Cytomegalovirus intrauterine infection: Pharmacokinetics of ...

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SMFM Abstracts S57 173

CYTOMEGALOVIRUS INTRAUTERINE INFECTION: PHARMACOKINETICS OF VALACICLOVIR ADMINISTRATION TO THE MOTHER AND CHANGES IN DNA VIRAL LOAD IN AMNIOTIC FLUID AND FETAL BLOOD FRANC¸OIS JACQUEMARD1, MASAMI YAMAMOTO2, OLIVIER PICONE2, JEAN-MARC COSTA3, S. ROMAND3, EVELYNE JACZ-AIGRAN4, FERDINAND DAFFOS1, YVES VILLE5, 1Institute de Puericulture de Paris, Service de Medicine Foetale, Paris, France, 2Universite Paris Ouest SQY-V CHI Poissy St Germain en Laye, Obstetrics and Gynecology Service, Poissy, France, 3American Hospital of Paris, Service de Biologie Mole´culaire Marcel Dassault, Neuilly sur Seine, France, 4Hopital Robert Debre, Paris, France, 5CHI Poissy-St Germain, Poissy, France OBJECTIVE: Cytomegalovirus infection is the main cause of infection-related congenital handicap. The use of valaciclovir is not associated with maternal or fetal toxicity. Aim of the study: To treat symptomatic infected fetuses with valaciclovir and to study drug pharmacokinetics and changes in viral load in maternal and fetal compartments. STUDY DESIGN: Valaciclovir was given orally to mothers of symptomatic infected fetuses, 8 g/day up to delivery. Fetal infection was diagnosed by amniocentesis and viral genome amplification by PCR. Fetal symptoms consisted of cytomegalovirus-related ultrasound abnormalities and / or thrombocytopenia and hepatitis in fetal blood. RESULTS: 17 women were treated for 6 (1-12) weeks without any side effect. Ten women delivered of healthy neonates. Two neonates presented severe hearing loss. Termination of pregnancy was requested in 6 cases with progressive fetal affection One such case had intrauterine death. Good placental transfer of valaciclovir and similar concentrations above IC50 were achieved in maternal and fetal blood but were higher in amniotic fluid. Viral load decreased in fetal blood from 6 ! 104 to 1.5 ! 103 cp/mL (P = .006). Viral load was not correlated with outcome in the amniotic fluid but decreased in fetal blood in 9 of 10 cases with a good outcome, and increased in 3 of 6 cases with a poor outcome. Valaciclovir concentrations were similar in maternal and fetal blood (3.95 mg/mL and 3.65 mg/mL), but higher in amniotic fluid (12 mg/mL). No correlation was found between viral load and duration of treatment nor with valaciclovir concentrations. CONCLUSION: Intrauterine treatment of fetal CMV infection appears achievable with adequate drug concentrations in the fetal compartment with maternal oral administration of valaciclovir. However its efficacy should be assessed in a randomised controlled study. Viral load in fetal blood is a better prognostic factor than that in the amniotic fluid.

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HEPATITIS C QUANTITATIVE VIRAL LOAD AS A PREDICTOR OF PREGNANCY OUTCOME VANESSA LAIBL1, JEANNE SHEFFIELD1, SCOTT ROBERTS1, DONALD MCINTIRE1, GEORGE WENDEL JR1, 1University of Texas Southwestern Medical Center, Obstetrics and Gynecology, Dallas, Texas OBJECTIVE: Studies have reported the effect of pregnancy on hepatitis C; however, few have reported the effect of hepatitis C on pregnancy. We examined the effect of hepatitis C quantitative viral load on obstetric complications in infected women. STUDY DESIGN: Retrospective review of all hepatitis C-infected pregnant patients in whom a quantitative viral load was measured as part of their prenatal care between January 1, 2000 and June 30, 2004. Patients were grouped based on viral load, and obstetric outcomes were reviewed. Complications of interest included cesarean delivery, preeclampsia or eclampsia, abruption, preterm birth, presence of meconium, and fetal distress. RESULTS: Hepatitis C quantitative viral loads and obstetrical outcomes were available in 96 patients with 101 deliveries. Patients were grouped into nondetectable viral load (n = 28), viral load 1,000-500,000 copies/ml (n = 48), and viral load >500,000 copies/ml (n = 25). The three groups were not significantly different in terms of race, age, parity, or mode of delivery. Twenty-six percent of patients were nulliparous. Six percent of patients were infected with hepatitis B, and 7% with HIV. Overall, there were 38 cesarean deliveries. Indications for cesarean deliveries were previous cesarean delivery (53%), dystocia/failure to progress (23%), malpresentation (8%), fetal distress (8%), and other (8%). None of the HIV-infected patients had a cesarean delivery because of their HIV status. There was no significant difference between the three groups in incidence of preeclampsia (3%), abruption (1%), preterm birth (6%), meconium stained amniotic fluid (19%), or fetal distress (3%). None of the 96 patients developed chorioamnionitis or eclampsia. CONCLUSION: Increasing quantitative viral loads in hepatitis C patients were not associated with excess obstetrical complications. The cesarean delivery rate was higher than expected; however the rate was not significantly different among the three groups. Rates of obstetrical complications did not differ from those expected in our general obstetrical population.

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CLINICAL PRESENTATION OF COMMUNITY-ACQUIRED METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS IN PREGNANCY VANESSA LAIBL1, JEANNE SHEFFIELD1, SCOTT ROBERTS1, GEORGE WENDEL JR1, 1University of Texas Southwestern Medical Center, Obstetrics and Gynecology, Dallas, Texas OBJECTIVE: Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) is becoming an increasingly common problem. The objective of this study is to review the presentation and management of community-acquired MRSA in pregnant women. STUDY DESIGN: Retrospective chart review of pregnant patients who were diagnosed with MRSA between January 1, 2000 and June 30, 2004. Data collected included demographic characteristics, clinical presentation, culture results, and pathogen susceptibilities. RESULTS: Forty-four charts were available for review. There were 2 cases in 2000, 4 in 2001, 10 in 2002, 21 in 2003, and 7 through June of 2004. The mean age of the patients at the time of culture was 26.2 G 6.7 years. Co morbid conditions included HIV/AIDS (20%), asthma (17%), and diabetes (10%). Mean gestational age at culture was 19.8 G 8.8 weeks; however 21% of cases occurred in the post partum period. Skin and soft tissue infections were the most common source accounting for 95% of cases. The most common site for a lesion was the extremities (41%), followed by the vulva (20%), buttocks (20%), and breast(mastitis) (16%). Fifty-six percent of patients had recurrent episodes at multiple skin and soft tissue sites. Two patients (4%) had MRSA isolated in their urine. All MRSA isolates were sensitive to trimethoprim-sulfamethoxazole, vancomycin, and rifampin. Other antibiotics to which the isolates were susceptible included gentamycin (98%), levofloxacin (84%), ciprofloxacin (88%), and tetracycline (91%). CONCLUSION: Community-acquired MRSA is an emerging problem in our obstetric population. Most commonly, it presents as a skin/soft tissue infection that involves multiple sites. Local infections can be treated with oral trimethoprim-sulfamethoxazole, and invasive or severe infections may require intravenous vancomycin. Recurrent skin abscesses during pregnancy should raise prompt investigation for MRSA.

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MANAGEMENT OF GROUP B STREPTOCOCCUS IN PREGNANT WOMEN WITH PENICILLIN ALLERGY ELLIOT PHILIPSON1, DAVID LANG2, STEVEN GORDON3, JANET BURLINGAME1, STEPHEN EMERY1, MERCEDES ARROLIGA2, 1Cleveland Clinic Foundation, Obstetrics and Gynecology, Cleveland, Ohio, 2Cleveland Clinic Foundation, Pulmonary, Allergy, and Critical Care Medicine, Cleveland, Ohio, 3 Cleveland Clinic Foundation, Infectious Disease, Cleveland, Ohio OBJECTIVE: To determine whether Group B streptococcus (GBS) colonized pregnant women who report a history of ‘‘penicillin allergy’’ can safely undergo diagnostic evaluation to rule out or confirm the potential for IgE-mediated (allergic/anaphylactic) reaction to penicillin. If ruled out, pregnant women can receive penicillin with no increased risk of IgE-mediated reaction. STUDY DESIGN: From January 2003 to July 2004, all pregnant women with GBS positive vaginal/rectal culture and a history of ‘‘penicillin allergy’’ were referred to allergy/immunology for a detailed history and possible immediate hypersensitivity skin testing to penicillin determinants. Patients who experienced anaphylaxis were advised to continue avoiding penicillin and were not skin tested. Women without such a history underwent immediate hypersensitivity prick and intrademal testing using 2 full-stength penicillin antigens and positive and negative controls. The test results were considered positive if a wheal/flare reaction from either antigen was larger than the negative control after 15 minutes. If the test was negative, intrapartum antimicrobial prophylaxis with intravenous penicillin was administered. RESULTS: Of the 23 patients referred to the clinic with both GBS colonization and ‘‘penicillin allergy’’, 21 (91%) had negative skin testing to penicillin and received intrapartum penicillin for GBS prophylaxis without adverse reaction. In one patient penicillin skin testing was not performed due to a history of anaphylaxis from penicillin in the past. Skin testing was positive in another patient and intrapartum penicillin was not administered. CONCLUSION: These preliminary results indicate that most pregnant women reporting ‘‘penicillin allergy’’ can accomplish negative skin tests, and are able to safely receive intrapartum penicillin GBS prophylaxis. The advantages of penicillin use are the greater sensitivity to GBS, less tendency to develop resistant strains, and lower cost. Furthermore, young women may not need to continue avoiding penicillin for future antibiotic therapy.

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