FED-UP PHAGOCYTES: SPLENIC MACROPHAGE FUNCTION IN 1051 GAUCHERsS DISEASE. Peter E. Newburger, and Susan L. Hansen. (Spon. by David G. Nathan). Harvard Medical School, children's Hospital, Division of Hematology, Boston, MA. In ordcr to tcst thc phagocytic function of reticuloendothelial cells in storage diseases, we compared the ingestion and respira- tory burst capacities of splenic macrophages (M0) from a patient with Gaucher's disease to control splenic M0 from patientsltith Stage IA or IIA Hodgkin's disease. Gaucher (M0) ingested C-lab- eled E. coli at a rate 22% that of control M0 but bound the E. c o l i 75%?well as controls. We measured respiratory burst ac- - tivity in pooled cells by a continuous spectrophotometric assay of superoxide (02) production in individual cells by nitro-blue tetrazolium (NBT) slide tests. Both assays utilized phorbol myr- istate acetate (PMA) a soluble stimulant, or opsonjzed zymosan (OpZ) particles to initiate the respiratory burst. 0; production - NBT Stimulus nmol/min/lO~ cells % + cells Gaucher's PMA 2.41 OP 0.21 Control PMA 2.19 97 OP z 1.40 93 Thus Gaucher's disease splenic M0 engorged with cerebroside ex- hibit a defect not only in ingestion but also in their ability to activate the respiratory burst in response to complement-opsoniz- ed particles. However they bind particles nearly as well as controls and produce a normal respiratory burst response to a soluble stimulant. INHALED CEPHALORIDINE IN THE TREATMENT OF CYSTIC FIBROSIS (CF), G. Nolan, P. McIvor, R. Gold, C. Newth, H. Levison and M. Corey, Dept. of Pediatrics, The Hosp. for Sick Children, Toronto. The use of inhaled antibiotics in CF i s both controversial and expensive. However they are used in many centers. In order to assess the effect of prophylactic inhaled cephaloridine on the colonization of the respiratory tract with staphylococcus aureus and other pathogens and on the general progression of the disease we are following 47 patients with mild to moderate CF in a con- trolled prospective study. Patients are seen monthly for quan- titative sputum cultures and clinical assessment. Chest x-ray and pulmonary function testing are performed every 6 months. 25 patients receive daily inhaled cephaloridine, 22 patients do not receive any inhaled antibiotic. Both groups receive oral cloxacillin. The groups are balanced for age, sex and severity of the pulmonary disease. Analysis of the first 12 months of the study show that there are no differences in either Schwachman scores, chest x-ray, pulmonary function, incidence of respiratory infections, or quantitative sputum cultures. Over 90% of children carried Pseudomonas aeruginosa and 35% carried Pseudomonas cepacia regardless of treatment group. Only 8% of children in each group carried S. aureus. We conclude that antistaphylococcal prophylaxis with inhaled cephaloridine plus oral cloxacillin does not add any benefits to oral cloxacillin alone and is not indicated in the management of children with CF. EPIDEMIOLOGY OF NOSOCOMIAL INFECTIONS IN A NEWBORN 053 INTENSIVE CARE UNIT. J.C. Overall, Jr., S.D. Minton, G.M. Chan, A.K. Volkman, G.Stoddard & J.J. Sullivan, Department of Pediatrics in the University of Utah College of Medicine and the College of Nursing, Salt Lake City, Utah. Nosocomial infections (NI) are a known problem in newborn in- tensive care units (NBICU), but important predisposing factors are not clearly defined. Prospective surveillance for NI risk factors was conducted on all newborns admitted to the Utah NRICU longer than 48 hrs (at risk for NI) during a 6-month period. Twenty-five of 175 (14.3%) patients developed 52 NI, a NI rate of 29,7%. The most common f i r s t NI were pneumonia (13 or 52%) and necrotizina enterocolitis (7 or 28%). The 25 NI infants had a higher uiderlying disease severity score during the first 24 hrs after admission than the 150 non-NI babies (mean score of 5,4 vs 4.2 out of a scale of 8, p=.001). NI infants had a grea- ter number of procedures than non-NI infants during the first week of hospitalization: 1) endotracheal tube days (mean of 5.6 vs 3.9, p=.007); 2) umbilical artery catheter (UAC) days (mean of 5.4 vs 3.8, pz.01); and 3) combined UAC and heel stick blood samples (mean of 125.5 vs 98.4, p=.008). The same signi- ficant associations were observed with the 13 NI pneumonia pa- tients vs the non-NI infants. In addition, the 13 NI pneumonia cases had more endotracheal tube days than matched-control in- fants (mean of 5.7 vs 1.2, p=,03) during the 7 days prior to their first NI. These results indicate a significant associa- tion between underlying disease severity and the frequency of certain procedures and NI i n NBICU i n f a n t s . INFLUENCE OF INOCULUM SIZE ON INTERPRETATION OF SUS- 1054 CEPTIBILITY TESTING OF HAEMOPHILUS INFLUENZAE: MOXA- LACTAM VS. AMPICILLIN. Steven W. Parmelee, James K. Todd. C. Henry Kempe Center for Investigative Pediatrics, The Children's Hospital, Denver. A direct relationship between inoculum size and in vitro anti- biotic susceptibility is readily apparent in the response of Haemo hilus influenzae to beta-lactamase antibiotics. We studied t h r e e k n m f l u e n z a e , (Amps ~ h l o r o s ,A ~ P R ~ h l o r o s ,and AmpR ChloroR) in parallel under varying inocula conditions against Moxalactam and Ampicillin. The Amps s t r a i n showed l i t t l e or no inoculum effect with Moxalactam or Ampicillin while the AmpR strains showed dramatic differences in response to Ampicil- lin but not Moxalactam as demonstrated by broth dilution, agar dilution, and disk diffusion techniques. The inoculum effect was found to be independently related to the total number of colony- forming units (CFU) inoculated as well as the density of organ- isms (CFUIml). Kinetic studies demonstrated significant differ- ences between conventional broth growth curves and a continuous antibiotic flow system. Beta-lactamase producing g. influenzae reduced Ampicillin concentrations in "stagnant" in vitro systems but not in dynamic systems more analogous to the steady state of patients. Extrapolation from in vitro susceptibility studies to therapeutic decision-making requires knowledge beyond the MIC of an organism at a standard inoculum size, including: the total number of organisms in a patient, the maximum concentration of organisms in a patient, antibiotic tissue penetration, anti- biotic turnover, and the effect of host defenses. EMERGENCE OF MULTIPLY RESISTANT PNEUMOCOCCUS. Michael S. Radetsk , Mary P. Glode, Greg R. I s t r e (CDC, EIS a f i c e r ) , i r i a n A. Lauer, Andrew M. Wiesenthal. (Spon. by James K. Todd). C. Henry Kempe Center for Investiga- tive Pediatrics, The Children's Hospital, Denver. A strain of 2. pneumoniae resistant to multiple antibiotics was isolated from an 11-month-old infant with meningitis. CSF obtained after 96 hours of high-dose penicillin-G continued to grow a beta-lactamase negative pneumococcus, type 6. When t r e a t - ment was changed to ampicillin, chloramphenicol, and rifampin, the child improved; and CSF was sterile within 24 hours. Agar dilution MIC's were: pen-G 1 pg/ml; chloro, 16 pg/ml; ampicillin 0.5 pg/ml; tetracycline, 16 yg/ml; rifampin, 0.03 pg/ml. A cul- tural survey of day-care cdnter contacts utilized two selective media; one containing pen-G, 0.125 pg/ml, the other chloro, 4.0 ug/ml. 4/14 children <2 years and 5/47 older children and staff had throat carriage of this resistant strain, as did 5/10 of the family contacts of carriers. No carriers were treated. We also cultured 103 children in 4 other day-care centers without detect- ing the organism. We believe this to be the first report of a penicillin/chloramphenicol resistant pneumococcus in the Western Hemisphere. Due to the seriousness of delaying correct antibio- tic hrapy, we suggest that significant pneumococcal isolates be screened for both penicillin and chloramphenicol susceptibility. Surveys of contacts, which may yield a high carriage rate, can be performed rapidly using selective media. However, there is no established strategy regarding the treatment and follow-up of carriers. GRANULOCYTE ADHERENCE IN NEWBORN INFANTS: Sudha Rao 1056 Raymond L. Olesinski, Usha V. Doshi and ~ h a r m a p u ~ ' Vid asa ar. Abraham Lincoln School of Medicine, University o d k h H o s p i t a 1 , Department of Pediatrics , Chicago. Adherence to the vascular endothelium is an important cell property of the granulocyte which influences the degree of inflammation and host defense against bacterial invasion. In order to determine if granulocyte adherence (GA) is altered dur- ing the newborn period, we studied 52 full-term healthy neonates during their first week of life. The neonates were chosen from mothers who had uncomplicated pregnancies and were receiving no antenatal medications. All neonates had received 1 mg of Vitamin K intramuscularly after birth. GA was assayed by modified nylon fiber columns. The mean GA f SEM for 80 healthy adult volunteers was 69.6 ? 1.2% while the GA for the 52 newborns was 92.0 + 0.9%. There was a significant difference between the two populations (p< 0.01). There was no significant influence of either race or sex in both adult and neonatal populations studied. A small but significant negative correlation between GA and hematocrit existed for the adults (r= -0.242, p< 0.05) but no such correla- tion was demonstrable for the neonatal group. There was no sig- nificant correlation for the adults between GA and total granu- locyte counts, and a small but significant negative correlation was noted for the neonates (r= -0.285, p < 0.05). It is thus con- cluded that granulocyte adherence is markedly enhanced in the newborn infant as compared to the adult; ~t is further speculated that such enhanced adherence t o the endothelium possibly contrib- utes to the defective chemotaxis seen in newborn infants.