvritt W: Cytomegalovirus, pp 1981–2010. In Fields BN, et al (editors): Virology, 2nd ed. Raven Press, 1990.

Fowler KB et al: The outcome of congenital cytomegalovirus in relation to maternal antibody status. N Engl J Med 1992;326:663.

Varicella Infection During Pregnancy

Brunell PA: Varicella in pregnancy, the fetus, and the newborn: Problems in management. J Infect Dis 1992;166(Suppl 1):S42.

Enderes G et al: Consequences of varicella and herpes zoster in pregnancy: Prospective study of 1739 cases. Lancet 1994;343:1547.

Katz VIL et al: Varicella during pregnancy—maternal and fetal effects. West J Med 1995;163:446.

Rouse DJ et al: Management of the presumed susceptible varicella (chickenpox)-exposed gravia: A cost-effectiveness/cost-benefit analysis. Obstet Gynecol 1996;87:932.

Herpes Simplex Virus Infections In Pregnancy

American College of Obstetricians and Gynecologists: Perinatal herpes simplex virus infections. Technical Bulletin No. 122, 1988.

Arvin AM et al: Failure of antepartum maternal cultures to predict the infant's risk of exposure to herpes simplex virus at delivery. N Engl J Med 1986;315:796.

Boggess KA et al: Herpes simplex type 2 detection by culture and polymerase chain reaction and relationship to genital symptoms and cervical antibody status during the third trimester of pregnancy. Am J Obstet Gynecol 1997;176:443.

Brown ZA et al: Neonatal herpes simplex virus infection in relation to asymptomatic maternal infection at the time of labor. N Engl J Med 1991;324:1247.

Human Papillomavirus In Pregnancy

American College of Obstetricians and Gynecologists: Genital human papillomavirus infections. Technical Bulletin No. 193, June 1994.

Fife KH et al: Cancer-associated human papillomavirus types are selectively increased in the cervix of women in the first trimester of pregnancy. Am J Obstet Gynecol 1996;174:1487.

Puranen M et al: Vertical transmission of human papillomavirus from infected mothers to their newborn babies and persistence of the virus in childhood. Am J Obstet Gynecol 1996;174:694.

Puranen M et al: Exposure of an infant to cervical human papillomavirus infection of the mother is common. Am J Obstet Gynecol 1997;176:1039.

Measles, Mumps, & Parvovirus Infection In Pregnancy

Eberhart-Philips et al: Measles in pregnancy: A descriptive study of 58 cases. Obstet Gynecol 1993;82:797.

Public Health Laboratory Service Working Party on Fifth Disease: Prospective study of human parvovirus (B19) infection during pregnancy. Br Med J 1990; 300:1166.

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General

Burrow GN et al (editors): Medical Complications during Pregnancy. Saunders, 1995.

Centers for Disease Control and Prevention: Guidelines for treatment of sexually transmitted diseases. MMWR 1998;47(No. RR-1).

Cunningham FG et al (editors): Williams' Obstetrics. Appleton & Lange, 1997.

Mandell GL et al (editors): Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. Churchill Livingstone, 1995.

Sanford JP, et al (editors): The Sanford Guide to Antimicrobial Therapy 1997. Antimicrobial Therapy, Inc. 1997.