Aminoglycoside-related nephrotoxicity in the premature newborn.

The nephrotoxicity of gentamicin and amikacin was compared during presumed sepsis in 107 premature neonates. To examine the possibility that nephrotoxicity was directly associated with the clinical conditions of "sepsis," a control group of 26 chloramphenicol-treated newborns was also studied. Two markers of proximal renal tubular injury, N-acetyl-beta-glucosaminidase (NAG) and beta 2-microglobulin, were measured in 6-hr aliquots of urine. Because urine creatinine excretion increased with postconception age, markers were expressed in terms of excretion rate rather than per milligram of creatinine. The NAG excretion rate was significantly higher in gentamicin-treated patients (138 +/- 10 U/min, mean +/- SE) than in amikacin-treated patients (85 +/- 7 U/min) but did not differ between patients treated with amikacin and those treated with chloramphenicol (81 +/- 11 U/min). Excretion of beta 2-microglobulin did not differ among the three patient groups. We conclude that amikacin may be less nephrotoxic than gentamicin in the premature newborn.

Sequelae of acute bacterial meningitis in children treated for seven days.

The sequelae of acute bacterial meningitis in children who were treated with ampicillin or chloramphenicol for seven days during the period January 1979 to June 1983 were assessed prospectively. The 235 patients (117 boys and 118 girls) ranged in age from four days to 18 years (mean 26.4 months). Haemophilus influenzae type b was isolated in 70% of patients, Streptococcus pneumoniae in 20%, and Neisseria meningitidis in 10%. The mortality rate was 6.4%. No relapses occurred. Of the 220 survivors, 171 had neurologic psychometric, audiologic, and ophthalmologic assessments performed for a minimum of 1 year following their illness. One hundred thirty-six (80%) children had no detectable sequelae; 20% had mild to severe handicaps. The frequency of sequelae was greatest among children with S pneumoniae meningitis (57%) and least among children with N meningitidis (0%). The sequelae observed included: sensorineural hearing loss (12.9%), developmental delay (5.3%), speech defect (4.7%), motor defect (3.0%), hydrocephalus (1.7%), and seizure disorder (1%). The frequency of observed sequelae among these patients is similar to that previously reported in children treated for ten to 14 days. Our findings indicate that seven days of intravenous antibiotic therapy is adequate for the treatment of bacterial meningitis in children.

Haemophilus influenzae type b in a nursery school: the value of biotyping.

Meningitis due to Haemophilus influenzae serotype b biotype II occurred in a 2-year-old child who attended a nursery school along with 26 other 2-year-old children. Nasal swabs from these 26 contacts revealed a H influenzae type b colonization rate of 50% (13/26); simultaneously performed throat swabs detected a colonization rate of 4% (1/26). Biotyping of the H influenzae type b isolates revealed that only 46% (6/13) were the same biotype as the index case; the remaining seven isolates were biotype III. All children received treatment with 20 mg/kg/day of rifampin administered by the nursery school attendant as a single dose for four days before the results of the cultures were known. Eradication of H influenzae type b carriage was successful in three of the six biotype II carriers and five of the six biotype III carriers available for follow-up culture. It was concluded that: (1) the culture site utilized in determining H influenzae type b colonization rates may markedly influence the results obtained; (2) biotyping may be a valuable epidemiologic tool in investigating the contacts of patients with H influenzae type b disease, and (3) failures of rifampin to eradicate the carriage of H influenzae type b from the nasopharynx may occur. The prudent approach to the management of young contacts of patients with serious H influenzae type b disease is to recognize their high risk status and to maintain close surveillance of them. The role of chemoprophylaxis with rifampin remains to be established.

Pharmacokinetic optimisation of the treatment of septic arthritis.

Early diagnosis and treatment of septic arthritis improves the potential for a favourable outcome. Optimal treatment includes the prompt and judicious use of effective antimicrobial agents coupled with prompt drainage of the affected joint. Adequate drainage may be accomplished by means of repeated closed large-bore needle aspiration, arthroscopy, or an open surgical procedure. The purpose of this article is to describe optimal antimicrobial therapy based upon available pharmacokinetic data. The host-dependent vulnerability to specific pathogens, local antibacterial susceptibility patterns and knowledge of antibacterial activity at the site of infection must all be taken into account when planning appropriate treatment. This article does not address arthritis secondary to human and animal bites, diabetic foot infections, mycobacteria, fungi, Lyme spirochaete, or other nonbacterial causes of septic arthritis.

Vancomycin pharmacokinetics in very low birth weight neonates.

The pharmacokinetics of vancomycin hydrochloride was studied in 12 very low birth weight infants. The gestational age (mean +/- SD) was 25.9 +/- 1.3 weeks and body weight was 769.2 +/- 151.5 g at the time of initiation of the study. Vancomycin was infused over a period of 60 minutes in a dosage of 14.2 +/- 3.2 mg/kg once daily in 10 patients, twice daily in 1 patient and every 36 hours in 1 patient for a mean of 10.5 +/- 4.9 days. Serial blood samples were obtained and the concentration time data were fitted to a one-compartment open model using the ADAPT computer program. A significant positive correlation was found between postconceptional age and vancomycin clearance (P less than 0.005) and between vancomycin elimination half-life and plasma creatinine (P less than 0.01). A negative correlation existed between plasma creatinine and vancomycin clearance (P less than 0.005), between postconceptional age and plasma creatinine (P less than 0.005) and between vancomycin half-life and postconceptional age (P less than 0.01). On the basis of these findings a vancomycin dosage of 15 mg/kg every 24 hours for infants less than 1000 g should yield concentrations within the accepted therapeutic range. This susceptible population requires frequent monitoring of vancomycin concentrations because of the high degree of interpatient variability and the continuous maturation of renal function.

Gentamicin pharmacokinetics in neonates undergoing extracorporal membrane oxygenation.

We evaluated the effects of extracorporeal membrane oxygenation (ECMO) on the pharmacokinetics of gentamicin in 18 infants who underwent ECMO therapy for severe respiratory failure and received gentamicin for possible sepsis. Twelve of these infants continued to receive gentamicin after ECMO had been discontinued. The volume of distribution (Vd) of gentamicin in the newborns receiving ECMO was 0.58 +/- 0.04 liter/kg, compared with a Vd of 0.45 +/- 0.02 liter/kg after ECMO had been discontinued (P = 0.02). The clearance of gentamicin in the patients undergoing ECMO was 42 +/- 3 ml/kg/hour compared with 57 +/- 4 ml/kg/hour in those patients off ECMO (P = 0.003). The elimination half-life in patients receiving ECMO was 10.0 +/- 0.7 hours compared with 5.7 +/- 0.4 hours after ECMO had been discontinued (P less than 0.0001). Neonates undergoing ECMO demonstrate a higher volume of distribution of gentamicin, a lower clearance, and consequently a longer half life for this drug. We conclude that gentamicin and probably other aminoglycosides should be given at dose rates about 25% lower than usual and at longer dosing intervals in patients undergoing ECMO therapy.

False positivity of Legionella serology in patients with cystic fibrosis.

Respiratory deterioration accounts for the morbidity and mortality observed in patients with cystic fibrosis. The role of Legionella in this deterioration was determined in a 2-year prospective study of 49 patients with cystic fibrosis and 19 sibling controls. Sera were obtained from participants on enrollment and at quarterly intervals. Legionella antibodies were measured in parallel using an indirect fluorescent assay. No seroconversions were observed. Eleven of 49 patients with cystic fibrosis (22%) were seropositive compared to none of 19 siblings (P less than 0.05). Six of the 11 patients demonstrated high titers (greater than or equal to 1:512) that persisted throughout the study. Absorption with pools of various Pseudomonas species reduced the antibody titers such that only 3 remained positive after absorption. Legionella was not found to be an important cause of clinical deterioration during this study. The results of the absorption studies suggest that high titers to Legionella in this population are due to cross-reacting antibodies.

A prospective evaluation of primary genital herpes simplex virus type 2 infections acquired during pregnancy.

In order to study the epidemiology of herpes simplex type 2 (HSV-2) infections during pregnancy, we used an enzyme immunoassay to detect type-specific antibodies to HSV-2 glycoprotein G in serial blood samples obtained from a cohort of 1891 pregnant women. Blood samples obtained at about 17 and 32 weeks of gestation and at the time of delivery were assessed for antibody to HSV-2 glycoprotein G in order to evaluate the prevalence of past infections with HSV-2 and the rate of acquisition of HSV-2 infection during pregnancy. Three hundred eleven pregnant women (16.5%) were found to have had past infections with HSV-2. Four of the 1580 women who were initially seronegative developed antibodies to HSV-2 during pregnancy. The annualized rate of acquisition of HSV-2 infection in pregnant women was 0.58%. Three of four women had asymptomatic primary infections; all of the women had preexisting HSV-1 immunity. None of the women or their infants experienced any adverse consequences of gestational herpes. Based upon our very limited number of observations to date, asymptomatic primary episodes occurring in women with previous HSV-1 immunity may be of less consequence to the fetus and neonate than symptomatic true primary HSV-2 infections.

Storage and transport of cultures for Herpes simplex virus, type 2.

Tryptic soy broth and brain-heart infusion broth maintained herpes simplex virus within +/- 1 serial dilution of the original titer in all of 51 samples held for one to three days at 4 C. In contrast, holding temperatures of -20 C or 22 C resulted in losses of titer of 10(2) or more. Holding periods as long as five days prior to inoculation did not delay the appearance of the cytopathic effect following inoculation. Unmodified tryptic soy broth or brain-heart infusion broth and holding periods as long as three days at 4 C prior to arrival in the laboratory give as satisfactory results as do traditional viral culture media and prompt inoculation of the specimen.

Pediatric resident training in a school environment. A prescription for learning.

OBJECTIVE: To describe our experience with developing, implementing, and evaluating the educational effect of a school health experience for pediatric residents. DESIGN: Descriptive. SETTING: University-based pediatric residency program and five public elementary and middle schools in surrounding communities. PARTICIPANTS: Eleven pediatric residents. INTERVENTION: A school health experience for pediatric residents was developed in response to the report of the American Academy of Pediatrics Task Force on Pediatric Education and the new training recommendations of the Residency Review Committee of the American Council for Graduate Medical Education. Residents spent 3 weeks in the schools engaged in teaching and observational activities. MAIN OUTCOME MEASURES: Questionnaires of residents' attitudes and knowledge, structured resident interviews, and teacher questionnaires. RESULTS: Positive effect on resident's knowledge of school structure, child development, communication with children, school-related problems, and special education. Positive effects on resident's attitudes about teamwork between teachers and pediatricians and roles of pediatricians in schools. Teacher feedback showed acceptance by the school community. CONCLUSIONS: Pediatric residents benefit from exposure to children in school settings. Schools provide an opportunity to observe normal childhood development and behavior in a more natural setting than that provided in the hospital.

Genital herpes during pregnancy: inability to distinguish primary and recurrent infections clinically.

OBJECTIVE: To determine if the signs and symptoms of genital herpes in pregnancy accurately identify primary genital herpes infections using serologic testing for final classification. METHODS: Twenty-three women with clinical signs and symptoms suggestive of primary genital herpes infections in the second and third trimesters of pregnancy were subsequently cultured and tested serologically (for herpes simplex virus type 1 and herpes simplex virus type 2 antibodies) and classified as having true primary (no herpes simplex virus type 1 or type 2 antibodies), nonprimary (heterologous herpes simplex virus antibodies present), or recurrent (homologous antibodies present) infections. RESULTS: Only one of 23 women with clinical illnesses consistent with primary genital herpes virus simplex infections had serologically-verified primary infection. This primary infection was caused by herpes simplex virus type 1. Three women had nonprimary type 2 infections, and 19 women had recurrent infections. Among culture-proven recurrent infections, 12 were caused by herpes simplex virus type 2 and three by herpes simplex virus type 1. Only one infant was born preterm, and no clinically significant perinatal morbidity was observed. CONCLUSION: Correct classification of gestational genital herpes infections can be accomplished only when clinical evaluation is correlated with viral isolation and serologic testing using a type-specific assay. Severe first episodes of genital herpes infections among women in the second and third trimesters of pregnancy are not usually primary infections and are not commonly associated with perinatal morbidity.

Epidemiology of herpes simplex virus type 2 infections in a high-risk adolescent population.

The seroprevalence of infection with type 2 herpes simplex virus (HSV-2) was determined in 135 adolescents detained in a juvenile detention facility. A total of 16% of enrollees were seropositive for HSV-2. Age of onset of sexual intercourse, number of lifetime partners, frequency of condom use, and history of sexually transmitted diseases did not predict HSV-2 seropositivity.

The white cell ratio in the very low birth weight infant.

The purpose of this study was to assess the usefulness of the white cell ratio of immature neutrophils (PMNs) to total (immature plus mature) PMNs as an indication of infection in the very small premature infant. We retrospectively reviewed the charts of 59 premature infants less than or equal to 1,250 g admitted to our Newborn Intensive Care Unit over a one-year period who had at least one white count determined. Twenty-three were born after rupture of membranes for greater than or equal to 24 hours (PROM), 47 had a one-minute Apgar score less than or equal to 6 and 31 had a five-minute Apgar scores less than or equal to 6, 38 had respiratory distress syndrome (RDS), and 4 had confirmed infection. Thirty-one of the infants had a ratio greater than or equal to .15 in the first day of life, a value which has been suggested in the literature as being abnormal and an indication to suspect sepsis. This ratio bore no statistical relationship to PROM, low Apgar scores, or RDS. We analyzed these same relationships using a ratio greater than or equal to .25, another ratio derived from data in the literature which has been said to suggest infection. No statistical correlation was found for low Apgars or RDS, but there was a significant relationship between PROM and attainment of a ratio greater than or equal to .25 (p less than .005). It is notable that 2 out of the 4 infants with infection had a ratio less than .15. We wish to cast doubt on the applicability of the currently defined WBC ratios in the literature as they apply to the infant with birth weight less than 1,250 g and emphasize the apparent effect of PROM as a factor upon these ratios.

Encephalitis. Identifying the specific cause is key to effective management.

Acute viral encephalitis and postinfectious encephalomyelitis affect both children and adults. Enteroviruses, HSV types 1 and 2, and arboviruses are the most common causes of encephalitis in the United States; however, the differential diagnosis is broad. History taking and physical examination can provide clues to the cause, but the diagnosis is usually established on the basis of CSF analysis, viral culture, MRI, and serologic testing, when indicated. In the future, PCR techniques may enhance rapidity of diagnosis. Until the specific cause is identified, empirical therapy should be given. Because complications can be severe, all patients with encephalitis should be monitored in a facility capable of providing supportive intensive care. Long-term follow-up is important to detect sequelae, particularly in patients with eastern equine or HSV encephalitis.