Blood group AB increases risk for surgical necrotizing enterocolitis and focal intestinal perforation in preterm infants with very low birth weight.

Necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP) are two of the most common emergencies of the gastrointestinal tract in preterm infants with very low birth weight (VLBW, birth weight < 1500 g). Identification of risk factors among these children is crucial for earlier diagnosis and prompt intervention. In this study, we investigated a relationship between ABO blood groups and the risk for surgical NEC/FIP. We genotyped the ABO locus (rs8176746 and rs8176719) in VLBW infants enrolled in a prospective, population-based cohort study of the German Neonatal Network (GNN). Of the 10,257 VLBW infants, 441 (4.3%) had surgical NEC/FIP. In univariate analyses, the blood group AB was more prevalent in VLBW infants with surgical NEC/FIP compared to non-AB blood groups (OR 1.51, 95% CI 1.07-2.13, p = 0.017; absolute risk difference 2.01%, 95% CI 0.06-3.96%). The association between blood group AB and surgical NEC/FIP was observed in a multivariable logistic regression model (OR of 1.58, 95% CI 1.10-2.26, p = 0.013) as well. In summary, our study suggests that the risk of surgical NEC and FIP is higher in patients with blood group AB and lower in those having non-AB blood groups.

Fatty acid composition of adipose tissue at term indicates deficiency of arachidonic and docosahexaenoic acid and excessive linoleic acid supply in preterm infants.

BACKGROUND: Arachidonic (ARA) and docosahexaenoic acid (DHA) are constitutive to membrane phospholipids, and essential for brain and overall development. ARA/DHA pools in term infants (TI) are built during the third trimester, stored as adipose tissue triglycerides and predominantly distributed via plasma phosphatidylcholine (PC). In preterm infants (PTI), placental ARA/DHA supply is replaced by linoleic-acid (LA)-enriched nutrition. This study aimed to investigate the impact of PTI nutrition, compared to placental supply, on fatty acid composition in adipose tissue and blood. METHODS: Prospective observational study (4/2017-3/2019) in 12 PTI and 3 PTI with enterostomy (PTI/E) (gestational age (GA) < 32 weeks) with surgical intervention at term (± 6 weeks) and 14 TI (GA ≥ 34 weeks, surgical intervention < 2 weeks postnatally). PTI/E were analyzed descriptively only. PC and triglyceride fatty acids were analyzed with tandem mass spectrometry and gas chromatography, respectively. Results were compared between TI and PTI with Wilcoxon Test and shown as median [25th percentile-75th percentile] mol%. RESULTS: PTI had less ARA in adipose tissue TG (0.77[0.67-0.87]% vs. 1.04[0.95-1.14]%, p = 0.0003) and plasma PC (20.7[18.7-22.8]% vs. 28.3[22.7-33.5]%, p = 0.011) than TI. PTI also had less DHA in adipose tissue TG (0.6[0.4-0.8]% vs. 1.1[0.8-1.4]%, p = 0.006) and plasma PC (6.4[5.6-7.1]% vs. 8.4[7.8-13.1]%, p = 0.002). LA was increased in PTI's adipose tissue TG (10.0[8.8-12.3]% vs. 3.0[2.5-3.6]%, p < 0.0001) and plasma PC (48.4[44.6-49.6]% vs. 30.6[24.9-35.6]%, p = 0.0002). Similar differences were observed in erythrocyte PC. CONCLUSION: In PTI, LA is increased and ARA/DHA decreased in adipose tissue, plasma and erythrocyte lipids as proxies for other tissues, likely caused by PTI nutrition. This may contribute to impaired PTI development.

Healthy term and moderately preterm infants have similar cerebral oxygen saturation and cerebral blood flow volumes during early post-natal transition.

AIM: This pilot study evaluated changes in regional cerebral oxygen saturation and cerebral blood flow volume during the transitional period in healthy term and moderately preterm infants. METHODS: The cohort comprised 16 preterm infants and seven full-term infants with mean gestational ages of 34 and 39 weeks, respectively. Longitudinal measurements were conducted during the first three days after birth. Regional cerebral oxygen saturation was determined bilaterally by frequency domain near-infrared spectroscopy. Flow volumes were determined in internal carotid and vertebral arteries by multiplying the time-averaged velocity by the cross-sectional area: cerebral blood flow volume was calculated as the sum of flow volumes and adjusted for brain weight. RESULTS: Brain weight-adjusted cerebral blood flow volumes and regional cerebral oxygen saturation were similar in preterm and term infants. Regional cerebral oxygen saturation did not correlate with brain weight-adjusted cerebral blood flow volume. Right and left brain weight-adjusted internal carotid flow volumes did not correlate with right and left regional cerebral oxygen saturation. CONCLUSION: Our findings suggest that during the first three days after birth there was adequate cardiorespiratory adaptation, cerebral perfusion and adequate compensation through the arterial circle of Willis in both healthy term and moderately preterm infants.

A historic cohort study on accelerated advancement of enteral feeding volumes in very premature infants.

BACKGROUND: The optimal rate of enteral feeding (EF) advancement in very low birth weight infants is under debate. OBJECTIVES: To evaluate the effects of accelerated EF advancement on the time to full enteral feeds, on early postnatal growth as well as on the frequency of necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP) in very premature infants. METHODS: In a retrospective single-center historic cohort study, infants with a gestational age <32 weeks at birth and birth weight <1,500 g, born between January 1, 2006, and December 31, 2007 (n = 136), were compared with infants born between January 1, 2010, and December 31, 2010 (n = 88). In 2006/2007, enteral feeds were initiated on day 1 with 10-15 ml/kg/day and advanced by 15-20 ml/kg/day. In 2010, enteral feeds were initiated with 20 ml/kg/day on day 1 and advanced by 25-30 ml/kg/day. Full enteral feeds were defined as ≥ 140 ml/kg/day. Data are presented as median (P25-P75). RESULTS: The time to establish full enteral feeds was shorter in 2010: 8 (7-11) days in 2006/2007 versus 6 (5-9) days in 2010. The incidences of NEC and FIP were 2.7 and 4.1% in 2006/2007 and 3.3 and 2.2% in 2010, respectively. Weight gain was not affected by the rate of EF advancement. Higher parenteral protein intake during week 1 in 2006/2007 was associated with better head circumference growth. CONCLUSIONS: The new approach was associated with a significantly shorter period to establish full enteral feeds. No difference in the incidence of FIP or NEC was observed; however, the study was underpowered to detect small but possibly important differences.

[Prevention of bone mineral deficiency in premature infants: review of the literature with focus on monitoring of urinary calcium and phosphate]. / Knochenmineralmangel bei Frühgeborenen: Prävention mittels Urinmonitoring von Kalzium und Phosphat.

BACKGROUND: Bone mineral deficiency of prematurity (BMDoP) is caused by the lack of simultaneous availability of calcium (Ca) and anorganic phosphate (P) during rapid skeletal growth. METHODS: Review of the literature on the prevention of BMDoP, with specific attention to the limitations of the monitoring of urinary calcium and phosphate concentrations. RESULTS: Intrauterine bone mineral accretion (BMA) can be achieved in preterm infants if urinary concentrations of Ca and P continuously show that the supplementation with these ions slightly exceeds the actual need. An individually adjusted supplementation with Ca and P appears rational because both growth velocity and enteral Ca absorption are highly variable and determine the need for enteral Ca and P administration. If, however, urinary concentrations of Ca and P are used to determine whether Ca and P supplementation is adequate, mechanisms affecting the urinary excretion of these ions other than nutrition have to be taken into account. Specifically, methylxanthines and diuretics increase the renal Ca losses, and the renal P threshold may be lowered in premature infants. A positive effect of physical activity on BMA has been shown in several studies. CONCLUSIONS: An individualized Ca and P supplementation in preterm infants aiming for supplementation in a slight excess of the actual need and guided by urinary Ca and P concentrations appears able to prevent BMDoP. Monitoring of urinary Ca and P concentrations needs to take into account non-nutritional factors affecting these concentrations. BMA may further be improved by physical activity.

Histopathology and the lethal effect of Cry proteins and strains of Bacillus thuringiensis Berliner in Spodoptera frugiperda J.E. Smith Caterpillars (Lepidoptera, Noctuidae).

Among the phytophagous insects which attack crops, the fall armyworm, Spodoptera frugiperda (J.E. Smith, 1797) (Lepidoptera, Noctuidae) is particularly harmful in the initial growth phase of rice plants. As a potential means of controlling this pest, and considering that the entomopathogen Bacillus thuringiensis Berliner demonstrates toxicity due to synthesis of the Cry protein, the present study was undertaken to evaluate this toxic effect of B. thuringiensis thuringiensis 407 (pH 408) and B. thuringiensis kurstaki HD-73 on S. frugiperda. The following method was used. Both bacterial strains were evaluated in vitro in 1st instar S. frugiperda caterpillars, by means of histopathological assays. The Cry1Ab and Cry1Ac proteins, codified by the respective strains of B. thuringiensis, were evaluated in vivo by bioassays of 1st instar S. frugiperda caterpillars in order to determine the Mean Lethal Concentration (LC50). The results of the histopathological analysis of the midget of S. frugiperda caterpillars demonstrate that treatment with the B. thuringiensis thuringiensis strain was more efficient, because the degradations of the microvilosities started 9 hours after treatment application (HAT), while in the B. thuringiensis kurstaki the same effect was noticed only after 12 HAT. Toxicity data of the Cry1Ab and Cry1Ac proteins presented for the target-species LC50 levels of 9.29 and 1.79 microgxcm-2 respectively. The strains and proteins synthesised by B. thuringiensis thuringiensis and B. thuringiensis kurstaki are effective in controlling S. frugiperda, and may be used to produce new biopesticides or the genes may be utilised in the genetic transformation of Oryza sativa L.

Histopathology and the lethal effect of Cry proteins and strains of Bacillus thuringiensis Berliner in Spodoptera frugiperda J.E. Smith Caterpillars (Lepidoptera, Noctuidae) / Histopatologia e efeito letal de cepas e proteínas Cry de Bacillus thuringiensis Berliner para lagartas de Spodoptera frugiperda J.E. Smith (Lepidoptera, Noctuidae)

Among the phytophagous insects which attack crops, the fall armyworm, Spodoptera frugiperda (J.E. Smith, 1797) (Lepidoptera, Noctuidae) is particularly harmful in the initial growth phase of rice plants. As a potential means of controlling this pest, and considering that the entomopathogen Bacillus thuringiensis Berliner demonstrates toxicity due to synthesis of the Cry protein, the present study was undertaken to evaluate this toxic effect of B. thuringiensis thuringiensis 407 (pH 408) and B. thuringiensis kurstaki HD-73 on S. frugiperda. The following method was used. Both bacterial strains were evaluated in vitro in 1st instar S. frugiperda caterpillars, by means of histopathological assays. The Cry1Ab and Cry1Ac proteins, codified by the respective strains of B. thuringiensis, were evaluated in vivo by bioassays of 1st instar S. frugiperda caterpillars in order to determine the Mean Lethal Concentration (LC50). The results of the histopathological analysis of the midget of S. frugiperda caterpillars demonstrate that treatment with the B. thuringiensis thuringiensis strain was more efficient, because the degradations of the microvilosities started 9 hours after treatment application (HAT), while in the B. thuringiensis kurstaki the same effect was noticed only after 12 HAT. Toxicity data of the Cry1Ab and Cry1Ac proteins presented for the target-species LC50 levels of 9.29 and 1.79 μg.cm-2 respectively. The strains and proteins synthesised by B. thuringiensis thuringiensis and B. thuringiensis kurstaki are effective in controlling S. frugiperda, and may be used to produce new biopesticides or the genes may be utilised in the genetic transformation of Oryza sativa L.

Entre os insetos fitófagos que atacam as culturas, Spodoptera frugiperda (J.E. Smith, 1797) (Lepidoptera, Noctuidae) destaca-se como uma praga polífaga que causa prejuízos na fase inicial da cultura do arroz. No seu controle, o entomopatógeno Bacillus thuringiensis Berliner revela-se tóxico devido à síntese de proteínas Cry. Nesse contexto, o objetivo deste trabalho foi avaliar a toxicidade das cepas e proteínas Cry de B. thuringiensis thuringiensis 407 (pH 408) e B. thuringiensis kurstaki HD-73 sobre S. frugiperda. As duas cepas bacterianas foram avaliadas, in vitro, em lagartas de 1º instar de S. frugiperda, através de ensaios de histopatologia. As proteínas Cry1Ab e Cry1Ac, codificadas pelas respectivas cepas de B. thuringiensis, foram avaliadas in vivo, através de bioensaios com lagartas de 1º instar de S. frugiperda para determinação da Concentração Letal Média (CL50). Os resultados da análise histopatológica do intestino médio das lagartas S. frugiperda mostram que o tratamento com a cepa B. thuringiensis thuringiensis foi mais eficiente e a degradação das microvilosidade iniciou-se 9 horas após a aplicação dos tratamentos (HAT). Para B. thuringiensis kurstaki, o mesmo efeito foi observado, 12 HAT. Os dados de toxicidade das proteínas de Cry1Ab e Cry1Ac revelaram para a espécie-alvo uma CL50 de 9,29 e 1,79 μg.cm-2, respectivamente. As cepas e proteínas sintetizadas por B. thuringiensis thuringiensis e B. thuringiensis kurstaki são eficientes no controle de S. frugiperda, e poderão ser usadas na produção de novos biopesticidas ou a utilização dos genes na transformação genética de Oryza sativa L.

Clinical characteristics of viral intestinal infection in preterm and term neonates.

The clinical presentation of the viral enteric pathogens in newborn infants has not been adequately examined. The aim of this study was to evaluate the clinical characteristics of viral intestinal infections in newborn infants. Clinical data of all term and preterm infants admitted to our tertiary neonatal intensive care unit from 1998 to 2007 with clinical signs of gastroenteritis (GE) or necrotizing enterocolitis (NEC) were retrospectively reviewed and compared between infants with different viral enteric pathogens in stool specimens. In 34 infants with signs of GE or NEC, enteropathogenic viruses were found in stool specimens. Rotavirus was detected in 12 cases, of which two infants had NEC. Compared with infants with rotavirus or norovirus, infants with astrovirus more frequently suffered from NEC (p<0.05). In addition, an acute systemic inflammatory response was significantly more common in patients with astrovirus infection (astrovirus vs. rotavirus and astrovirus vs. norovirus, p < 0.01 and p < 0.05, respectively). Of eight children infected with norovirus, one infant had a systemic acute inflammatory response and NEC. This study demonstrates that in newborn infants, intestinal rotavirus, norovirus, and astrovirus infections may be associated with severe illness such as hemorrhagic enteritis resulting in bloody diarrhea or even NEC.

Growth after intrauterine laser coagulation for twin-twin transfusion syndrome.

OBJECTIVE: The aim of this study was to investigate prenatal and postnatal growth of twins with twin-twin transfusion syndrome (TTTS) after intrauterine laser coagulation. STUDY DESIGN: The weight and length of 54 sets of twins with severe TTTS surviving intrauterine laser coagulation at the intervention (median 20+4 weeks), at birth (median 34+3 weeks) and on the occasion of neurodevelopmental follow-up (median age 3 years 10 months) were investigated. All data were converted to Z scores, and groups were compared by two-tailed paired t test. RESULTS: At all time points, donors are significantly lighter than recipients (p<0.001). After laser treatment the weight Z score of donors until birth remains unchanged (p=0.76), whereas recipients lose weight significantly (p<0.01). Postnatally, both donors and recipients show catch-up growth. CONCLUSION: Intrauterine laser coagulation stops growth acceleration in recipients that leads to a decrease in intertwin discordance. After birth, significant catch-up growth was observed for the donor group (p<0.001).

Rational approach to the diagnosis of severe growth hormone deficiency in the newborn.

CONTEXT: Severe congenital GH deficiency (GHD) of the newborn is a rare disease, which can cause life-threatening hypoglycemias beginning in the first week of life. Reviews and consensus papers on the diagnosis of GHD repeatedly state the lack of a practical evidence-based approach to the diagnosis of GHD in the newborn. OBJECTIVE: Here we provide for the first time sound reference values and a diagnostic cutoff for the GH levels in newborns at the age between d 3 and 5. DESIGN, SETTING, AND PATIENTS: GH was measured in the eluate from 314 filter papers of the newborn screening test performed in our university hospital by using a highly sensitive human GH-ELISA. Reference data are compared with measurements from nine newborns with very high likelihood of having severe GHD, and cutoffs for the diagnostic work-up are defined. RESULTS: In the presence of clinical evidence, the diagnosis of neonatal GHD can be confirmed during the first week of life by a single randomly taken GH level less than 7 microg/liter with 100% sensitivity and 98% specificity on the basis of our assay method. GH content in newborn screening cards stored for almost 3 yr were not different from the content found in recently used screening cards indicating high immunological stability of GH over time. Therefore, the diagnostic approach can use stored screening cards. In addition, we observed a clear gender dichotomy in respect to GH, with healthy female newborns having significantly higher GH levels than males. Cigarette smoking during pregnancy was associated with higher, transient tachypnea of the newborn with lower GH levels. CONCLUSIONS: We provide the first rational approach to the diagnosis of severe GHD in the newborn and evidence for gender dichotomy of the neonatal GH axis.

Pyridoxal phosphate-dependent neonatal epileptic encephalopathy.

Pyridox(am)ine-5'-phosphate oxidase converts pyridoxine phosphate and pyridoxamine phosphate to pyridoxal phosphate, a cofactor in many metabolic reactions, including neurotransmitter synthesis. A family with a mutation in the pyridox(am)ine-5'-phosphate oxidase gene presenting with neonatal seizures unresponsive to pyridoxine and anticonvulsant treatment but responsive to pyridoxal phosphate is described. Pyridoxal phosphate should be considered in neonatal epileptic encephalopathy unresponsive to pyridoxine.

Pyridoxal phosphate-dependent neonatal epileptic encephalopathy.

Pyridox(am)ine-5'-phosphate oxidase converts pyridoxine phosphate and pyridoxamine phosphate to pyridoxal phosphate, a cofactor in many metabolic reactions, including neurotransmitter synthesis. A family with a mutation in the pyridox(am)ine-5'-phosphate oxidase gene presenting with neonatal seizures unresponsive to pyridoxine and anticonvulsant treatment but responsive to pyridoxal phosphate is described. Pyridoxal phosphate should be considered in neonatal epileptic encephalopathy unresponsive to pyridoxine.

Oral valganciclovir for symptomatic congenital cytomegalovirus infection in an extremely low birth weight infant.

Cytomegalovirus (CMV) infection is the most important congenital viral infection. Intravenous (i.v.) Ganciclovir (GCV) improved outcome in term infants with symptomatic congenital CMV infection. We present data on oral valganciclovir (VGCV) in an extremely low birth weight infant. A male preterm infant was delivered at 28 weeks of gestation because of abnormal fetal perfusion with severe intrauterine growth retardation. The infant developed hepatitis and a severe thrombocytopenia. Serology revealed a positive CMV IgM in maternal serum 3 days after delivery and CMV DNA was detected in plasma and urine samples of the infants. Treatment with i.v. GCV was started at day 4 of life for 35 days and continued with oral VGCV for further 6 weeks. Plasma GCV levels were 1.68 ng ml(-1) (peak) and 0.92 ng ml(-1) (trough) on day 10 of oral treatment. Clinical signs resolved and virus load decreased slowly during therapy. At discharge brain stem-evoked audiometry was normal. Oral treatment with VGCV in an extremely low birth weight preterm infant with congenital CMV infection resulted in adequate GCV plasma levels, reduced effectively the CMV viral load and was well tolerated without apparent adverse effects.

Pyridoxal 5'-phosphate may be curative in early-onset epileptic encephalopathy.

Neonatal epileptic encephalopathy can be caused by inborn errors of metabolism. These conditions are often unresponsive to treatment with conventional antiepileptic drugs. Six children with pyridox(am)ine-5'-phosphate oxidase (PNPO) deficiency presented with neonatal epileptic encephalopathy. Two were treated with pyridoxal 5'-phosphate (PLP) within the first month of life and showed normal development or moderate psychomotor retardation thereafter. Four children with late or no treatment died or showed severe mental handicap. All of the children showed atypical biochemical findings. Prompt treatment with PLP in all neonates and infants with epileptic encephalopathy should become mandatory, permitting normal development in at least some of those affected with PNPO deficiency.

Hydrolysis of casein accelerates gastrointestinal transit via reduction of opioid receptor agonists released from casein in rats.

BACKGROUND: Protein hydrolysate accelerates gastrointestinal transit (GIT) and feeding advancement in preterm infants compared to native protein. In rat pups, opioid receptor agonists released from casein during digestion such as beta-casomorphins slow down GIT. We hypothesized that hydrolysis of casein reduces the opioid activity released during digestion thereby accelerating GIT compared to native casein. OBJECTIVE: The aim of the present study was to investigate whether casein hydrolysate accelerates GIT compared to native casein and whether pretreatment with naloxone, an opioid receptor blocker, abolishes this difference in rat pups. METHODS: In a randomized controlled trial following a 2 x 2 factorial design, 216 female Wistar rat pups were fed with pellets based on hydrolyzed or native casein. After pretreatment with naloxone or normal saline, carmine red was administered by oro-gastric gavage as a tracer for GIT velocity measurement. Four hours later the animals were sacrificed, their intestine was removed and the length of the colon from the cecocolonic junction to the anus was measured. GIT was recorded as percentage of the total colonic length (percentage of colonic transit) passed by carmine red. Data were given as mean +/- SD. RESULTS: GIT was significantly higher with hydrolyzed casein compared to native casein formula (77.4 +/- 17 and 51.2 +/- 20%), but there was no difference after naloxone pretreatment (77.1 +/- 16 and 76.5 +/- 17%). DISCUSSION: The present data suggest that hydrolysis of casein accelerates GIT via reduction of opioid activity released during digestion. Further studies are required to investigate to which extent these rat pub data apply to preterm infants.

Transcutaneous bilirubinometry in very low birthweight infants.

AIM: To evaluate whether transcutaneous bilirubinometry (TcB) would be a reliable and efficient screening technique for hyperbilirubinaemia in very low birthweight (VLBW, < or =1500 g) infants in an intensive care unit setting. METHODS: TcB measurements (Minolta Airshield Jaundice Meter JM-102, Osaka, Japan) were obtained immediately before or within 10 min following routine blood sampling for plasma bilirubin concentration measurements in 124 VLBW infants not receiving phototherapy. The relationship between the two techniques was analysed by linear regression analysis. A plasma bilirubin > or =150 micromol/l was defined as hyperbilirubinaemia. The sensitivity and specificity of possible TcB cut-off readings to detect hyperbilirubinaemia was evaluated. RESULTS: There was a significant correlation between the measurements of both techniques (p < 0.0001, r = 0.68). In the present study, a TcB cut-off reading of 14 would have reduced the need for plasma bilirubin measurements by 26% without missing true hyperbilirubinaemia. CONCLUSION: The data suggest that TcB will improve VLBW infant care in an intensive care unit setting by reducing the need for invasive bilirubin concentration measurements.

Whole blood interleukin 8 and plasma interleukin 8 levels in newborn infants with suspected bacterial infection.

AIM: To evaluate a new micro-method technique for measurement of interleukin 8 in detergent-lysed whole blood (whole blood IL-8) applicable to capillary blood sampling as a test for bacterial infections in neonates. METHODS: Whole blood IL-8 was measured at the first suspicion of infection along with IL-8 determined in plasma (plasma IL-8), C-reactive protein and blood cultures in 154 consecutive newborn infants with clinical signs of bacterial infection. Only 20 microl of whole blood were required for the new assay. RESULTS: Blood culture-proven infections were diagnosed in six infants and clinical infection (defined as a combination of clinical and laboratory signs) in 20 infants. 1000 pg/ml was determined as the suitable threshold for whole blood IL-8 by ROC-curve analysis. At that threshold, whole blood IL-8 detected blood culture-proven infections with a sensitivity of 83% and a specificity of 67%. The areas under the ROC curves were similar for whole blood IL-8 and plasma IL-8. CONCLUSIONS: Compared with plasma IL-8, whole blood IL-8 offers the advantages that measurements of whole blood IL-8 require a smaller blood sample volume and are not altered by haemolysis. The diagnostic accuracy of whole blood IL-8 remains to be studied in more detail in the future.

Pulmonary administration of perfluorodecaline- gentamicin and perfluorodecaline- vancomycin emulsions.

The aim of this study was to examine pharmacokinetics and pulmonary antibiotic tissue concentrations (PATC) of gentamicin and vancomycin after intrapulmonary administration of a perfluorodecaline (PFD)-gentamicin and a PFD-vancomycin emulsion during partial liquid ventilation (PLV). PLV was initiated in 19 healthy rabbits and 18 surfactant-depleted rabbits. The animals were randomized to receive either 5 mg/kg gentamicin and 15 mg/kg vancomycin intravenously, or 5 mg/kg gentamicin intrapulmonary, or 15 mg/kg vancomycin intrapulmonary. Antibiotic plasma levels were measured after 15, 30, 45, and 60 min, and hourly thereafter. After 5 h animals were sacrificed and lungs were removed to evaluate PATC and histology. PATC were significantly higher after intrapulmonary administration of both gentamicin and vancomycin. In healthy rabbits, peak plasma concentrations were lower and 5 h plasma concentrations were higher after intrapulmonary administration, whereas plasma concentrations were not different in surfactant-depleted rabbits. There were no differences in lung histology, hemodynamics, lung mechanics, or gas exchange between the treatment groups. We conclude that during PLV, higher PATC can be achieved after intrapulmonary administration of PFD-antibiotic emulsions compared with intravenous administration of the same dose without apparent short-term adverse effects. We speculate that intrapulmonary antibiotic administration during PLV may be beneficial in treating severe pneumonia.