PubMed Health⌕ Search

Biomedical subjects

R G Faix

Publications and source records attributed to R G Faix.

At least 19 recordsLinked to original sources

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.

Adult↗

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.

Amphotericin B↗

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 at steady state to 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) and group B (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.

Anti-Bacterial Agents↗

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.

Arteries↗

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.

Adult↗

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.

Chronic Disease↗

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.

Blotting, Southern↗

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.

Dobutamine↗

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.

Amphotericin B↗

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.

Adult↗

Spontaneous resolution of nonimmune hydrops fetalis secondary to human parvovirus B19 infection.

Many instances of nonimmune hydrops fetalis ascribed to human parvovirus B19 have been reported. The leading proposed pathophysiologic mechanism of hydrops in affected fetuses is viral invasion of red blood cell progenitors, causing a profound reticulocytopenic fetal anemia. Although the natural history of fetal parvovirus infection remains to be elucidated fully, there have been recent reports of funipuncuture and intrauterine blood transfusions to diagnose and manage this problem. We report two pregnancies in which parvovirus-related hydrops fetalis was observed to resolve without intervention, followed by uncomplicated vaginal deliveries of healthy infants. These observations emphasize the need for further investigation before recommending routine fetal blood transfusion in affected cases.

Adolescent↗

Invasive neonatal candidiasis: comparison of albicans and parapsilosis infection.

Severe infections caused by non-albicans Candida species are being increasingly reported among infants in neonatal intensive care units. To assess relative severity, mortality rates for C. albicans (CA) and C. parapsilosis (CP) infections in one neonatal intensive care unit from 1980 to 1990 were compared. Invasive candidiasis was defined as Candida recovery from a normally sterile body fluid or site with clinical signs of infection. Invasive candidiasis was diagnosed and systemic antifungal therapy initiated in 45 infants, 29 with CA and 16 with CP. No differences were found between CA and CP for birth weight, gestational age, age or weight at onset, presence of necrotizing enterocolitis, gastrointestinal or genitourinary anomalies, death (all causes), prior incidence or duration of antibiotics, parenteral nutrition, steroids or endotracheal intubation. Candida infection as the cause of death was more frequent with CA than CP (7 of 29 vs. 0 of 16; P = 0.034). Infants with CA were more likely to have antecedent thrush (P = 0.007) and perineal Candida dermatitis (P less than 0.02); those with CP were more likely to have vascular catheters at the time of positive culture (P less than 0.02). Though both pathogens occur in similar neonatal intensive care unit infants and can cause severe disease, CA appears more likely to result in death than CP.

Candida↗