Parenteral Nutrition Solutions Research Articles

Distribution, virulence attributes and antifungal susceptibility patterns ofCandida parapsilosiscomplex strains isolated from clinical samples

It was recently proposed that Candida parapsilosis represents a complex composed of three closely related species, i.e., C. parapsilosis sensu stricto, C. orthopsilosis, and C. metapsilosis. The aim of this study was to describe the distribution of C. parapsilosis complex isolates among clinical samples. We also evaluated antifungal susceptibility profiles, in vitro presence of lipase and secreted aspartyl proteinase, as well as their ability to grow in total parenteral nutrition (TPN) solution, and biofilm production. A total of 413 non-C. albicans Candida isolates were obtained from various clinical samples between 2010 and 2011 in a Turkish Tertiary Care Hospital. Of them, 42 were identified as members of the C. parapsilosis complex. Among these, 38 (90.5%) were C. parapsilosis sensu stricto, 3 (7.1%) C. metapsilosis, and 1 (2.4%) C. orthopsilosis. All isolates recovered from blood were found to be C. parapsilosis sensu stricto and C. metapsilosis. In phenotypic tests, all 42 isolates grew in TPN solution and, although 26.2% of C. parapsilosis sensu stricto-isolates were capable of forming biofilms in vitro, neither C. orthopsilosis nor C. metapsilosis isolates were able to do so. Acid proteinase activity was detected in 31% of isolates and lipase activity in 33%. All isolates were sensitive to voriconazole, caspofungin, and anidulafungin, with only a single C. parapsilosis sensu stricto isolate showing dose-dependent susceptible to fluconazole. While the number of C. metapsilosis and C. orthopsilosis isolates remained low, there were no significant differences in antifungal MIC as compared to C. parapsilosis sensu stricto.

Effect of parenteral nutrition solutions on biofilm formation of coagulase-negative Staphylococci: An experimental study

Objectives: In our study we investigated the effects of parenteral nutrition (PN) solutions on Coagulase negative staphylococci (CoNS) biofilm production. Materials and methods: Thirty nine CoNS strains isolated from hemocultures and a reference strain (ATCC 12228 Staphylococcus epidermidis) were included. Bacterial dilutions were made in Tryptic Soy Broth (TSB). The experimental mediums were 1. Glucose, 2. Amino acid, 3. Lipid, 4. Glucose+ Amino acid+ lipid, 5. Glucose+ Amino acid, 6. Glucose+ Lipid, 7. Amino acid+ Lipid, and 8. Control (TSB). Biofilm formation was evaluated by “quantitative microdilution plaque test”. The values greater than cut off value are considered as positive. Biofilm positivity was divided into 3 groups (mild, moderate and intensive) and all other strains under cutoff value were accepted as negative. The numbers of biofilm positive strains derived from 1-7. mediums were compared with each other, and with the results of control. Results: The three-component PN solution and two component PN solutions containing glucose+ lipid and amino acid+ lipid were found to increase the biofilm production activity of CoNS when compared to the control group. Slime positivity in medium 1 and 2 was lower than control significantly, in medium 4, 6, and 7 slime positivity was higher considerably. The indifferent results were obtained within the mediums 1, 2, 3 and within the mediums 4, 5, 6, and 7. Conclusions: In our study, it was found that, glucose, amino acid and lipid solutions which were building structures of PN decreased the biofilm production when used solitary. However use of the compounds increased the biofilm production. Therefore, we can conclude that PN solutions given as mixtures in routine practice increase the risk of catheter infection.

末梢静脈栄養(PPN)輸液の静脈炎惹起能の実験的検討

末梢静脈栄養(PPN)輸液の静脈炎惹起能の実験的検討

Aluminum exposure in neonatal patients using the least contaminated parenteral nutrition solution products.

Aluminum (Al) is a contaminant in all parenteral nutrition (PN) solution component products. Manufacturers currently label these products with the maximum Al content at the time of expiry. We recently published data to establish the actual measured concentration of Al in PN solution products prior to being compounded in the clinical setting [1]. The investigation assessed quantitative Al content of all available products used in the formulation of PN solutions. The objective of this study was to assess the Al exposure in neonatal patients using the least contaminated PN solutions and determine if it is possible to meet the FDA “safe limit” of less than 5 μg/kg/day of Al. The measured concentrations from our previous study were analyzed and the least contaminated products were identified. These concentrations were entered into our PN software and the least possible Al exposure was determined. A significant decrease (41%–44%) in the Al exposure in neonatal patients can be achieved using the least contaminated products, but the FDA “safe limit” of less than 5 μg/kg/day of Al was not met. However, minimizing the Al exposure may decrease the likelihood of developing Al toxicity from PN.

Anemia and Leukopenia in a Long‐Term Parenteral Nutrition Patient During a Shortage of Parenteral Trace Element Products in the United States

Recently, drug shortages in the United States have affected multiple components of the parenteral nutrition (PN) solution. A 62-year-old patient with systemic sclerosis who was dependent on home PN due to intestinal dysmotility developed anemia and leukopenia approximately 4 months after parenteral copper was withheld from her PN solution due to drug shortages. The patient was not able to tolerate a sufficient amount of oral multivitamins with trace elements due to severe dysphagia. Her serum copper and ceruloplasmin concentrations were undetectable, confirming the diagnosis of severe copper deficiency. The hematological abnormalities promptly resolved with copper supplementation. This report emphasizes the importance of close monitoring for nutrient deficiencies during drug shortages and supplementing with oral or enteral nutrition when feasible, particularly in high-risk patients such as those with intestinal malabsorption or short bowel syndrome who are dependent on long-term PN.

Management of Copper Deficiency in Cholestatic Infants

Copper is an essential trace element, playing a critical role in multiple functions in the body. Despite the necessity of adequate copper provision and data supporting the safety of copper administration during cholestasis, it remains common practice to reduce or remove copper in parenteral nutrition (PN) solutions after the development of cholestasis due to historical recommendations supporting this practice. In neonates, specifically premature infants, less is known about required copper intakes to accumulate copper stores and meet increased demands during rapid growth. Pediatric surgical patients are at high risk for hepatic injury during long-term PN provision and a balance is needed between the potential for reduced biliary excretion of copper and adequate copper intakes to prevent deficiency. Copper deficiency has been documented in several pediatric patients with cholestasis when parenteral copper was reduced or removed. Few data guide the management of copper deficiency in the pediatric population. The following case series describes our experience with successfully managing copper deficiency in 3 cholestatic infants after copper had been reduced or removed from their PN. Classic signs of copper deficiency were present, including hypocupremia, anemia, neutropenia, thrombocytopenia, and osteopenia. Treatment included use of both parenteral and enteral copper supplementation. We suggest revision of current recommendations regarding decreasing copper in PN during cholestasis with a proposed algorithm for parenteral copper provision in the setting of cholestasis that is based on evaluation of measured serum copper concentrations.

Urinary calcium excretion in short bowel syndrome patients receiving cyclic parenteral nutrition: Case report

ABSTRACTTotal parenteral nutrition is essential for the survival of short bowel syndrome patients. However, in the long term it is associated with complications such as metabolic bone disease. This complication has been attributed, among other causes, to an increased urinary calcium loss, which might be related to the amount of aminoacids, glucose and calcium present in the parenteral nutrition solution. Two case reports are here presented showing normal calciuria in short bowel syndrome adults, receiving parenteral nutrition for up to 5 years after extensive bowel resection.

Five-Year Evolution of Drug Prescribing in a University Adult Intensive Care Unit

Healthcare costs are steadily increasing. In Switzerland, in 2007, they amounted to 10.8% of gross domestic product, of which 45.6% related to hospital care (including drug-related costs) and 10.3% to drugs.[1] Very few data exist regarding evolution of drug costs in hospitals, as they are included in the hospital financing system.[2] In our university hospital, the 32-bed adult intensive care unit (AICU) amounts to 0.3% of hospital beds but 3% of hospital costs. In 2008, drug costs amounted to 4.8% of hospital costs but 11% of AICU costs. Intensive care physicians (ICPs) prescribe most usual drugs, but specialists clinicians (SCs) are allowed to prescribe specific expensive drugs in their specific field. We assessed the 5-year evolution of AICU drug prescription both in quantities and costs, by type of prescriber.Patients' characteristics and AICU activity were extracted from the 2004-2008 annual reports, and drug data were taken from the pharmacy database on a quarterly basis.First, global evolution of both quantities and costs of all drugs used in AICU was retrieved and split by the first level of the Anatomical Therapeutic Chemical (ATC) international system.[3] Then, within each ATC code, drugs with high consumption or high costs (yearly nominal values), or important variations over time in both quantities and costs, were singled out. Drugs with quarterly costs lower than 3000 Swiss francs (CHF) [[euro]2100, $US2300, 2008 values] were ignored. Finally, the share of both quantities and costs of drugs prescribed by SCs and ICPs were compared.Lastly, to account for annual inflation (0.6 to 1.2%) and increase in activity as measured by the number of admitted patients (2.2 to 7.3%), an adjusted daily cost of drug treatment was computed for each year of follow-up.Over the 5-year period, the number of AICU admissions increased by 10.8% (2226 to 2466), AICU days by 7.3% (9921 to 10 645), average length of stay by 5% (4.53 to 4.76 days), and occupancy rate by 8.0% (87% to 94%), while patients' severity did not significantly change. Over the same period, drug quantities increased by 36% (235 807 to 312 700 unit doses) and costs by 34% (CHF3 205 408 to CHF4 298 402), in a non-steady, non-parallel way (figure 1 displays the quarterly evolution of both drug quantities and costs).Fig. 1 Five-year evolution in drug quantities (solid line) and costs (dotted line), quarterly distribution. CHF = Swiss francs. [Figure omitted.]Four ATC classes amounted to 80% of both quantities and costs, with ATC code B (blood and haematopoietic organs) amounting to 63% of quantities and 41% of costs.In this class, the leading group in quantities and costs was B05 (blood substitutes and perfusion solutions). A peak in costs for B01 (anti-thrombotics), not mirrored in a peak in quantity, was noticeable in 2008, due to the temporary unavailability of danaparoid (B01AB09), replaced by argatroban (B01AE03), which was six times more expensive.Intravenous solutions (B05B) showed a major increase in costs of parenteral nutrition solutions, not mirrored in a corresponding increase in quantities, whereas the reverse was stated for intravenous electrolyte solutions. This transient increase was due to a shift towards prescribing more expensive solutions, which was reverted afterwards.A striking evolution was noted in antibiotics (ATC J01 CR05), when a generic for piperacillin tazobactam became available, resulting in important savings.Altogether, 48 drugs were identified which fulfilled the initial criteria of high quantity or costs or wide variations in quantities or costs. The detailed list is displayed in Annex 1 (Supplemental Digital Content, http://links.adisonline.com/APZ/A58).Prescription by the SCs amounted to an average of 1% in quantity, but 19% in costs. The rate of increase in both quantities and costs was seven times larger for ICPs than for SCs (figure 2 displays the quarterly evolution in drug prescription costs). …

The dose-dependent immunoregulatory effects of the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester in rats with sub-acute peritonitis.

BackgroundChronic inflammation accompanied by arginine deficiency, immune dysfunction, and excess nitric oxide (NO) production is a clinical condition found in patients with peritonitis. A previous study showed that the nonselective NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) may facilitate the metabolism of the immune nutrient arginine without altering NO homeostasis in rats with sub-acute peritonitis. Here, we investigated the effects of L-NAME on the immunocytic subpopulation distribution and response.Materials and MethodsMale Wistar rats with cecal puncture-induced peritonitis were administered parenteral nutrition solutions supplemented with 0 (CPP group), 5 (LNA group), 25 (MNA group) or 50 (HNA group) mg·kg−1·day−1 of L-NAME for 7 days. Parenteral-fed sham-operated rats (TPN group) and orally-fed healthy rats (R group) were included as controls.ResultsThe TPN group had significantly increased spleen weights and levels of plasma nitrite/nitrate (NOx), circulating white blood cells (WBC), and splenocytic T cells, as well as significantly decreased levels of cytotoxic T- and B-leukocytes and B-splenocytes compared to the R group. The CPP group had significantly decreased levels of plasma NOx and concanavalin (Con) A-stimulated interferon (IFN)-γ and interleukin (IL)-2 production by leukocytes and significantly increased production of Con A-stimulated tumor necrosis factor (TNF)-α and lipopolysaccharide (LPS)-stimulated IFN-γ in the leukocytes. In addition, the LNA and MNA groups had significantly decreased spontaneous IL-6 and Con A-stimulated TNF-α and IFN-γ production by the leukocytes while the HNA group had significantly increased LPS-stimulated TNF-α and Con A-stimulated IFN-γ and IL-2 production by the splenocytes compared to the CPP group.ConclusionsLow-dose L-NAME infusion may suppress proinflammatory and T-helper-1 (Th1) response in leukocytes, and high-dose infusion may activate the proinflammatory response in splenic macrophages and Th1 response in T-splenocytes in rats with sub-acute peritonitis.

Approach to Treatment of Hypophosphatemia

Hypophosphatemia can be acute or chronic. Acute hypophosphatemia with phosphate depletion is common in the hospital setting and results in significant morbidity and mortality. Chronic hypophosphatemia, often associated with genetic or acquired renal phosphate-wasting disorders, usually produces abnormal growth and rickets in children and osteomalacia in adults. Acute hypophosphatemia may be mild (phosphorus level, 2-2.5 mg/dL), moderate (1-1.9 mg/dL), or severe (<1 mg/dL) and commonly occurs in clinical settings such as refeeding, alcoholism, diabetic ketoacidosis, malnutrition/starvation, and after surgery (particularly after partial hepatectomy) and in the intensive care unit. Phosphate replacement can be given either orally, intravenously, intradialytically, or in total parenteral nutrition solutions. The rate and amount of replacement are empirically determined, and several algorithms are available. Treatment is tailored to symptoms, severity, anticipated duration of illness, and presence of comorbid conditions, such as kidney failure, volume overload, hypo- or hypercalcemia, hypo- or hyperkalemia, and acid-base status. Mild/moderate acute hypophosphatemia usually can be corrected with increased dietary phosphate or oral supplementation, but intravenous replacement generally is needed when significant comorbid conditions or severe hypophosphatemia with phosphate depletion exist. In chronic hypophosphatemia, standard treatment includes oral phosphate supplementation and active vitamin D. Future treatment for specific disorders associated with chronic hypophosphatemia may include cinacalcet, calcitonin, or dypyrimadole.

Neonatal Parenteral Nutrition Containing Calcium Chloride and Sodium Phosphate

Objective. The authors’ objectives were to determine mineral as well as Al intakes for ≤1000 g birth weight (ELBW) infants supported with parenteral nutrition (PN) solutions containing calcium chloride (CaCl) and sodium phosphate (NaPhos). Study design. This study was a prospective cohort study of 32 ELBW infants. Nutrient and Al intakes were recorded based on actual fluid intakes and concentrations of nutrients and Al in PN solutions. Growth velocities and peak alkaline phosphatase (AP) levels during the hospital stay were recorded. Result. Mean (±standard deviation) weight, length, and head circumference gains and AP were 13.7 ± 1.8 g/kg/d, 1.0 ± 0.2 cm/wk, 0.7 ± 0.1 cm/wk, and 636 ± 227 U/L, respectively. Al intake was 0.27 ± 0.07 µmol/kg/d (7.2 ± 1.8 µg/kg/d) in infants receiving PN with low Al content. This study documented average parenteral Ca and P intakes of 1.15 to 1.20 and 1.19 to 1.29 mmol/kg/d, (46-48 and 37-40 mg/kg/d), respectively, with PN fluid intakes of 90 to 100 mL/kg/d. Conclusion. AP and growth in ELBW infants receiving PN solutions containing CaCl are comparable to those reported in the literature for ELBW infants. Ca and P intakes approaching those reported for preterm infants receiving PN containing calcium gluconate can be provided with PN solutions containing CaCl. Fluid restriction is a significant factor limiting mineral intakes. Al intake can be limited to near FDA recommended intakes in PN solutions containing CaCl.

Early Chloride Intake Does Not Parallel That of Sodium in Extremely‐Low‐Birth‐Weight Infants and May Impair Neonatal Outcomes

Accurate data on the optimal chloride (Cl) intake in premature infants are scarce. The aim of the present study was to describe Cl intakes in the first 10 days of life and to assess the relations between high Cl intakes and corrected serum Cl level or markers of severe acidosis in infants <28 weeks' gestation. Retrospective cohort study including all of the infants <28 weeks admitted to the neonatal intensive care unit during a 3-year period and cared for from birth until day 10 or more. Fifty-six infants were included. Cumulative total Cl intakes reached 9.6 ± 3.7 mmol/kg at day 3 and 49.2 ± 13.5 mmol/kg at day 10. Inadvertent intakes (from intravenous fluids other than parenteral nutrition) represented on average 70% of total Cl intakes in the first 3 days. Difference between Cl and sodium intakes reached 7.8 ± 4.8 mmol/kg at day 10 and mainly originated from parenteral nutrition. By multivariate analysis, cumulative Cl intake >10 mmol/kg during the first 3 days was an independent risk factor of base excess <-10 mmol/L. Cumulative Cl intake >45 mmol/kg during the first 10 days was an independent risk factor of corrected chloremia >115 mmol/L and of base excess <-10 mmol/L. Cumulative Cl intake >10 mmol/kg during the first 3 days (ie, 3.3 mmol · kg (-1) · day(-1) on average) and >45 mmol/kg during the first 10 days (ie, 4.5 mmol · kg (-1) · day(-1) on average) may have unwanted metabolic consequences and should be avoided. Imbalance between electrolytes provided by the parenteral nutrition solution need to be detected and corrected.

Use of quantitative microbiological analyses to trace origin of contamination of parenteral nutrition solutions

In the summer of 2010, parenteral nutrition (PN) admixtures were administered to neonates in the Pediatric Department of the University Medical Center Mainz that provoked severe clinical sequelae. Contamination of a dummy infusion with Enterobacter cloacae and Escherichia hermannii was detected on the day of the incident, and the same isolates were subsequently grown from all PN admixtures as well as from the parent amino acid solution from which the admixtures had been prepared. Quantitative microbiological analyses paired with the determination of endotoxin concentrations enabled the conclusion to be reached that the amino acid solution had represented the primary source of contamination, which must have occurred in the distant past and may have derived from passage of the bacteria through a crack in the glass container. The findings have large implications, and the approaches employed should become of value when similar incidents occur again in the future.

The use of stability criteria for ìall in oneî parenteral nutrition solutions in paediatrics

BackgroundThe use of ‘all in one’ parenteral nutrition solutions (PNS) is supposed to reduce the problem of the instability of lipid emulsions, caused by the addition of different nutrients to...

Evaluation of the cost saving achieved by centralising total parenteral nutrition compounding

BackgroundTotal parenteral nutrition (TPN) solutions are usually prepared by centralised compounding in the Pharmacy Department.PurposeTo evaluate the cost saving achieved with centralised compounding of TPN solutions (newborns and adults) and...

Designing and implementing a standard nutritional starter solution for preterm infants

BackgroundAdministering parenteral nutrition to preterm infants in their first hours of life improves their survival. As it is not always possible for the pharmacy department to compound individual parenteral nutrition...

OHP031 Designing and implementing a standard nutritional starter solution for preterm infants

BackgroundAdministering parenteral nutrition to preterm infants in their first hours of life improves their survival. As it is not always possible for the pharmacy department to compound individual parenteral nutrition...

Pharmaceutical interventions in parenteral nutrition in a tertiary hospital

BackgroundThe clinical pharmacist's main functions in parenteral nutrition (PN) in the present clinical context are to ensure the quality and safety of the solutions prepared and to verify that the...

Toll-like receptor 4–dependent Kupffer cell activation and liver injury in a novel mouse model of parenteral nutrition and intestinal injury

Infants with intestinal failure who are parenteral nutrition (PN)-dependent may develop cholestatic liver injury and cirrhosis (PN-associated liver injury: PNALI). The pathogenesis of PNALI remains incompletely understood. We hypothesized that intestinal injury with increased intestinal permeability combined with administration of PN promotes lipopolysaccharide (LPS)-Toll-like receptor 4 (TLR4) signaling dependent Kupffer cell (KC) activation as an early event in the pathogenesis of PNALI. We developed a mouse model in which intestinal injury and increased permeability were induced by oral treatment for 4 days with dextran sulphate sodium (DSS) followed by continuous infusion of soy lipid-based PN solution through a central venous catheter for 7 (PN7d/DSS) and 28 (PN28d/DSS) days. Purified KCs were probed for transcription of proinflammatory cytokines. PN7d/DSS mice showed increased intestinal permeability and elevated portal vein LPS levels, evidence of hepatocyte injury and cholestasis (serum aspartate aminotransferase, alanine aminotransferase, bile acids, total bilirubin), and increased KC expression of interleukin-6 (Il6), tumor necrosis factor α (Tnfα), and transforming growth factor β (Tgfβ). Markers of liver injury remained elevated in PN28d/DSS mice associated with lobular inflammation, hepatocyte apoptosis, peliosis, and KC hypertrophy and hyperplasia. PN infusion without DSS pretreatment or DSS pretreatment alone did not result in liver injury or KC activation, even though portal vein LPS levels were elevated. Suppression of the intestinal microbiota with broad spectrum antibiotics or ablation of TLR4 signaling in Tlr4 mutant mice resulted in significantly reduced KC activation and markedly attenuated liver injury in PN7d/DSS mice. These data suggest that intestinal-derived LPS activates KC through TLR4 signaling in early stages of PNALI.

Parenteral Nutrition Therapy Over the Next 5–10 Years

Parenteral nutrition (PN) is one of the most complex medical therapies prescribed by healthcare professionals because it is dependent on the compounding of multiple base solutions to arrive at the final formulation. The delivery of PN is associated with errors in ordering, transcribing, compounding, and delivery of the PN formulations. New compounding technologies will attempt to minimize the potential for these errors. In addition, the associated infectious complications associated with PN therapy need to be minimized. Commercially prepared, premixed, terminally sterilized PN solutions may have an impact. Broader decontamination technologies will be implemented to reduce the incidence of overall nosocomial infections. Modification of PN nutrients, particularly intravenous fat emulsions, will be provided by alternative biological sources, creating fats that may have an improved impact on the patient's immune system and ultimately affecting clinical outcomes.