Evolving blood pressure dynamics for extremely preterm infants.

OBJECTIVE: To examine changes in arterial blood pressure (ABP) after birth in extremely preterm infants. STUDY DESIGN: Prospective observational study of infants 23(0/7) to 26(6/7) weeks gestational age (GA). Antihypotensive therapy use and ABP measurements were recorded for the first 24 h. RESULT: A cohort of 367 infants had 18 709 ABP measurements recorded. ABP decreased for the first 3 h, reached a nadir at 4 to 5 h and then increased at an average rate of 0.2 mm Hg h(-1). The rise in ABP from hour 4 to 24 was similar for untreated infants (n=164) and infants given any antihypotensive therapy (n=203), a fluid bolus (n=135) or dopamine (n=92). GA-specific trends were similar. ABP tended to be lower as GA decreased, but varied widely at each GA. CONCLUSION: ABP increased spontaneously over the first 24 postnatal hours for extremely preterm infants. The rate of rise in ABP did not change with antihypotensive therapy.

Evaluating retinopathy of prematurity screening guidelines for 24- to 27-week gestational age infants.

OBJECTIVE: To determine whether current retinopathy of prematurity (ROP) screening guidelines adequately identify treatable ROP in a contemporary cohort of extremely low gestation infants. STUDY DESIGN: Data from the Surfactant, Positive Pressure, and Pulse Oximetry Randomized Trial were used. Inborn infants of 24 (0)/7 to 27 (6)/7 weeks gestational age (GA) with consent before delivery were enrolled in 2005 to 2009. Severe ROP (type 1 ROP or treatment with laser, cryotherapy or bevacizumab) or death was the primary outcome for the randomized trial. Examinations followed the then current AAP (American Academy of Pediatrics) screening recommendations, beginning by 31 to 33 weeks postmenstrual age (PMA). RESULT: One thousand three hundred and sixteen infants were enrolled in the trial. Nine hundred and ninety-seven of the 1121 who survived to first eye exam had final ROP outcome determined. One hundred and thirty-seven (14% of 997) met criteria for severe ROP and 128 (93%) of those had sufficient data (without missing or delayed exams) to determine age of onset of severe ROP. PMA at onset was 32.1 to 53.1 weeks. In this referral center cohort, 1.4% (14/997) developed severe ROP after discharge. CONCLUSION: Our contemporary data support the 2013 AAP screening guidelines for ROP for infants of 24 (0)/7 to 27 (6)/7 weeks GA. Some infants do not meet treatment criteria until after discharge home. Post-discharge follow-up of infants who are still at risk for severe ROP is crucial for timely detection and treatment.

Maternal and transplacental pharmacokinetics of cefazolin.

OBJECTIVE: To evaluate the intrapartum pharmacokinetics of cefazolin, including delivery to amniotic fluid (AF) and fetal compartments, and to ascertain that adequate cefazolin concentrations are attained to exceed the mean concentration inhibiting 90% (MIC(90)) of group B streptococcus strains. METHODS: Cefazolin (1 g) was administered intravenously at five separate time intervals (0.5, 1, 2, 4, and 6 hours) before elective cesarean at term to 26 women with intact membranes and with no significant infections or cardiovascular, liver, or renal disease. Samples of maternal blood, cord blood, and AF were obtained at the time of delivery. Exact collection times relative to cefazolin infusion were noted. Amniotic fluid contaminated with blood or meconium was excluded. Cefazolin concentration was measured by high-pressure liquid chromatography. RESULTS: All maternal and cord plasma cefazolin levels, except one, were above the MIC(90) for Streptococcus agalactiae (group B streptococcus). For AF, all cefazolin levels, except two, were above the MIC(90). CONCLUSIONS: Cefazolin concentrations greater than or equal to the MIC(90) for group B streptococcus were attained in nearly all maternal, fetal, and AF samples. This information, together with the knowledge that there is rare resistance of group B streptococcus to cefazolin, supports the use of cefazolin as a better alternative than clindamycin or erythromycin for group B streptococcus prophylaxis in patients with a nonanaphylactic penicillin allergy.

Persistently positive cultures and outcome in invasive neonatal candidiasis.

BACKGROUND: A persistently positive culture >24 h after starting antibiotic therapy has been correlated with adverse outcome in several invasive bacterial infections, but few reports address persistent positivity and outcome in infections caused by fungi and other pathogens that replicate more slowly and therefore may succumb less quickly to therapy. METHODS: To assess whether positive culture >24 h after achieving target doses (amphotericin > or =0.5 mg/kg/day or fluconazole > or =6 mg/kg/day) of systemic antifungal therapy predicts focal infectious complication(s) or death from infection, we compared neonatal intensive care unit infants who had persistent (P+) or nonpersistent (P-) positive cultures with invasive candidiasis (clinical signs of infection and recovery of Candida from a normally sterile site) at this center from January 1, 1981, through June 30, 1999. Infants who died < or = 24 h after attaining target dosing, recovered without therapy, had a focal infectious complication already present at the time target dosing was achieved or were diagnosed with invasive candidiasis only postmortem were excluded. RESULTS: We identified 58 P+ (29, 12 and 7 had positive cultures for >7, >14 and > or =21 days, respectively) and 38 P- infants. No differences were found between P+ and P- for birth weight; gestational age; gender; onset age; central vascular catheters; necrotizing enterocolitis, surgery or bacterial sepsis; or duration of parenteral nutrition, antibiotics, tracheal intubation or postnatal steroids. P+ were more likely to have blood or cerebrospinal fluid involvement (68 vs. 45%, P = 0.03). Distribution of Candida species was similar (albicans in 53 vs. 63% for P+ vs. P-). P+ were significantly more likely to develop later "fungus ball" uropathy (16 of 56 vs. 2 of 32, P = 0.01), to develop renal infiltration (11 of 56 vs. 1 of 32, P = 0.03) and to die from invasive candidiasis (11 of 58 vs. 0 of 38, P = 0.003) than P-. P+ were also more likely to develop endocarditis, abscess, ventriculitis and invasive dermatitis, although P > 0.05. Focal complication increased as duration of P+ increased (48, 55, 67 and 71% at >1, >7, >14 and > or =21 days, P = 0.06). When comparing only those with positive blood and/or cerebrospinal fluid culture, similar patterns were observed, although only death and focal complication or death from invasive candidiasis attained significance. CONCLUSIONS: These observations suggest that in neonatal invasive candidiasis: (1) cultures usually remain positive >24 h after attaining target antifungal doses; (2) aggressive imaging for focal complications may be reserved for infants with persistently positive cultures after several days of antifungal therapy at target doses or have signs strongly suggestive of focal complication; (3) focal complications and/or death from candidiasis increase with persistence; (4) focal complications increase with duration of persistence; (5) serial culture of infected site(s) helps predict outcome and the need for aggressive surveillance and intervention for focal complications.

Lack of vancomycin-associated nephrotoxicity in newborn infants: a case-control study.

OBJECTIVE: The purpose of this study was to compare the incidence of nephrotoxicity, defined as doubling of baseline serum creatinine concentration, in newborn infants with peak vancomycin serum concentrations 40 microg/mL. A secondary objective was to correlate concomitant disease states and potentially nephrotoxic drug therapy with rises in serum creatinine in vancomycin recipients. METHODS: Newborn infants with culture-proven Staphylococcus aureus or coagulase-negative staphylococcal septicemia who received vancomycin therapy for >3 days between 1985 and 1995 were identified from an existing database and a review of medical record. All 69 patients included in the study had serial serum creatinine determinations, including a baseline value within 48 hours of starting treatment with vancomycin, and serum vancomycin concentrations determined after at least three doses, with peak and trough concentrations determined 1 hour after a 60-minute infusion and 15 to 30 minutes before a dose, respectively. Infants with congenital renal or cardiac anomalies were excluded. Demographic characteristics, vancomycin dosing regimen, serum vancomycin concentrations and sample times, concomitant drug therapy, and disease states were recorded. Patients were divided into group A (peak vancomycin concentration 40 microg/mL). The change in serum creatinine concentration between the start and end of vancomycin therapy was determined. Nephrotoxicity was identified if serum creatinine doubled at any time from the start to the end of vancomycin therapy. Alternative definitions of nephrotoxicity (any rise in serum creatinine to >0.6 mg/dL or new abnormalities of urine sediment) were used in additional analyses. RESULTS: A total of 69 evaluable patients (gestational age, 28.9 +/- 3.0 weeks; birth weight, 1219 +/- 516 g) were identified, 61 in group A and 8 in group B. Six patients in group A underwent doubling of serum creatinine concentration during vancomycin therapy, whereas none in group B did so. Serum creatinine doubled to >0.6 mg/dL in only 3 infants (all in group A). Any increase in serum creatinine to >0.6 mg/dL was seen in 10 infants, 9 of whom were in group A. No confounding variable, including previous or concomitant underlying disease states associated with renal dysfunction or treatment with other potentially nephrotoxic agents, were associated with a significant rise in serum creatinine. CONCLUSION: Vancomycin-associated nephrotoxicity is rare in neonates, even with serum peak concentrations >40 microg/mL.

Ureaplasma urealyticum and chronic lung disease in very low birth weight infants during the exogenous surfactant era.

BACKGROUND: An association between recovery of Ureaplasma urealyticum from the respiratory tract of very low birth weight (VLBW) infants (< or =1500 g) and later chronic lung disease (CLD) was reported by several authors before the routine use of exogenous surfactant (SURF). We sought to assess whether this relation persists in the era of routine SURF. METHODS: We prospectively studied a cohort of 105 VLBW infants who required mechanical ventilation at < 12 h of age. Tracheal aspirates for U. urealyticum culture were obtained before administration of SURF or antibiotics. Clinicians were unaware of U. urealyticum status. Chest radiographs at 28 days were reviewed by a single pediatric radiologist, blinded to U. urealyticum status. Sample size was predetermined to detect a 30% increase in CLD among those with U. urealyticum recovery from tracheal culture (U. urealyticum-positive) with alpha <0.05 and beta <0.20. RESULTS: Of the study infants 22 were U. urealyticum-positive and 83 were U. urealyticum-negative. No differences were found between the groups for birth weight, gestational age, gender, inborn, antenatal or postnatal steroid use, SURF therapy, non-U. urealyticum infection, necrotizing enterocolitis, patent ductus arteriosus, intraventricular hemorrhage or cystic periventricular leukomalacia. At 28 days U. urealyticum-positive patients were significantly more likely to have CLD than U. urealyticum-negative [15 of 22 (68%) vs. 30 of 83 (36%); P < 0.02]. The U. urealyticum-positive patients also required significantly longer courses of supplemental oxygen and mechanical ventilation. No significant differences were found for CLD at 36 weeks postconception or duration of hospitalization, although type II error could not be excluded for these secondary endpoints. CONCLUSIONS: Respiratory U. urealyticum at or shortly after birth remains associated with CLD at 28 days despite routine use of SURF. Controlled trials of anti-Ureaplasma therapy in U. urealyticum-positive VLBWs as soon after birth as possible may determine whether CLD, duration of respiratory support and attendant costs can be decreased.

Frequent resistance of clinical group B streptococci isolates to clindamycin and erythromycin.

OBJECTIVE: To determine both the frequency of reported penicillin allergy in parturients and the frequency of resistance in vitro of clinical isolates of group B streptococci to clindamycin and erythromycin. METHODS: One hundred clinical isolates of group B streptococci were tested to determine the frequency of resistance to clindamycin, erythromycin, penicillin G, vancomycin, and cefazolin. The frequency of beta-lactam allergy and reported allergic reaction also were recorded for all consecutive laboring women during the 4-month study. RESULTS: The frequency of group B streptococcal resistance to clindamycin was 15% and to erythromycin was 16%. No isolates were resistant to penicillin G, vancomycin, or cefazolin. Twelve percent of the 963 women who delivered during the study reported a penicillin allergy, but only 30% of those could describe their allergic reaction. CONCLUSION: In vitro resistance of group B streptococci to clindamycin and erythromycin occurred frequently in this population. Whereas the importance of this finding in vivo is uncertain, it raises concern about the possibility of inadequate prophylaxis using currently recommended alternatives in penicillin-allergic patients. Artful questioning of women reporting penicillin allergy may lessen the likelihood of using these less desirable agents in the setting of intrapartum antimicrobial prophylaxis.

Successful treatment of neonatal arterial thromboses with recombinant tissue plasminogen activator.

Seven newborns were treated with recombinant tissue plasminogen activator for arterial thromboses. Complete lysis occurred in four of seven and partial in two of seven patients. Serious bleeding complications were observed in two of seven patients. This and published experience suggest that successful lysis with recombinant tissue plasminogen activator occurs in most patients and that hemorrhagic complications are unusual but are not.

Improving the timing of antibiotic administration to high-risk newborns.

OBJECTIVES: To describe the timing of initiation of administration of parenteral antibiotics to infants with suspected sepsis at birth, identify barriers to prompt administration, and assess the effectiveness of subsequent interventions designed to minimize these barriers. The goals were to administer antibiotics within 1 hour of the physician order and within 2 hours of birth with more than 80% compliance for both goals. STUDY DESIGN: Retrospective chart review and prospective interventions involved 488 infants born at the University of Michigan Medical Center with indications for antibiotic therapy at birth. After an initial audit of the charts of 56 infants and the identification of poor compliance with the goals, unit policies and educational programs were developed to facilitate timely antibiotic administration. After a second audit demonstrated improvement but failure to attain the target compliance rates, review of individual cases with the responsible physician and nurse was initiated. Time intervals between birth, writing the order for antibiotics, noting the order by the nurse, and administration of antibiotics were tracked for an additional 20 months after these interventions. RESULTS: Before the interventions, antibiotics were administered to 28% of infants within 1 hour of the physician order (mean +/- SEM 1.58 +/- 0.11 hours) and to 19% within 2 hours of birth (3.12 +/- 0.16 hr). By the conclusion of the study, antibiotics were administered to 87% (p < 0.0001) of infants within 1 hour of the physician order (0.79 +/- 0.04 hour; p < 0.001) and to 92% (p < 0.0001) within 2 hours of birth (1.26 +/- 0.06 hours; p < 0.001). CONCLUSIONS: Administration of the first dose of parenteral antibiotics to newborns with suspected sepsis at birth frequently takes more than 1 hour after the order is written and more than 2 hours after birth. Efforts to identify and minimize common barriers significantly improved the timing of antibiotic administration. Additional improvement was attained by means of continued surveillance and individual feedback to caregivers of infants when timing objectives were not fulfilled.

Group C streptococcal infection in a term newborn infant.

Group C streptococci were recovered from the cerebrospinal fluid of a term infant with symptoms whose mother had received intrapartum antibiotic therapy for chorioamnionitis. This case highlights that beta-hemolytic streptococci of Lancefield groups other than A or B can be isolated from a normally sterile site and should be considered as pathogens. It also underscores the potential importance of sampling cerebrospinal fluid in an infant with symptomatic suspected sepsis, especially in the setting of exposure to maternal antimicrobial agents.

Genotypic analysis of a cluster of systemic Candida albicans infections in a neonatal intensive care unit.

Five very low birth weight infants developed systemic Candida albicans infection during a 6-week period in an urban neonatal intensive care unit. In an effort to assess whether a common source outbreak was present, the genomic DNA of the clinical isolates was compared by EcoRI and XbaI restriction fragment analysis and Southern blot hybridization with 27A, a species-specific, transposon-like probe. Although the restriction fragment analysis suggested strong similarities among the isolates, the hybridization patterns demonstrated that all strains were genotypically distinct. The parallel use of at least two restriction enzymes was important for differentiating the isolates. Rapid genotypic analysis of clinical isolates from a cluster of C. albicans infections permits determination of whether a common source is probable, facilitates epidemiologic decisions and may reduce infection control measures and attendant costs.

Streptococcus mitis infection in newborns.

Although neonatal infections caused by Streptococcus viridans have been suggested to be less severe than those caused by classic neonatal pathogens, little is known about neonatal infections caused by specific species within this group of bacteria. We report six infants who had S. mitis isolated from blood culture. All were infected at < or = 3 days of age; five of the mothers had perinatal risk factors for neonatal sepsis. Five infants were preterm and three had birth weights < or = 2500 gm. Hematologic abnormalities were common. Two died as a result of the infection. Antibiotic susceptibility testing of four isolates revealed resistance to penicillin and ampicillin in three and resistance to gentamicin in two. In vivo resistance was not observed. S. mitis is not part of normal skin flora, should not be assumed to be a contaminant, and can cause severe neonatal disease. If S. mitis or S. viridans are recovered from a normally sterile body site and the patient fails to improve with penicillin therapy, it seems prudent to switch to vancomycin until susceptibility results are available.

Randomized, blind trial of dopamine versus dobutamine for treatment of hypotension in preterm infants with respiratory distress syndrome.

To compare the efficacy of dopamine and dobutamine for the treatment of hypotension (mean arterial blood pressure, < or = 30 mm Hg) in preterm (< or = 34 weeks of gestation) infants with respiratory distress syndrome in the first 24 hours of life, we enrolled 63 hypotensive preterm infants in a randomized, blind trial. Inclusion criteria required an arterial catheter for measurement of mean arterial blood pressure, treatment with exogenous surfactant, and persistent hypotension after volume expansion with 20 ml/kg (packed erythrocytes if hematocrit < 0.40, 5% albumin if > or = 0.40). Intravenous study drug infusions were initiated at 5 micrograms/kg per minute and then increased in increments of 5 micrograms/kg per minute at 20-minute intervals until a mean arterial blood pressure > 30 mm Hg was attained and sustained for > or = 30 minutes (success) or a maximum rate of 20 micrograms/kg per minute was reached without resolution of hypotension (failure). The study groups at entry were comparable for birth weight, gestational age, postnatal age, gender, birth depression, hematocrit < 0.40, heart rate, oxygenation index, delivery route, maternal chorioamnionitis, and maternal magnesium or ritodrine therapy. No infants in the dopamine group had a treatment failure (0/31; 0%); (16%) of 32 infants failed to respond to dobutamine (p = 0.028). Success was attained at < or = 10 micrograms/kg per minute in 30 (97%) of 31 infants given dopamine and in 22 (69%) of 32 infants given dobutamine (p < 0.01). Among those treated successfully, the increase in mean arterial blood pressure was significantly higher in those given dopamine (mean, 11.3 vs 6.8 mm Hg; p = 0.003). We conclude that dopamine is more effective than dobutamine for the early treatment of hypotension in preterm infants with respiratory distress syndrome.

Primary cutaneous aspergillosis in a preterm infant.

A case of primary cutaneous aspergillosis in a very low birthweight infant that responded to medical therapy is reported. Knowledge of the potential pathogenic role of this organism in neonatal skin lesions is important because of resistance to standard empirical antibacterial therapy and the potential for dissemination and deep parenchymal invasion. Surgical excision may be necessary if cutaneous aspergillosis progresses despite systemic antifungal therapy.

Increased nosocomial infection in neutropenic low birth weight (2000 grams or less) infants of hypertensive mothers.

The neutropenia often seen in infants of hypertensive mothers (IHMs) at < 12 hours of age has been associated with nosocomial infection in the first 18 days of life. To assess maternal hypertension as an independent factor for nosocomial infection, we compared 101 low birth weight (< or = 2.00 kg) IHMs to a concurrent birth weight-matched group of infants of normotensive mothers (INMs). Infants without differential leukocyte counts at < 12 hours of age were excluded, leaving 93 IHMs and 98 INMs. The incidence of neutropenia at < 12 hours among IHMs was not significantly different from that among INMs (42/92 (45%) vs 37/98 (38%)). Nosocomial infection was more frequent in neutropenic IHMs than in neutropenic INMs (12/42 vs 2/37; p = 0.007). Infection in IHMs included omphalitis (2 infants), pneumonia (4), and sepsis with or without meningitis (6); INMs had cellulitis (1) and sepsis (1). The underlying mechanism(s) for this predisposition remains to be elucidated, although limited data suggest that neutropenia may be more severe and prolonged among IHMs.