Neonatal Infections Janet Wong, M.D.Typical Syndrome of Congenital Infection Feature Comment SGA Causal relationship exist for rubella, CMV, toxoplasmosis Hepatosplenomegaly Jaundice Chorioretinitis Reflects microbial invasion and proliferation (not a defect in organogenesis) Eye defects Cardiac defects Cause by cell death or chromosooma damage Microcephaly Hydrocephaly Consequence of lesions from congennita infection rather than teratogenesis SGA (Small gestational age) or intrauterine growth retardatiio is characterized by jaundice, chorioretinitis, hepatosplenomegaly microcephaly, and hydrocephaly which are the direct result of the congenital infection and microbial invasion. By contrast, eye defects and cardiac defects are caused by cell death or chromosomal damage.Signs Common to Congenital Infectiion Purpura, jaundice, hepatosplenomegaly, pneumonitis, meningoencephalitis Common to rubella, CMV, HSV, Coxsackie B, T. gondii, T. pallidum Signs common to congenital infections include purpura, jaundice, hepatosplenomegaly, pneumonitis, meningoencephalitis. They are not all present in every patiien within congenital infection, but any of these features can be associated with various etiologies. They are common to rubella, cytomegalovirus, herpes simplex virus, Coxsackie B infections, Toxoplasma, and syphilis. Sign Rubella CMV Toxo Syphilis Hepatosplenomegaly + + + + Jaundice + + + + Exanthem --+ ++ Purpura/petechiae + + + + Hydrocephalus + + ++ -Microcephaly -++ + -Intracranial calcifications -++ ++ -Heart defects ++ ---Bone lesions ++ --+ Glaucoma ++ + -+ Chorioretinitis ++ + ++ + Cataracts ++ -+ -syphilis, whereas many of the others do not have an exanthem. None of them commonly have an exanthem, although some might have one. Another feature of diagnostic significance is the presence of intracranial calcifications which would suggest CMV. Keep in mind also toxoplasmosis, although a less common congenitta infection, also can give you intracranial infections, whereas if you had that finding of intracranial calcification, your patient and you were thinking about syphilis or rubella, you would not think that would be etiologically compatible. About 50% of childbearing-aged women are immune After household exposure, ~50% of susceptibles become infected Risk of presumed parvovirus-related fetal death from household exposure in first 20 weeks of pregnancy is 3-9% Risk alter 20 weeks of pregnancy is unknown; 3rd trimester infection may cause newborn anemia nonimmune and therefore susceptible. If a woman has a household exposure, we know that about 50% of the susceptibles in a household will become infected. There is a parvovirus B19 infection. So if a woman is pregnant and her two-year-old comes home with classic erythema infectiosum, she has about a 50% chance if she is susceptible of becomiin infected. The risk of presumed of parvovirus-related fetal death from household exposure in the first 20 weeks (early in pregnanncy is estimated at 3% to 9%. By contrast, after 20 weeks of gestation, the risk is absolutely unknown. It is estimated at less than one-percent. Third trimester infection may cause some newborn anemia, but usually this is not the hydrops fetalis type of scenario. Virus causes fetal anemia, heart failure and death (hydrops fetalis) Risk of fetal death after occupational exposure is low (<1%) No association with fetal anomaly secondary heart failure, and in utero death with the fetus that shows all the histopathologic features of hydrops fetalis. The risk of fetal death after occupational exposure is low. Most of the times the hospital’s employee has been shown to be seropositive and, therefore, not at risk.Rubella • Virus Culture: Nasopharynx is the most reliable site; conjunctivae, CSF or urine also are potential sites • Cord serum for rubella-specific IgM • CSF for rubella-specific • Persistence of rubella-specific IgG for 6-12 months CMV • Viral isolation: urine, saliva, tissues • Rapid viral diagnostic techniques Toxoplasmosis • Demonstration of IgM antibodies to toxoplasmosis in cord serum or infant serum is diagnostic; IgM antibodies in CSF supports the diagnosis in CNS infection • Double sandwich IgM-ELISA method is more sensitive than IgM-IFA • IgA antibodies to toxoplasmosis in infant • Demonstration of Toxoplasma antigens in CSF Parvovirus • Detection of IgM antibodies to parvovirus in infant serum • Parvovirus-specific PCR somebody being susceptible, you are going to have to do a serologic test. If the person has an immunity to parvovirus, then they are not susceptible then you do not have to deal with these pregnancy-related issues. If they are pregnant, depending on the time of gestation, you can at least counsel the patient, based on the gestation, about potential risk. The one thing to remember about parvovirus B19 is that you are not going to see fetal anomalies. So this virus is red cell specific. It causes anemia depending on the time of gestatiio and the anemia can cause spontaneous abortion or intrauterine death due to hydrops or presentation of a quite currently ill baby with hydrops fetalis.Mother with positive nontreponemal tests confirmed by a positive treponemal test and: Untreated or inadequately treated syphilis Treatment in pregnancy with non-penicillin regimen Lack of expected decrease in nontreponemal antibody titer after penicillin treatment Treatment <1 month before delivery Treatment not documented Insufficient follow-up to assess response and current status then the best way to make the clinical diagnosis is to get cord serum for specific IgG antibody. In patients who have meningoencephalitis, the spinal fluid actually may have IgM detectable antibodies too, so there are two specimens that can be serologically tested for IgM rubella specific antibody. You can culture this virus if you do have serology laboratory access, the nasopharyngeal secretions are the most reliable. IgG comes from the mother and is another serologic piece of information that is useful in congenitally infected babies. IgG persists for six to twelve months, and after that time you know that IgG is being made by the baby because passive antibody from the mother has gone away by that time. CMV. The cardinal way to make the diagnosis is isolation of this virus from a urine specimen. You also may isolate CMV from saliva or from tissues. There are a number of rapid viral diagnostic techniques for CMV. Urine cultures are fairly standard. The virus is not fastidious and the least expensive and easiest way to make a specific diagnosis is to grow CMV from the urine. In order to make the diagnosis of congenital CMV, you have to have access to your patient in the first two weeks of life because after that, acquiring CMV becomes a complicated interpretation problem.Syphilis Physical examination Quantitative nontreponemal serologic test CSF analysis for cells, protein, VDRL Antitreponemal IgM test Long bone x-rays Other clinically indicated tests (e.g., CBC, CXR) because the mother is going to have high levels of IgG that are transferred to the baby. We are looking for detection of toxoplasmosis, specific IgM antibodies in cord serum are tested. If the CNS is involved there is a serologic assay for cerebral spinal fluid that would support the diagnosis of CNS infection due to toxoplasmosis. The ELISA is much more sensitive than the indirect fluorescent antibody test as oppoose to the IFA. It is a more desirable method because it is more sensitive. The IgA antibody test is not a passively acquired antibody, so the baby has to be making it, and is very helpful as an adjuncctiv serologic piece of information in establishing the diagnosis of toxoplasmosis. Parvovirus is a virus that cannot be cultured. Serologic detecctio of IgM in the infant serum or cord serum is diagnostic. More and more places are now getting parvovirus specific PCR. Postnatally Acquired Nonbacterial Infection Sign HSV Enterovirus HBV HIV Hepatosplenomegaly + ++ ++ ++ Adenopathy -+ -++ Pneumonitis + + -++ Petechiae or purpura + + --Vesicles ++ ---Meningoencephalitis + + -+ Paralysis -++ --Myocarditis + ++ -+ Conjunctivitis or ++ + --Keratoconjunctivitis the RPR or VDRL. The first thing that happens is that we cannot say that she does not have a biologic false-positive, so we need to make sure, that if she has a treponemal test, that it is confirmed with a nontreponemal test. The MHATP is a common one and you need both of these to make a firm serologic diagnosis in the mother and the baby. For the definitive diagnosis of syphilis you have to have microscopic evidence of spirochetes, a dark field or direct fluorescent antibody specimen from some sort of mucopurulent secretions. The congenitally-infected patient, unless they have the typical exanthem, the pustule, where you can open them and they are teeming with spirochetes, before you treat the patient and do a dark field on that, all of our diagnoses of congenital syphilis is presumptive at best, and to make the presumptive diagnosis, you have to have a nontreponemal test that is confirmed with a treponemal antigen test. After the mother has confirmed both tests positive, she is untreated during her pregnancy. Inadequate treatment is a non-penicillin regimen. Obstetricians are told to desensitize the patient and treat with penicillin, but that does not always happen. Inadequate treatment would mean a non-penicillin drug or inappropriate dose, or inappropriate duration. Lack of expeccte decrease in VDRL or RPR after the patient has been treated, and usually what we are looking for is a four-fold or greater decrease. Treatment less than one month before delivery is considered inadequate. Treatment is considered inadequate if it can not be documented. Documented means that you have documented evidence. The patient saying that she was treated with penicillin is insufficient to document treatment. Insufficient follow-up to assess response is considdere inadequate. For example, you may not have access to a previous serology and you cannot assess her response to therapy unless you have previous results. So, once you have decided that the patient needs a diagnostti evaluation based on the mother’s situation, you do a physical examination, you do a quantitative nontreponemal serologic test. You do a spinal fluid through a lumbar punctuure You look at the cell count, protein and VDRL. Here we are in a situation where you really need spinal fluid that does not have contaminating blood, because if you had contaminattin blood it is difficult to interpret the protein and the cell count, it is virtually impossible to do a reliable VDRL when you have blood in the spinal fluid, you can send a VDRL, and if it is negative it is informative , but if it is positive you do not know whether that is from the blood or whether the patient has neurosyphilis. There are a lot of babies with completely normal cell counts and proteins who has positive VDRLs. Then there are some babies who have abnormal cell counts and abnormal proteein and negative VDRLs. They should all be treated for neurosyphilis. The IgM is a test that is not commercially available, but the CDC will do an IgM test for you. It is reliable for the diagnosiis Long bone x-rays are necessary because patients with congenital syphilis can have a completely normal physical examination and normal CSF analysis and have the osteolytic and periosteal elevation changes caused by congennita syphilis. This is clinically silent early, but still needs to be treated. For hepatitis B virus , babies who are more than a month ofNonbacterial Infections HSV • Specimens for culture from vesicle, mouth or throat, conjunctiva, blood and CSF yield virus in 1-3 days; DFA of vesicle scrapings or EIA of HSV antigens are specific but less sensitive Enterovirus • Specimens for viral isolation from throat and rectum and sites of clinical involvement (CSF, blood, biopsy material) HBV • Detection of HBsAg in infant's serum look to these, and so the timings areas at four to six months of age or somewhat older. Usually the viral agent is transmitted intrapartum. Typical findings at presentation, four to six months of age or slightly older, hepatomegaly, prominent adenopathy; the patient may have pneumonitis, and this is not an opportunistic infection, but usually the lymphoid intrastitial pneumonitis syndrome that we see typically with HIV. One comment about enteroviruses, is where as we see a disseminated fulminant presentation with hepatosplenomegaly, adenopathy, coagulopathy and often death. They may have very helpful clues to this presentation, with paralysis or myocarditis. That may help the clinician, but those are very ominous presentations because we do not have specific therapies for enteroviral disease and those patients typically do quite poorly. Diagnosis for HSV. For the patient that presents with the vesicle this is the most accessible way to have rapid viral diagnosis by culture virus. Without skin vesicles present, the mouth or throat, the conjunctiva are very good places to grow HSV virus. You also can also grow it from the blood, CSF. As I said, if you have a vesicle there is high titer of virus in those vesicles and virus grows rapidly, but you can also take direct scraping specimens and get the answer in minutes. There are quite specific -remember if your rapid test is negative, still wait for your culture because depending on the titer of virus these rapid tests may be negative. Enteroviruses. Throat and rectum are the sites that you usually grow the virus, but if you have a patient who has neonatal enteroviral infection and has meningoencephalitis, this CSF can yield the virus, or the amount of tissue, viral isolation is appropriate. Hepatitis B virus. You look for the presence of appropriate antigens to confirm the diagnosis in the infant’s serum. Premature Infants to Respiratory Infectiion Intrinsic/host Immaturity • Decreased IgG levels in direct proportion to gestation • Decreased opsonic capacity in proportion to decreased C3 and B levels • Decreased PMN chemotaxis; early depletion of marrow storage reserves • Decreases lymphocyte motility or adherence Extrinsic/iatrogenic/Factors: • Cutaneous barriers violated • Indwelling intravascular devices • Suppression of normal flora by antimicrobials • Tracheal intubation • Consequences of oxygen therapy • Multiple exposures to pathogensPremature, LBW Infants Surveillance for nosocomial infection: prompt recognition of outbreaks; initiation of control measures Appropriate handwashing procedures are the single most important aspect. Isolation procedures: based on mode of transmission seem to have an outbreak you could even decide to close your nursery to preadmissions while the outbreak is brought under control. Appropriate handwashing procedures are the single-most important aspect of preventing infections, not only in low birth rate preterm babies, but in immunocompromised patients. Gloves are not a substitute for handwashing. Isolation procedures. Among preemies who are less than 32 weeks gestation, almost one-half have BPD, and about onequaarte are without BPD. Preemies less than 32 weeks frequently require rehospitalization within a short period of time.in LBW Infants Among premature infants <32 wk gestation 45% with bronchopulmonary dysplasia (BPD), require re-hospitalizatiion and 25% without bronchopulmonary dysplasia (BPD), require re-hospitalization Premature infants without BPD require re-hospitalization at a rate 10-fold higher than term infants BPD infants are more likely to require multiple re-admissions and prolonged stays than those without lung disease Infants discharged before RSV and influenza season (July-Dec.) are significantly more likely to be readmitted than infants discharged in other months Increased airway resistance and bronchial hyperreactivity add to predisposition of BPD infants to viral (especially RSV) and bacterial pneumonias Presumptive therapy is indicated for infections in infants with BPD than 37 weeks gestation is getting neonatal sepsis, incideenc is 10-fold higher than the risk of a term baby getting neonatal sepsis, and If this risk persists, the immunologic problems persist and, therefore, the attack rate persists. If you have babies with BPD, they are much more likely to require hospital readmissions, and they are much more likely to require a full month stay than those without lung disease. From July to December preemies are more likely to be expoose to RSV during the RSV and other respiratory virus season, and if you are exposed, you are more likely to be readmitted. So the respiratory virus is responsible for this seasonal distribution of readmissions. Increased airway resistance and bronchial hyperactivity add to the predisposition of bronchopulmonary dysplasia infants to viral illnesses. Abnormal lung mechanics, abnormal immunnit makes you more susceptible both to viral and bacteriia infections. Presumptive therapy is indicated for infections in infants with BPD.Definition: Infection of the umbilicus Predisposing Features: LBW infant; complicated delivery Incidence: 2% Onset: Mean age 3 days Agents: S. aureus, group A streptococci, Bacteroides deliveries. The mean age of onset is three days, and the pathogens that we are thinking about are staph aureus, group A streptococcuus bacteroids. Group A strep is on the list if the newborn goes home because a sibling with impetigo, touches that moist cord before it dry. Group A strep is very easily transmisssibl and very rapidly progressive, and so the infant will present quite quickly.Inflammation of the Umbilical Cord Agents • Group A Streptococcus: wet, malodorous umbilical stump with minimal inflammation • Syphilis: "necrotizing funisitis," umbilical cord swollen, discolored red, white and blue--resembling a barber's pole. Involves matrix with perivascular inflammation and obliterative endarteritis • Candida: in association with congenital cutaneous disease chorioamnionitis, for example, without the isolation of an organism. Syphilis could be a diagnostic possibility if you have the placenta and the cord remaining. For the diagnosis of congennita syphilis, it can cause a necrotizing funisitis of the umbilical cord, and the cord is swollen, and it has a barber pole appearance (red, white, and blue). This involves matrix perivascular inflammation and then endarteritis, so you see this red, white, and blue thing. You see the red is the inflammattion the white and the blue are manifestations in the endoarteritis thrombosis, and lack blood flow to those particulla areas. Diagnosis and Therapy • Culture from purulent exudate or subcutaneous aspirate (differentiate from colonization) (omphalitis/funisitis) • Histopathologic evaluation of cord (funisitis) • Parenteral antibiotics and, for streptococcal funisitis, topical treatment (triple dye or antibiotic) funisitis, you cut the cord. Histologic examination will show the inflammation. Parenteral antibiotics are indicated in these particular situations most of the time. Colonizes urogenital tract of ~50% of healthy adults Accounts for 20-30% of non-chlamydial NGU cases Associated with spontaneous abortion, chorioamnionitis and fetal demise; causation? Vertical transmission rate during vaginal delivery is ~50% Colonizes the eyes, throat, umbilicus and perineum of newborns; may persist for months this organism requires urea for its metabolic pathway. It colonizes the urogenital tract in 50% of healthy adults, so it is a very common colonizer in sexually active adults. It accouunt for 20% to 30% of nonchlamidial NGU cases. It is associated with spontaneous abortion, chorioamnionitis and fetal demise; but the organism may not necessarily be causiin these events. Vertical transmission during vaginal delivery occurs about 50%, so if your pregnancy population is colonized 50%, you can know that about one in four babies might be colonized with this organism. The colonization sites in the newborn are the eyes, the throat, the umbilicus, and the perineum, and this persists for many months. It may last six to twelve months, then it goes away, and you do not see ureaplasma again until the age of sexual activity, and then you go up to 50%. Infants Associated causally with 'pneumonia' in some low birth weight infants, but incidence and impact is uncertain Presence in tracheal aspirate cultures does not predict respiratory deterioration in low birth weight, intubated infants with lung disease It has been isolated from CSF of preterm infants; pathologic role is unclear Isolation requires special transport media and urea-containiin broth Erythromycin (25-40 mg/kg/day in 4 doses) for 10 days is treatment of choice gestation infants, but the exact incidence is unknown, and the impact of these lung abnormalities are unknown. If you have somebody with radiographic lung disease and you grow ureaplasma urealyticum from tracheal aspirate secretions, erythromycin is the drug of choice here, just like with Chlamydia, the optimal duration is ten days. It has been isolated from the CSF of preterm infants with or without cell inflammation signs in its spinal fluid, but its pathological role is not clear at this time. Source usually is maternal but nosocomial acquisition is possible Predisposing factors include maternal chorioamnionitis, preterm delivery, and prolonged rupture of membranes 50% of cases have onset <7 days of age (3-7 most common) K1 capsular polysaccharide-containing strains: ~40% of bacteremias, 75% of meningitis cases infection. With E. coli, nosocomial transmission is possible. Usually we are talking about late onset acquisition when we are talking about nosocomial acquisition. The predisposing factors include the same kinds of maternal factors that predispose patients to infection with other agents besides E. coli, such as maternal chorioamnionitis. Preterm delivery and prolonged rupture of membrane. Half of those started in the first seven days of life. It was interesting that there was a peak between age three and age seven, and then a later peak of late onset disease. Initial Therapy: ampicillin and gentamicin or ampicillin and cefotaxime when gram-negative meningitis suspected Modify antimicrobial therapy based on susceptibility testing; minimum duration 21 days Assess ventricular status early (head ultrasound or CT) Case-fatality rates (15-40%); neurologic sequelae mandate careful audiologic and neurologic follow-up onset meningitis, and this is quite adequate initially, realizing that some strains are going to be ampicillin resistant. Ampicillin and cefotaxime, would be used, based on susceptibiility 21 days of therapy is required. Some complicated patients, especially those with ventricular illnesses are going to require longer term therapy for cure. Ventriculitis with obstruction must be determined early, and the easiest way to do that is with a head ultrasound. If you see ventricular dilatation then you can suspect there is a block and you may need to assess the ventricular fluid as part of your culture follow-up and efficacy of cure. If you have ventriculitis, if the CSF is sterilized, ventricular fluid is persistenntl positive, that is going to be a patient who is going to relapse if you treat only 21 days and you need to treat longer. The case fatality rates are still substantial. Case fatality is 15% to 20%. Perinatal Period • Transplacental or ascending intrauterine infection • Exposure during delivery • Environmental sources (late-onset disease) is something that can be transmitted transplacentally, or you can see ascending intrapartum transmission like the more typical neonatal pathogens. This may be going on for a very long time at the time you see the baby. Exposure during delivery may also occur with Listeria, and the clinical syndroome that you see with exposure during delivery are quite similar to the clinical syndrome with E. coli , sepsis and group B strep sepsis. The distinctive feature of Listeria is the ability to pass the placenta early on and cause quite a distiinc transplacental syndrome. Pregnant women are also vulnerable. Listeria colonization of the genital tract is uncommoon but when it is there it may be associated with preterm delivery and other obstetric complications. The most commmo one is chorioamnionitis. These women are quite ill. They do fine with appropriate antimicrobial therapy, but they have high fever, leukocytosis, and flu-like syndrome. Food-borne Listeria has a variety of sources related to food. Contaminated dairy products is the big one because Mexican goat cheese is a favorite. Maternal genital tract occurs in association with preterm delivery and other obstetric complications (e.g. amnionitis) Food-borne • Contaminated dairy products • Undercooked poultry • Prepared meats (pate, hot dogs) • Cabbage contaminated with animal manure outbreaks of listeriosis. Remember that the mother may eat these things and transmit the organism to the fetus. When the baby develops listeriosis, the mother may say that she has not been that ill but she has had some sort of a viral illness. In more than half of the babies, an intrapartum history of amnionitis is present.Associations Maternal • Fecal or genital carriage • Amnionitis • Flu-like illness (fever, malaise, headache, myalgia) Infant • Mother with symptomatic prodrome (65%) or amnionitis Decreased Cell-mediated Immunity • Cancer chemotherapy; steroid therapy; congenital immunodeficciency HIV disease; hepatic or renal disease Healthy Host • Ingestion of contaminated food mediated immunity are at risk for listerial infections. The one thing to remember is that healthy people with a contaminated food exposure may become ill with Listeria, and occasionally present with high fever, flu-like symptoms and documentation of bacteremia or occasionally meningitis. Infection (<16 wks) may cause abortion or stillbirth Maternal influenza-like illness occurs 2-14 days before delivery; delivery is often precipitated by recurrence of fever Chorioamnionitis is frequent, favoring the transplacental route of transmission Maternal recovery is usually complete illness. If you have somebody in July who has a flu-like illneess you should be suspicious. If it’s a pregnant woman, ery, and it may be precipitated by recurrence of fever at the time of delivery. Meconium staining (green or brown amniotic fluid), cyanosis, apnea, respiratory distress at delivery Common signs of infection: pneumonia (with hypoxia), sepsis, meningitis (less common) Granulomatous rash with 1-2 mm microabscesses (erythematous base) on skin and in pharynx analogy in terms of age of onset, birth weight, obstetric usually a bacteremic illness early, and a meningeal focus late. Case fatality ratios are going to be significantly higherOnset 1-8 weeks of age (male predominance) Major form of infection is meningitis Symptoms are not distinctive (fever, irritability, lethargy, poor feeding) CSF pleocytosis (150-3,000 WBC/mm3) early monocytic then later, lymphocytic predominance help with a diagnosis in addition to cultures. There seems to be a male predominance. The age of onset goes into the month. The major form of late onset infection is meningitis and the symptoms are not distinct. These patients present a diagnosis by doing a lumbar puncture. Clinical Settings • Renal transplantation, malignancy, HIV infection Usual Presentations • Meningitis or sepsis Less Common Manifestations • Rhomb encephalitis, brain abscess, arthritis, osteomyelitis, endocarditis, endophthalmitis, peritonitis Infection in Normal Host • Occurs, but rarely rhomboencephalitis, brain abscess, osteomyelitis, and endocranitis. Ampicillin, penicillin, erythromycin, tetracycline are bacteriostatic; TMP-SMX, ampicillin appear bactericidal Recommended initial regimen: ampicillin and gentamicin (combination is bactericidal); then ampicillin alone Penicillin-allergic patient: vancomycin and gentamicin or (for non-perinatal infections) TMP-SMX Cephalosporins are not active against Listeria nervous system infections, most people use combination therapy initially, and complete therapy with ampicillin. Ampicillin is usually preferred because it is more active and in vitro. Cephalosporins are not active. and Infant Colonization Vertical transmission in 50% of infants born to GBS colonized women (not given intrapartum penicillin) Neonatal colonization: >24 hrs = rectum > throat > umbilicus >30 days = rectum >throat Onset of sexual activity Sites = gastrointestinal tract > genital > throatGBS Infection Feature Early-Onset Late-Onset Mean age at onset 8 hr 27 days Incidence 13-3.7/1000 live births 0.6-1.7/1000 live births Obstetric complicaation Common Unusual Manifestations Pneumonia (40%) Bacteremia (45%) Meningitis (15%) Bacteremia (50%)Meningitis (35%) Serotypes All Type III predominaate Fatality rate 8-6% 2-10%GBS During Pregnancy Screening at 26-28 weeks gestation has PPV of 73% and NPV at 92% for colonization status at delivery; at 35-37 weeks, these increase to 96% and 100% Swab of lower vagina and anorectum necessary to define colonization Process culture in selective broth mediumDiagnosis Antibiotic Dose (per kg/d) Duration (days) Meningitis Ampicillin +gentamicin then penicillin G 300-400 mg 7.5 mg then 400,000-500,000 U Until CSF sterile and susceptibility known; compllet 14-21 Bacteremia , soft tissue infection pneumonia Penicillin G 150,000-200,000 U 10 Septic arthritti Penicillin G 200,000 U 14-21 Osteomyelitis Penicillin G 200,000 U 21-28 Endocarditis Penicillin G plus gentamicin for the initial 7-14 days 300,000-400,00 U >28Choice of obstetrical strategies: GBS culture-based or risk factor-based Penicillin G IV (5 MU initially; 2.5 MU Q4h) until delivery (alternatives = clindamycin or erythromycin) Timing: 4 hours (>2 doses) before delivery assures greatest efficacy (Pylipow, Pediatrics 1994;98:631-5)Baker CJ, Edwards MS. 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Role of Ureaplasma urealyticum and Chlamydia trachomatis in development of bronchopulmonary dysplasia in very low birth weight infants. Pediatr Infect Dis J 1997;16:364-369. Glaser JH. Ureaplasma urealyticum. In: Long SS, Pickering LK, Prober CG, editors. Principles and practice of pediatric infectious diseases. New York: Churchill Livingstone, Inc., 1997; 1111-1114. Klein JO, Remington JS. Current concepts of infections of the fetus and newborn. In: Remington JS, Klein JO, editors. Infectious diseases of the fetus and newborn infant. 4* ed. Philadelphia: W.B. Saunders Co., 1995; 1-19. Red Book of the American Academy of Pediatrics. Syphilis. 1997;504-514. Risks associated with human parvovirus B-19 infection. MMWR 1989;38:81-97.