Diane E. Durrell

Malassezia furfur skin colonization of infants hospitalized in intensive care units

We studied the prevalence of Malassezia furfur skin colonization of infants hospitalized in our neonatal and infant cardiac and surgical intensive care units by culturing at monthly intervals. Of 361 infants studied over 1 year, 133 (36.8%) had at least one positive culture for M. furfur. Colonized infants, compared with noncolonized infants, had younger mean gestational age (32.4 vs 35.2 weeks, P less than 0.01), lower mean birth weight (1.76 vs 2.31 kg, P less than 0.01), a longer stay in hospital (Wilcoxon P less than 0.01), and more mean days use of an incubator (12.7 vs 7.6 days, P less than 0.01), lamb wool (12.9 vs 8.2 days, P less than 0.01), paper tape (10.8 vs 8.2 days, P less than 0.01), and Op-Site tape (14.1 vs 10.1 days, P less than 0.01). These data suggest that hospitalization in an infant intensive care unit often leads to M. furfur colonization. Although frequent adult handling may be a source, other aspects of intensive care will require careful scrutiny to define more completely the risk factors leading to M. furfur colonization of ill infants.

Ceftriaxone Kinetics and Cerebrospinal Fluid Penetration in Infants and Children with Meningitis

20 patients (0.4-5.6 years old) receiving ceftriaxone for the treatment of bacterial meningitis were studied. Simultaneous serum and cerebrospinal fluid concentrations of ceftriaxone were determined by HPLC in 15 patients at 11.4-12.8 h after an intravenous loading dose of 75 mg/kg. Serum and cerebrospinal fluid concentrations ranged from 20.5 to 44.9 (31.3 +/- 7.8) and from 1.1 to 8.0 (3.7 +/- 1.8) micrograms/ml, respectively. Cerebrospinal fluid concentrations ranged from 3 to 25% (12 +/- 6%) of the simultaneous serum concentrations. In 6 patients, serum and cerebrospinal fluid concentrations were determined after maintenance doses of 50 mg/kg/12 h. Serum and cerebrospinal fluid concentrations ranged from 120 to 144 and 2.3-4.9 micrograms/ml at 1.8-5.5 h after the first maintenance dose in 2 patients; 74-139 and 5.7-7.9 micrograms/ml at 1.3-5.8 h after the second dose in 3 patients and was 101 and 4.1 micrograms/ml at 4 h after the 3rd dose in 1 patient. Multiple blood samples were collected after the loading dose in 5 patients and after 9-10 days of maintenance doses in 3 patients. Steady-state peak and trough serum concentrations ranged from 295 to 440 and 32.6-44.8 micrograms/ml, respectively. After the loading and maintenance dose at steady-state, total body clearance averaged 1.17 and 0.64 ml/min (p = 0.01); apparent volume of distribution averaged 0.37 and 0.26 l/kg (p greater than 0.05); and elimination half-life averaged 3.7 and 4.6 h (p = 0.01), respectively. These results suggest that (1) adequate cerebrospinal fluid concentrations of ceftriaxone can be achieved in patients with meningitis with the dosage regimen studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Scanning electron microscopy of Malassezia furfur attachment to broviac catheters

Malassezia furfur has been increasingly associated with Broviac-catheter-related sepsis in infants receiving fat emulsions for parenteral alimentation. We examined by scanning electron microscopy the appearance of M. furfur attached to Broviac catheter segments mock-infected in vitro and to Broviac catheters removed from two infants with catheter-related sepsis. In vitro attachment occurred equally on external and internal surfaces of the catheters. Although some organisms were attached next to surface defects in the catheters, we could not determine if such defects were preferential sites of attachment. In the patient catheters, a dense coating of yeast cells was found adhering to the luminal surface, most abundantly near the tip. No organisms were seen on the external surface of the catheters. These findings show the need to examine the mechanisms of intraluminal catheter colonization in order to understand better the pathogenesis of M. furfur infections.

Moxalactam epimer kinetics in children

The kinetics of the R and S epimers of moxalactam were followed after single intravenous doses of 50 mg/kg to 12 patients, 8 to 45 mo old, with cellulitis or epiglottitis. High‐pressure liquid chromatography was used to determine serum concentrations. Total body clearance and apparent volume of distribution of the R epimer were higher than those of the S epimer (P < 0.004). Total body clearance of R, S, and R + S moxalactam ranged from 29.01 to 183.7, 19.00 to 79.95, and 23.34 to 113.6 ml/min/m2. Mean elimination half‐lives of R, S, and R + S moxalactam were 2.04, 2.26, and 2.24 hr. The higher clearance of the more active R epimer and the 500% interpatient variation in clearance may indicate a need for monitoring serum and cerebrospinal fluid concentrations in patients with severe unresponsive central nervous system infections treated with moxalactam.

Intrapatient variation in tobramycin kinetics in low birth weight infants during first postnatal week

SummaryNineteen newborn infants receiving tobramycin, 2.5 mg/kg every 12 h were studied on two occasions at steady-state during the first week of postnatal age. The two studies were separated by two to four days. Total body clearance of tobramycin averaged 1.15 and 1.14 ml/min/kg (p>0.05), apparent volume of distribution averaged 0.82 and 0.68 l/kg (p>0.05), and elimination half-life averaged 8.6 and 7.1 h (p>0.05), during the first and second study, respectively. When the data were further analyzed based on the birth weight, tobramycin kinetics changed during the second study compared to the first study in very low birth weight infants. In eight infants ⩽1.5 kg birth weight, although total clearance of tobramycin was similar, the average apparent volume of distribution decreased from 1.04 l/kg during the first study to 0.73 l/kg during the second study (p<0.05) and elimination half-life from 11.1 h during the first study to 8.7 h during the second study (p<0.05). These data indicate that these infants may require a change in dosing interval with continued tobramycin therapy during the first week of postnatal age. Intrapatient variation in tobramycin kinetics should be considered, in addition to the interpatient variation reported previously, when monitoring the serum concentration to individualize tobramycin therapy in newborn infants ⩽1.5 kg birth weight.

Tobramycin pharmacokinetics in premature identical twins during newborn period.

Tobramycin is frequently used in premature infants but little is known about its pharmacokinetics in identical twins during the newborn period. We studied 6 twin infants (gestational age 29-31 weeks; postnatal age 3-4 days; birth weight 1.0-1.3 kg) receiving tobramycin 2.5 mg/kg i.v. over 20 min every 12-18 h. Steady-state peak and trough serum concentrations of tobramycin were in the range of 5.3-8.4 and 1.2-2.0 micrograms/ml, respectively. Total clearance (ClT) ranged from 0.74 to 1.19 ml/min/kg, distribution volume (V) from 0.74 to 0.94 liter/kg, and elimination half-life (t1/2) from 8.2 to 12.8 h. Comparison of data between infants in three identical twin pairs showed that despite a similar infusion method: (a) the time to achieve peak serum concentration ranged from 0.5 to 2.0 h; (b) the peak and trough concentrations normalized for dose varied from 0 to 50%, and (c) the ClT, V and t1/2 varied from 3 to 20%. These data should be considered in therapeutic drug monitoring of tobramycin in premature, identical twins during the newborn period.

Stability of Caffeine Injection in Intravenous Admixtures and Parenteral Nutrition Solutions

Our objective was to determine the stability of caffeine base in intravenous admixtures and parenteral nutrition solutions at room temperature for 24 hours. Caffeine 10 mg/mL was used in this study. The admixtures included D5W; D5W with NaCl 0.2% injection; D5W with NaCl 0.2% and 20 mEq/L of potassium chloride injection; D10W injection; and D10W with NaCl 0.2% and 5 mEq/L of KCl injection. The parenteral nutrition solutions included 1.1% amino acids with electrolytes; 2.2% amino acids with electrolytes; and 4.25% amino acids with electrolytes. These parenteral nutrition solutions were prepared in D10W. Ten milliliters of caffeine were added to glass test tubes containing 10 mL of various solutions to yield a final concentration of 5 mg/mL. One milliliter aliquots were removed at 0, 2, 4, 8, and 24 hours and caffeine was measured by a stability-indicating HPLC method. The largest change in the concentrations of caffeine was 4.1 percent during the study period. Thus, caffeine injection is stable in various admixtures and parenteral nutrition solutions at room temperature for 24 hours.

CEFTRIAXONE |[lpar]|CTX|[rpar]| KINETICS AND CEREBROSPINAL FLUID |[lpar]|CSF|[rpar]| CONCENTRATIONS IN INFANTS AFTER LOADING |[lpar]|LD|[rpar]| AND MAINTENANCE DOSES |[lpar]|MD|[rpar]|

Thirteen infants (0.4-1.4 yrs) with meningitis were studied. CTX therapy consisted of a 75 mg/kg LD, followed by 50 mg/kg MD every 12 hrs IV over 10 minutes. Simultaneous blood and CSF samples were obtained in 11 infants at 11.5-12.8 hr after LD. In 3 of these, multiple blood samples were collected after the LD and after 9-10 days of MD; simultaneous blood and CSF samples were also collected at 1.25-5.75 hr at steady-state. CTX was measured by HPLC. Simultaneous serum and CSF concentration ranged from 10.5-40.3 and 1.8-8.0 μg/ml after the loading dose and 74-139 and 5.8-7.9 μg/ml at steady-state, respectively. After LD and at steady-state, CTX total clearance was 1.06±0.18 and 0.64±0.06 ml/min/kg (P<0.05), distribution volume was 0.33±0.06 and 0.26±0.06 L/kg and elimination half-life was 3.67±0.06 and 4.61±0.28 hr, respectively. A higher CTX clearance at higher dose may be partly due to concentration-dependent plasma protein binding of CTX reported in adults. Although the CSF/serum concentration was low, the CSF bactericidal titers exceeded 1:512 suggesting a great potential for CTX therapy of central nervous system infections due to susceptible organisms.