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- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Maternal and neonataldirected Assessment - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - TO PROlOng PREgnAncy And REdUcE InFEcTIOn Condition
Pre-term, premature rupture of membranes (pPROM) occurs when the amniotic sac ruptures
before 37 weeks of gestation and prior to the onset of labor. It is a common cause of pre-
term birth and is present in about one third of cases in high-resource settings. Maternal and
neonatal infection is highly correlated with pPROM. The putative mechanism is that ascend-
ing bacteria from the genital tract trigger an inflammatory response in the decidua and fetal
membranes. This triggers the release of prostaglandins and other substances that soften the
cervix and initiate contractions leading to membrane rupture and preterm delivery. Preterm
infants have markedly higher morbidity and mortality rates.
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Mechanism of Action
Antibiotics may help in two ways. First, they treat the maternal/ neonatal infection, thereby re-
ducing infection-related morbidity. Second, by stopping the ascending bacteria, antibiotics may prolong pregnancy, al owing the fetus to further mature. The benefit of antibiotics is greatest fol owing pPROM <32wks gestation. Ampicil in, amoxicil in, and erythromycin are al commonly - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Maternal
used, either in an IV phase fol owed by an oral phase, or using an oral phase alone.
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Neonatal
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Current use in high resource settings
Stillbirth
Using an IV phase followed by an oral phase, caregivers often prescribe 2g ampicillin and 250mg erythromycin IV every 6 hrs for 48 hrs, followed by 250mg amoxicillin and 333mg erythromycin every 8 hrs for 5 days. Using an oral only program, caregivers often prescribe 250mg orally every 6 hrs for 10 days. System-atic review of existing randomized controlled studies does not suggest that oral only regimes are less effective.
Application in low resource settings
Antibiotics for pPROM are used infrequently in low resource set ings. Even in the absence of other interventions, including antenatal steroids,
surfactant, and ventilation, experts estimate that increasing use of antibiotics for pPROM from 0% to 100% could “prevent 4% of neonatal deaths
due to complications of prematurity and 8% of those due to infection.” At approximately $0.84 for the ful ten day oral course, this may represent an
especial y cost ef ective way to save lives.
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Prices are approximated. Actual pricing can, and will, vary by marketplace and market conditions. ChARACteRiStiCS Of RePReSentAtive PRODuCt (250 MG eRythROMyCin ORAlly) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - A patient aid documenting the correct use of the drug could be REQUIRED
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - ENVIRONMENT /
INFRASTRUCTURE
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Meta-analysis of 15 stud-ies of 4265 newborns sug- gests a neonatal mortality risk ratio of 0.90 Additional technology required for impact: Lives saved wil rise with the availability of other technologies used for complications of prematurity. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Sources: S Cousens et al. Antibiotics for pre-term pre-labour rupture of membranes: prevention of neonatal deaths due to complications of pre-term birth and infection. Int J Epidemiol. 2010 April; 39(suppl_1): i134–i143. Society of Obstetricians and Gynaecologists of Canada. SOGC Clinical Practice Guideline. Antibiotic Therapy in Preterm Premature Rupture of the Membranes. JOGC. September 2009. Management Sciences for Health (MSH). International Drug Price Indicator Guide 2009

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Department of General Surgical Science (Surgery I), Department of General Surgical Science The Department of General Surgical Science of the Gunma University Graduate School of Medicine was established in 1943. This year marks its 62nd anniversary. Six years have passed since I was appointed as replacement to Dr. Yukio Nagamachi at Gunma University in 1995. Throughout the years, I have

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