Clinical Review

INFECTIOUS DISEASES

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CMV vaccine…Outpatient PID therapy…C-section healing in the obese…2 useful antibiotics now unavailable


 

References

For the 2006 Update, I have chosen to focus on 3 important new clinical reports that stand to improve patient care, and another development that necessitates a change in how we treat gonorrhea in pregnant women:

CMV vaccine. A new immunologic agent for the treatment and prevention of congenital cytomegalovirus (CMV) infection is extremely promising. Until now, no consistently effective therapy for this serious congenital infection has been identified.

  • Recommended hygiene measures to prevent transmission—Page 64

Outpatient treatment of PID. Relatively inexpensive outpatient therapy for mild to moderately severe pelvic inflammatory disease was demonstrated to be equal to inpatient therapy in efficacy and safety.

  • Whom to hospitalize—Page 68

Wound complications after cesarean delivery in the obese were reduced by use of subcutaneous closure and avoidance of surgical drains.

  • Recommended technique—Page 70

2 antibiotics with unique application in the treatment of uncomplicated gonococcal infections in pregnant women—cefixime and spectinomycin—were recently withdrawn from the market. This unfortunate development is a special dilemma in pregnant women with allergy to beta-lactams.

  • Alternative regimens, using other antibiotics—Page 75

A promising therapy for congenital CMV

For now, emphasize prevention

Nigro G, Adler SP, LaTorre R, Best AM. Passive immunization during pregnancy for congenital cytomegalovirus infection. N Engl J Med. 2005;353:1350–1362.

  • Although anti-cytomegalovirus hyperimmune globulin appears to have great promise for prevention and treatment of congenital CMV infection, I propose that obstetricians avoid a rush to judgment and maintain their focus on simple measures to prevent horizontal transmission of CMV

Summary

Nigro and colleagues present a provocative report of a promising new treatment for congenital cytomegalovirus (CMV) infection. Their prospective cohort study at 8 Italian medical centers involved 157 pregnant women with confirmed primary CMV infection: 148 women were asymptomatic and were identified by routine serologic screening; 8 had symptomatic infections and 1 had ultrasound findings consistent with congenital CMV infection.

CMV was detected in the amniotic fluid of 45 women who had a primary infection more than 6 weeks before enrollment, and 31 of these women agreed to receive CMV-specific hyperimmune globulin (200 units per kilogram of maternal body weight). Nine of the 31 women received 1 or 2 additional infusions into either the amniotic fluid or umbilical cord because of persistent fetal abnormalities on ultrasound.

  • Only 1 of the 31 treated women delivered an infected infant (adjusted odds ratio, 0.02; P<.001).
  • In contrast, of the 14 women who declined treatment, 7 had infants who were symptomatically infected at birth.

There were 84 additional women who did not have an amniocentesis because their infection occurred within 6 weeks of enrollment, their gestational age was less than 20 weeks, or they declined the procedure. Of these, 37 agreed to treatment with 100 U of hyperimmune globulin per kilogram of maternal weight every month until delivery.

  • 6 of these treated women delivered infected infants.
  • In contrast, 19 of the untreated women (adjusted odds ratio 0.32; P=.04) delivered infected infants.

No adverse effects of hyperimmune globulin were noted in either treatment group.

Commentary

This study is remarkable because, until now, no consistently effective therapy for this serious congenital infection has been available. However, before we fully embrace the findings, 3 caveats should be considered.1

  1. Although the study was prospective, it was neither randomized nor controlled. The lack of strict randomization resulted in a curious blend of 2 cohorts—a treatment group and a prevention group. The dosage regimens were different both within and between the 2 groups.
  2. There are biological reasons to question the remarkable success rates reported by the authors. For example, administration of anti-HIV hyperimmune globulin has not protected neonates against perinatal transmission of HIV.2 Moreover, the presence of naturally acquired antibody against CMV does not fully protect a mother or her fetus against reactivation and subsequent perinatal transmission of CMV infection.1 This latter observation is particularly important in assessing the authors’ observations that major abnormalities identified by ultrasound, such as ascites, ventriculomegaly, intracerebral and intraabdominal echodensities, and intrauterine growth restriction apparently resolved completely in 14 fetuses after maternal treatment.
  3. The study did not address the financial and logistic issues of screening large obstetric populations for CMV infection, triaging patients with inevitable false-positive test results, performing targeted sonography and amniocentesis in affected women, and then treating at-risk women with hyperimmune globulin.

Recommendations

Hyperimmune globulin appears to be very safe and to have great promise for treatment and prevention of congenital CMV infection. However, additional investigations are needed to delineate the appropriate dose, method of administration, and timing of immunoprophylaxis and to define its precise level of effectiveness.

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