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Growth of Microorganisms in Total Nutrient Admixtures
Abstract
It has been reported that intravenous fat emulsions, because of their isotonicity and neutral pH, support microbial growth, but traditional parenteral nutrition solutions, being hypertonic and more acidic, are not as supportive. To date, few studies have documented microbial growth in total nutrient admixtures (TNA) containing dextrose, amino acids, fat, electrolytes, vitamins, and trace elements.
This study was undertaken to analyze the growth of Staphylococcus aureus, Candida albicans and four gram-negative enteric bacilli in three different nutrient admixtures, with and without the inclusion of 5% fat emulsion. The composition of the admixtures was either 5, 10, or 25% dextrose; either 0 or 5% fat; and 3% amino acids, electrolytes, vitamins, and trace elements. All admixtures were innoculated with 100 colony-forming units per milliliter, incubated at room (25°C) or refrigerated (4°C) temperature, with samples withdrawn at 0, 3, 6, 12, 24, and 48 hours and plated in triplicate.
Only C. albicans demonstrated any significant growth regardless of fat content. The pH of the admixtures was similar (acidic), and all solutions were hypertonic and found to inhibit bacterial growth.
Conclusions suggest that TNA, when formulated with normal concentrations of additives, is no more likely to support growth of contaminant organisms than the traditional solutions. This contradicts the notion that the addition of fat to total parenteral nutrition will enhance the ability of these admixtures to support microbial growth.
... A total of 24 records [42][43][44][45][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75] ...
... The remaining types of microbe were not amenable to meta-analyses, either because information for each one of them was available from only one study (S. aureus75 , E. cloacae75 , K. pneumoniae75 , K. aerogenes59 and E. durans45 ) and because sample size was only one for each type of infusate (S. marcescens75 ).In each of the meta-analyses grouped by species of microbe(Figures 3.14 to 3.16)the visual variability of the data shown on the forest plots are confirmed by statistical tests of heterogeneity, which are shown in the figures. The first two meta-analyses were based on a glucose concentration of 13.33% w/v, which is equivalent to 1Mcal of glucose (1 gram glucose = 3.75kcal). ...
... The remaining types of microbe were not amenable to meta-analyses, either because information for each one of them was available from only one study (S. aureus75 , E. cloacae75 , K. pneumoniae75 , K. aerogenes59 and E. durans45 ) and because sample size was only one for each type of infusate (S. marcescens75 ).In each of the meta-analyses grouped by species of microbe(Figures 3.14 to 3.16)the visual variability of the data shown on the forest plots are confirmed by statistical tests of heterogeneity, which are shown in the figures. The first two meta-analyses were based on a glucose concentration of 13.33% w/v, which is equivalent to 1Mcal of glucose (1 gram glucose = 3.75kcal). ...
... As the major causes of CRBSI, Staphylococcus aureus, Staphylococcus epidermidis, Serratia marcescens, Escherichia coli, Klebsiella pneumonia, Candida albicans, etc. were shown.1,2,6,7 Furthermore, blood stream infection outbreaks of Bacillus cereus via intravenous line were recently reported in Japan.8 ...
... The results of 3 bacterial species in this study demonstrated that the acidity of the TPN solution is the critical factor suppressing the bacterial growth, but that the hyperosmolality of conventional TPN solutions has a little effect. On the other hand, the results of C. albicans in this study demonstrated that both the acidic pH and the hyperosmolality of TPN solutions hardly have an effect on Candida growth as reported in other studies.6,11,12 ...
... TPN solutions are considered to be relatively good growth mediums for microorganisms due to the components,3,4 whereas a number of investigators have shown that TPN solutions containing hypertonic glucose and amino acids are poor growth media for most nosocomial pathogens, with the exception of Candida and other yeasts.6,9-11 They estimated that the acidic pH and/or the hyperosmolality might suppress the bacterial growth.9,10,12 ...
To identify the microorganisms that can grow rapidly in total parenteral nutrition (TPN) solutions, we investigated the growth of the major causes of catheter-related blood stream infection (Staphylococcus aureus, Serratia marcescens, Bacillus cereus, and Candida albicans) in TPN solutions without lipid.
Experiment 1: A commercial TPN solution without lipid containing multivitamins (pH5.6) was used. A specific number of each test microorganism was added to each 10 mL of the TPN solution and incubated at room temperature. An aliquot of test solution was sampled and inoculated to SCD agar plates at 0, 24, and 48 hrs after the addition of the microorganisms. The number of microorganisms was counted as colony forming units. Experiment 2: The other 2 commercial TPN solutions without lipid (pH5.5) were supplemented with multivitamins. The pH values of the solutions were adjusted to about 6.0, 6.5, or 7.0 using 0.5 mol/L NaOH. The addition of microorganisms, incubation, and counting were performed in the same manner.
Experiment 1: S. aureus, S. marcescens, and B. cereus did not increase in the TPN solution without lipid containing multivitamins (pH5.6), but C. albicans increased rapidly. Experiment 2: The 3 bacterial species did not increase even at pH6.0, but increased at pH6.5 and increased rapidly at pH7.0 in both TPN solutions. C. albicans increased similarly at any pH.
These results suggest that bacterial species cannot grow in TPN solutions without lipid due to the acidity (pH5.6 or lower), but Candida species can grow regardless of the acidity.
... Total nutrient admixture (TNA), single mixture of all the components of PN, has been found to be safe and well tolerated in adults [48,[57][58][59][60]. Perceived advantages of TNA system in adults include shorter time required for daily administration of PN resulting in decrease in nursing time and cost for patient care; and decrease in the risk of formula and vascular access contamination related to reduction of preparation steps, fewer solution containers, decreased violations of the central catheter, avoidance of piggybacking and the inadvertent dislodgement of the additional infusion tubing [55,56,58,61]. ...
... Total nutrient admixture (TNA), single mixture of all the components of PN, has been found to be safe and well tolerated in adults [48,[57][58][59][60]. Perceived advantages of TNA system in adults include shorter time required for daily administration of PN resulting in decrease in nursing time and cost for patient care; and decrease in the risk of formula and vascular access contamination related to reduction of preparation steps, fewer solution containers, decreased violations of the central catheter, avoidance of piggybacking and the inadvertent dislodgement of the additional infusion tubing [55,56,58,61]. However, there is little data regarding its use in neonatal population. ...
Parenteral nutrition (PN) has become an integral part of clinical management of very low birth weight premature neonates. Traditionally different components of PN are prescribed individually considering requirements of an individual neonate (IPN). More recently, standardised PN formulations (SPN) for preterm neonates have been assessed and may have advantages including better provision of nutrients, less prescription and administration errors, decreased risk of infection, and cost savings. The recent introduction of triple-chamber bag that provides total nutrient admixture for neonates may have additional advantage of decreased risk of contamination and ease of administration.
... Total parenteral nutrition (TPN) solutions are considered to be relatively good growth media for microorganisms, 1,4 whereas a number of investigators have shown that TPN solutions are poor growth media for most microorganisms that cause CRBSI, with the exception of Candida species. [5][6][7][8][9] Likewise, we have previously confirmed that while bacterial species do not grow in TPN solutions without lipid, Candida species grow rapidly. 10 Our data have shown that bacterial species cannot grow due to the acidity, but Candida species can grow regardless of the acidity. ...
... 19 As the major causes of CRBSI, Staphylococcus aureus, Staphylococcus epidermidis, Serratia marcescens, Escherichia coli, Klebsiella pneumonia, Candida albicans, etc. were shown. 2,3,6,11 Furthermore, blood stream infection outbreaks of Bacillus cereus via intravenous line were recently reported in Japan. 20 In the present study, we investigated the growth in TPN solutions containing lipid of the same microorganisms studied previously: 10 ie, Staphylococcus aureus as a delegate of gram positive cocci, Serratia marcescens as a delegate of gram negative rods, Bacillus cereus as a delegate of gram positive rods, and Candida albicans as a delegate of fungi. ...
To identify the microorganisms that can grow rapidly in total parenteral nutrition (TPN) solutions, we investigated the growth of the major causes of catheter-related blood stream infection (Staphylococcus aureus, Serratia marcescens, Bacillus cereus, and Candida albicans) in TPN solutions containing lipid.
The pH value of a TPN solution containing lipid (pH 6.0, containing 20 ppm of NaHSO(3)) was adjusted by the addition of HCl to 5.7, 5.4, or 4.9. The pH value of another TPN solution (pH5.5, containing 400 ppm of NaHSO(3)) was adjusted by the addition of NaOH to 5.9, 6.3, or 6.8. A specific number of each microorganism was added to 10 mL of each test solution and incubated at room temperature. The number of microorganisms was counted as colony forming units at 0, 24, and 48 hrs later.
C albicans increased similarly at any pH values in the TPN solution. The bacterial species also increased rapidly at pH6.0 in the solution containing 20 ppm of NaHSO(3), but growth was suppressed as the pH value was reduced, with growth halted at pH4.9. However, these bacterial species did not increase, even at pH5.9, in the other solution containing 400 ppm of NaHSO(3).
These results suggest that Candida species can grow rapidly in almost all TPN solutions regardless of the acidity, lipid, and NaHSO(3); also, some bacterial species may grow in TPN solutions containing lipid unless the pH value is 5.0 or less. Therefore, each TPN solution should be examined whether or not the bacterial species can proliferate.
... This was possibly due to the excessive nutrient density at 5% and 10% concentrations making the solutions hypertonic (Rowe et al. 1987;Havasi et al. 2008;Chen et al. 2020). Whereas, maximum cell density of the order 10 8 CFUs/mL was attained in just 2 weeks after inoculation in 1% concentration of the medium, which also maintained the cell density at 10 5 CFUs/mL for at least 2 months past inoculation. ...
In recent years, the use of probiotic bacteria has attracted the interest of the marine shrimp farming industry. However, there are certain limitations pertaining to the practical application of many commercially available probiotics. Here, a thoroughly screened optimal consortium of three indigenous sulfur probiotics was tested for antibiotic susceptibility and was found to be safe, with each culture being sensitive to all the tested antibiotics. Further, de-potash vinasse (DPV), an environmental hazard, was tested for its prebiotic potential, and its 1% (w/v) concentration was found to be effective for long-term viability (> 66 days) of the probiotic cultures and safe for Artemia. The synbiotic formulation was tested first in a lab-scale microcosm setup successfully and subsequently tried on a shrimp farm; it was observed that the product was congruent to the efficiency of a commercial probiotic regarding almost all physicochemical parameters, sulfide, nitrate–N, nitrite-N, phytoplankton sustenance, Pseudomonas count, coliform count, and heterotrophic count. In addition, it was significantly efficient in maintaining pH, reducing ammonia-N and phosphate-P, Vibrio and Aeromonas count, and a net increase in the yield of shrimp biomass by 625 kg, thus proving to be a better alternative than one of the already available remediation methods.
... Bu sonuçlar diğer araştırmacıların bulgularıyla benzerlik göstermektedir. Yapılan deneysel çalışmaların sonucunda, intravenöz yağlı emülsiyonların mikrobiyal büyümeyi desteklediği ve bakteriyel mikroorganizmaların besleyici lipit ve emülsiyon içeren tüm parenteral solüsyonlarda üreme gösterdiği saptanmıştır [3,19,20,21]. Benzer şekilde, McLeod ve ark. ...
... With regard to microorganisms, Staphylococcus aureus, coagulase-negative staphylococci, Candida albicans, Escherichia coli, Klebsiella pneumonia, etc. have been shown as the major contributors to CRBSIs in patients receiving parenteral nutrition (PN) [2,3,6]. Among these causative microorganisms, only C. albicans can grow in acidic PN solutions [7][8][9][10][11], such as those with a pH of 4.5 [12], and C. albicans causes higher mortality and morbidity than the bacterial species [13][14][15][16][17]. We have previously demonstrated that C. albicans increased slightly in a peripheral parenteral nutrition (PPN) solution consisting of amino acids, carbohydrates and electrolytes, and increased rapidly in the same PPN solution with a lipid emulsion or Ivyspring International Publisher multivitamins (MVs) [18]. ...
Background:
We have previously demonstrated that Candida albicans requires multivitamins (MVs) or lipid to increase rapidly in parenteral nutrition (PN) solutions. In this study, in detail, the effects of vitamins on the growth of C. albicans in PN solutions without lipid were investigated.
Methods:
In the 1st experiment, a commercial PN solution without lipid was supplemented with water-soluble vitamins (SVs: vitamins B1, B2, B6, B12 and C, folic acid, nicotinamide, biotin and panthenol), water-insoluble vitamins (IVs: vitamins A, D, E and K) or both (MVs). In the 2nd experiment, the test solutions were prepared by supplementing the PN solution with one of each or all of the SVs. In the 3rd experiment, another commercial peripheral PN (PPN) solution without lipid was supplemented with SVs, nicotinic acid, biotin or both nicotinic acid and biotin. In each of the experiments, a specified number of C. albicans organisms was added to each test solution, and all of the test solutions were allowed to stand at room temperature (23-26ºC). The number of C. albicans was counted at 0, 24, 48 and 72 hours after the addition of the organism.
Results:
In the 1st experiment, the C. albicans increased rapidly in the PN solution supplemented with the SVs, but increased slowly without the SVs, regardless of the addition of the IVs. In the 2nd experiment, the C. albicans increased rapidly in the PN solution supplemented with the SVs or biotin, but increased slowly with each of the other water-soluble vitamins. In the 3rd experiment, the C. albicans increased rapidly in the PPN solution supplemented with the SVs or biotin, but increased slowly with the addition of nicotinic acid.
Conclusions:
These results suggested that adding MVs or SVs to PN solutions without lipid promotes the growth of C. albicans, and that this effect is mostly attributable to biotin.
... Because of persisting concerns that the addition of an IVFE to PN could make the formulation more hypotonic and less acidic, and thus more hospitable to micro-organisms, 2 quasiin vivo studies were performed. 10,11 Both studies concluded that while an IVFE alone represents a potentially hospitable breeding environment for micro-organisms, the combination of amino acids and dextrose with IVFEs does not. ...
Parenteral nutrition (PN) provides a means of nourishment for patients in whom oral or enteral nutrition is not possible or practical. Initial formulations consisted of carbohydrates (dextrose), amino acids, vitamins, trace minerals, electrolytes, and water. A stable intravenous fat emulsion (IVFE) permitted the combination of all 3 macronutrients in the same admixture (3-in-1 or total nutrient admixture [TNA]). Many institutions have adopted these TNAs as the standard formulation. Others, due to a variety of concerns (including historical concerns regarding stability), continue to administer PN as a formulation of dextrose and amino acids (2-in-1) with separate IVFE infusions. The aim of this article is to review the literature regarding the use of TNA vs 2-in-1 formulations. The published data were critically analyzed, and a preferred strategy was suggested based on an interpretation of the data. Concerns surrounding the safety of 2-in-1 vs 3-in-1 PN formulations can be grouped with respect to those regarding infections, emulsion instability ("cracking"), and precipitant formation. These concerns are largely historical and would seem to be no longer relevant to adult PN formulations. We believe that the available (limited) data support the safe transition to the 3-in-1 formulation as the standard of care in adult PN.
... Some studies suggested that PN is a good medium for microorganisms' growth, 21,22 whereas others have shown that hypertonic glucose and amino acid PN solutions are not good media for most nosocomial pathogens' growth, except for Candida and other yeasts. [23][24][25] In a study from Japan, it was shown that bacterial species cannot grow in PN solutions without lipid due to the acidic environment (pH 5.6 or lower), but Candida species can. 26 Surgical interventions to treat morbid obesity are common and simple and growing in popularity, but they are not without risk of serious complications, including intestinal failure. ...
Obesity is a major chronic disease affecting the U.S. population. Bariatric surgery has consistently shown greater weight loss and improved outcomes compared with conservative therapy. However, complications after bariatric surgery can be catastrophic, resulting in short bowel syndrome with a potential risk of intestinal failure, ultimately resulting in the need for a small bowel transplant. A total of 6 patients became dependent on home parenteral nutrition (HPN) after undergoing bariatric surgery at an outside facility. Four of the 6 patients required evaluation for small bowel transplant; 2 of the 6 patients were successfully managed with parenteral nutrition and did not require further small bowel transplant evaluation. Catheter-related bloodstream infection, a serious complication of HPN, occurred in 3 patients despite extensive patient education on catheter care and use of ethanol lock. Two patients underwent successful small bowel transplantation, 1 died before transplant could be performed, and 1 was listed for a multivisceral transplantation. Surgical procedures to treat morbid obesity are common and growing in popularity but are not without risk of serious complications, including intestinal failure and HPN dependency. Despite methods to prevent complications, failure of HPN may lead to the need for transplant evaluation. In selected cases, the best therapeutic treatment may be a small bowel transplant to resolve irreversible, post-bariatric surgery intestinal failure.
... While lipid emulsion and broth grew all tested organisms (Escherichia coli, Enterobacter cloacae, P. aeruginosa, S. aureus, and C. albicans) in another study, only C. albicans was found to proliferate in TPN [24]. Candida albicans demonstrated significant growth regardless of fat contents (0% or 5%) in admixtures containing variable concentrations of dextrose in an in vitro study [25]. Gram-negative microorganisms such as Klebsiella pneumoniae, E. coli, and P. aeruginosa were able to proliferate in TNA with glucose, amino acids, and lipid emulsion, but growth was impaired in conventional TPN without lipids [26]. ...
Healthcare-associated infections (HAI) in preterm infants are a challenge to the care of these fragile patients. HAI-incidence rates range from 6 to 27 infections per 1000 patient-days. Most nosocomial infections are bloodstream infections and of these, the majority is associated with the use of central venous catheters. Many studies identified parenteral nutrition as an independent risk factor for HAI, catheter-associated bloodstream infection, and clinical sepsis. This fact and various published outbreaks due to contaminated parenteral nutrition preparations highlight the importance of appropriate standards in the preparation and handling of intravenous solutions and parenteral nutrition. Ready-to-use parenteral nutrition formulations may provide additional safety in this context. However, there is concern that such formulations may result in overfeeding and necrotizing enterocolitis. Given the risk for catheter-associated infection, handling with parenteral nutrition should be minimized and the duration shortened. Further research is required about this topic.
... There is conflicting evidence as to whether bacteria grow slowly or not at all in TNA solutions. 27,28 Fungi can still proliferate in admixtures; however, refrigeration at 4°C suppresses all microbial growth. Lipid emulsions alone, on the other hand, do support Gram-positive, Gram-negative, and fungal growth. ...
Proper nutrition and maintenance of a positive energy balance are crucial to an animal’s health. Parenteral nutrition is a medical technique that uses intravenous solutions for nutritional support. Parenteral nutrition has been used to successfully provide nutritional support in ferrets and rabbits for more than a decade at the Massachusetts Society for the Prevention of Cruelty to Animals–Angell Animal Medical Center. The basis for providing nutritional support and the technical expertise is similar to providing proper nutritional support to dogs and cats, with some differences in protein intake depending on whether the patient is a carnivore (ferret) or herbivore (rabbit). This article describes parenteral nutrition and techniques used to provide nutritional therapy for the ferret and rabbit patient.
... when i.v. fat emulsion is used to make total nutrient admixtures (TNAs), it is a poor growth medium 4 and indeed is no worse than 5% dextrose in water. 5 This may be particularly important for neonates and infants receiving nutritional support. ...
Background:
As lipid in parenteral nutrition (PN) purportedly enhances microbial growth, recommendations limit infusion of lipid PN (or lipid emulsion) from a single container to 24h (48h for lipid-free PN). However, the associated evidence base is ambiguous.
Aim:
To examine factors affecting microbial growth in PN.
Methods:
A systematic review with meta-analyses examined effects of nutrients on microbial growth in PN infusates over a 48-h period using the growth ratio {GR=log10[colony-forming units (cfu)/mL at 48h/cfu/mL at time zero]}.
Findings:
Factors influencing GR in PN included glucose, microbial species, temperature, osmolarity, presence of vitamins, trace elements and lipid, and amino acid profile. Using unmatched datasets (N=306), a general linear model found that lipid inclusion in PN represented 3.3% of the variability, which was less than that due to glucose concentration (5.8%), microbial species (35.3%) and microbe-infusate interaction (4.4%). Using matched datasets (N=38 pairs), lipid inclusion in PN represented 5.4% of the variability (P=0.076), which was less than that due to glucose concentration (8.5%; P=0.025), microbial species (75.5%; P<0.001) and microbe-infusate interaction (13.3%; P=0.382). Using meta-analyses of matched datasets, the presence of lipid in PN at fixed glucose concentrations did not significantly increase GR of Candida albicans, Escherichia coli or Staphylococcus epidermidis (P=0.352, P=0.025 and P=0.494, respectively; overall P=0.175).
Conclusion:
Lipid inclusion in PN is only one of several factors that may influence microbial growth in PN. Any recommendations about the duration of PN infusion from a single container should account for all these factors, and should be weighted according to microbial species likely to contaminate PN.
Parenteral nutrition (PN) is a life-sustaining therapy providing nutrients to individuals with impaired intestinal tract function and enteral access challenges. It is one of the most complex prescriptions written routinely in the hospital and home care settings. This article is to aid the nutrition support clinician in the safe provision of PN, including selecting appropriate patients for PN, vascular access, development of a PN admixture, appropriate therapy monitoring, recognition of preparation options, and awareness of preparation and stability concerns.
Medicinal Gases Volatile Anesthetics Concluding Remarks References
Background: Recommendations effectively restrict the infusion duration of lipid-containing parenteral nutrition (PN) from a single bag, purportedly because it encourages growth of potential microbial contaminants more than lipid-free PN. Since other variables, including osmolarity, may independently affect microbial growth, this study examined variables affecting growth of Escherichia coli and Enterococcus durans in PN infusates. Materials and Methods: Growth of E coli and E durans was assessed in quadruplicate in 12 different PN infusates, with and without lipid, in varying glucose concentrations. Results: Results are presented as mean log10 colony-forming units (cfu)/mL ± SEM at 48 hours. The log10cfu/mL of both E coli and E durans in PN increased considerably after adjustment for baseline log10cfu/mL and pH, from 1.093 to 2.241 (P < .001) and from 0.843 to 3.451 (P < .001) respectively. Growth of each microorganism was independently increased by lipid inclusion, or increasing the proportion of nonnitrogen energy from lipid, and reduced by raising the glucose concentration or energy density. Increasing the osmolarity of lipid-PN with glucose or sodium chloride reduced growth but only significantly for sodium chloride (E coli, P = .025; E durans, P = .045). Induced changes in pH affected the growth of the 2 organisms differently. Conclusion: The presence of lipid and an increasing proportion of energy from lipid in PN favored the growth of E coli and E durans. Osmolarity changes and the nutrient type causing these changes independently affect the growth of these microbes. Each effect needs to be considered when establishing guidelines based on the growth of potential contaminants in different types of PN.
The decision to initiate total parenteral nutrition (TPN) in hospitalised patients should be based on the presence of clinically significant starvation and dysfunction of the gastrointestinal tract. It must also take into account the clinical status of the patient, considering major treatment strategies and the need for prolonged hospitalisation, the benefits of feeding and the attendant risks of central venous alimentation. Recent evidence in surgical patients in intensive care provides the impetus for early parenteral feeding; withholding TPN and inducing a cumulative caloric deficit of ⩾10 000 calories has been associated with a survival disadvantage compared to those patients with a positive caloric balance. Moreover, the incidence of serious organ failure was consistently higher in the group with cumulative caloric deficits. Additional evidence favouring the provision of TPN exists, but the axiom ‘if the gut works, use it’ still prevails. Exceptions to this precept do exist, however, particularly in critically ill patients. The metabolic derangements encountered in these patients could be so severe that it may be impossible to correct the electrolyte and acid-base abnormalities via the enterai route. For example, such patients may have large potassium requirements and/or severe alkalaemia necessitating systemic acidification with hydrochloric acid, precluding enterai delivery due to gastrointestinal intolerance. In this setting, combined enterai feeding with 10 to 20 ml/h to maintain gut integrity (via a post-pyloric feeding tube) and TPN during the acute phases of illness is an exciting possibility.
Once the decision to feed is made, the amount of nutrition prescribed may assume equal importance with respect to patient outcome. The frequent use of the Harris-Benedict equation, plus a multiplying factor for stress, may overestimate caloric requirements; this is particularly true during critical illness. The dangers of overfeeding may be just as harmful as not feeding at all. The use of indirect calorimetry provides the most accurate measurement of resting energy expenditure. However, in the absence of indirect calorimetry, modified equations to estimate caloric needs are available. Caution must be observed as caloric intakes exceeding the range of 25 to 35 kcal/kg may be dangerous, particularly in the severely ill patient with preexisting organ failure.
The amount of protein and the ‘calorie-mix’ necessary for optimal nutritional support is open to debate. Recent evidence has demonstrated no additional benefit to nitrogen balance in severely septic patients when protein was given at a level exceeding 1.5 g/kg/ day. Similarly, protein intakes >1.75 g/kg/day in patients with advanced gastrointestinal cancer did not achieve a state of net protein synthesis. Therefore, for most patients with moderate to severe degrees of stress, a level of protein intake up to 1.75 g/kg/day is reasonable, since levels above this offer no additional benefits and most likely lead to ureagenesis.
Carbohydrate intake is important for a number of vital physiological functions, and it is an essential macronutrient. However, excessive glucose administration is associated with a number of adverse effects. In general, glucose infusion rates should not exceed 4 mg/kg/min for 2 reasons: first, this rate is equal to its optimal infusion rate, and dosages above this level increase the rate of lipogenesis; and second, even doubling its optimal infusion rate has not been shown to improve protein-sparing in severely stressed patients. Hence, the carbohydrate content should generally not exceed 4 mg/kg/min (i.e. approximately 400g in the reference 70kg man) with the balance of the calories provided as lipids. When given as long chain triglycerides (LCT), lipids should preferably be given continuously as a 3-in-l or total nutrient admixture.
Finally, we recommend that nutrition support teams take an aggressive approach to the management of severely ill patients. Manipulations that reduce volume burdens, such as concentrating all separate (i.e. piggyback) infusions, as well as using the TPN as a drug vehicle (where appropriate), will afford greater likelihood of providing the necessary protein and calories. Furthermore, managing the plethora of metabolic derangements, frequently encountered in the intensive care unit (i.e. acid-base and electrolyte disturbances) via the TPN should reduce the dangers of protracted imbalances. It is obvious that professional training of pharmacists and physicians specialising in clinical nutrition is needed to achieve optimal care of these patients.
Microbial contamination associated with different methods of neonatal intravenous fat emulsion (IVFE) preparation and delivery was evaluated.
Sterility testing was performed on IVFE dispensed via three different methods: (1) in the original container (n = 60), (2) repackaged into a syringe (n = 90), and (3) drawdown of the original container (n = 60). At the end of each infusion (24 hours for methods 1 and 3, 12 hours for method 2), a sample of the IVFE was withdrawn from the container using a sterile syringe in an International Organization for Standardization class 5 hood and sent to the hospital microbiology laboratory, where the samples were introduced into blood culture bottles and incubated for five days. Each sample was then subcultured on a blood agar plate with olive oil and left for an additional two days in a carbon dioxide incubator to assess for Malassezia furfur.
None of the samples from the original containers showed bacterial or fungal growth. Three of the samples from syringes had bacterial growth (two samples contained coagulase-negative staphylococcus and one contained both Klebsiella oxytoca and Citrobacter freundii), yielding a contamination rate of 3.3%. The number of contaminated samples did not significantly differ among the three preparation methods (p = 0.13).
Repackaging IVFE into sterile syringes resulted in bacterial contamination and should be avoided in clinical practice. IVFE samples obtained using the drawdown procedure under sterile conditions for infusion over 24 hours revealed no microbial contamination.
The use of intravenous fat emulsions has become an integral part of the provision of parenteral nutrition. In the past, this was achieved by the administration of lipids separately from the dextrose-amino acid base solution. More recently, lipids have been admixed along with the dextrose-amino acid formula as a total nutrient admixture (TNA). This article discusses the advantages and disadvantages of TNAs, the factors that affect the stability of emulsions, the potential for microbial growth in TNAs, and guidelines for the compounding of TNAs.
Emulsion stability of total nutrient admixtures containing TrophAmine amino acid injection admixed with Intralipid, Nutrilipid, and Liposyn II was studied. High and low electrolyte concentrations were added to each total nutrient admixture before storage at 4 degrees C for 48 hours then at 20-22 degrees C for 24 hours. Stability studies were also performed on total nutrient admixtures containing higher concentrations of fat emulsion and total nutrient admixtures with added cysteine hydrochloride and carnitine. High electrolyte concentrations only were added to these total nutrient admixtures before being stored refrigerated for 24 hours then at room temperature for 24 hours. Visual assessment, pH determination, and particle size analysis were performed immediately after compounding and after refrigerated and room temperature storage. Particle size was assessed by measuring the mean diameter of the fat emulsion and the percent of oil volume in particles greater than 5 microns. Repeated-measures analyses of variance were used to determine significance of type or concentration of fat emulsion, electrolyte concentrations, or time on mean diameter or percent particles greater than 5 microns. There were minimal changes in pH values over time. Creaming was observed in all total nutrient admixtures at all sampling times except time zero. This was reversible upon agitation. Results of particle size analysis over time indicated little change in mean diameter or percent particles greater than 5 microns. These minimal changes did not seem to be clinically significant. It is concluded that total nutrient admixtures prepared with this pediatric amino acid formulation are stable when prepared and stored as reported.
Disseminated candidiasis is frequently unrecognized because of a lack of clinical signs. However, pneumonia and osteomyelitis are frequently presenting features of systemic candidiasis, and its early detection is crucial to successful management. The widespread use of broad-spectrum antibiotics, corticosteroids, chemotherapeutic drugs, and radiation therapy, particularly in debilitated patients, has led to the emergence of infections by fungi formerly believed to be nonpathogenic in man. Patients with head and neck cancer are at increased risk for developing opportunistic infections because they are immunologically compromised.We describe a patient with carcinoma of the floor of the mouth who developed disseminated candidiasis that was followed by pneumonia and lumbar vertebral osteomyelitis after radiation treatment and surgery.
The introduction of total nutrient admixtures (TNAs) has offered several clinical advantages. Substituting a portion of the daily dextrose calories with lipids may reduce the incidence of carbohydrate-associated complications (e.g., disturbances in glucose control and immune function). In addition, providing intravenous lipids continuously over 24 hours as a TNA appears to be better utilized by the liver and less likely to interfere with reticuloendothelial system function when compared with conventionally administered, discontinuous lipid infusions. If the peripheral vein is used as a route for parenteral nutrition, the addition of fat to the admixture provides the advantage of enhancing caloric density, while contributing significantly less tonicity than dextrose. Certain pharmaceutical and microbiological issues need to be considered to ensure the intravenous administration of a safe and homogenous dispersion. Attention to established guidelines provided by the lipid manufacturers, as well as careful extrapolation of TNA stability data, will avert the dangers associated with infusion of coalesced lipid particles. This article reviews the evidence supporting the use of lipids as daily caloric sources, with particular emphasis on the role of the total nutrient admixtures as the primary vehicle for administration.
Previous study demonstrated that patients who received total parenteral nutrition (TPN) with standard intermittent infusion of long chain triglyceride (LCT) at 0.13 g kg-1hr-1 over 10 hr for each of three days showed a significant decline in 99Tc-sulfur colloid (TSC) clearance rate by the reticuloendothelial system (RES). The present studies evaluated eight patients who received the same total lipid dose of LCT infused continuously as in a three-in-one admixture, and another nine patients receiving the same amount of fat as a medium chain triglyceride (MCT)/LCT (75%/25%) emulsion intermittently over 10 hr at 0.13 g kg-1hr-1 for three consecutive days. Patients were given continuous total parenteral nutrition (TPN) comprised of protein, 1.5 g kg-1day-1, and dextrose, 4.5 g kg-1day-1. RES function was examined by measuring the clearance rates of intravenously injected TSC while receiving TPN containing only protein and dextrose, and again after three days of fat infusion. Mean (+/- SEM) clearance rate constants before and after continuous LCT infusion were 0.38 +/- 0.09 and 0.41 +/- 0.08 min-1, respectively, while those before and after intermittent MCT/LCT infusion were 0.50 +/- 0.18 and 0.73 +/- 0.24 min-1, respectively. In contrast to intermittent LCT infusion, the administration of continuous LCT or an intermittent MCT/LCT mixture does not impair TSC clearance by the RES. These findings suggest that condensing the daily period of LCT infusion at standard dosage may exceed the rate of metabolic utilization, resulting in increased fat removal and diminished TSC uptake by the RES.(ABSTRACT TRUNCATED AT 250 WORDS)
The decision to initiate total parenteral nutrition (TPN) in hospitalised patients should be based on the presence of clinically significant starvation and dysfunction of the gastrointestinal tract. It must also take into account the clinical status of the patient, considering major treatment strategies and the need for prolonged hospitalisation, the benefits of feeding and the attendant risks of central venous alimentation. Recent evidence in surgical patients in intensive care provides the impetus for early parenteral feeding; withholding TPN and inducing a cumulative caloric deficit of greater than or equal to 10,000 calories has been associated with a survival disadvantage compared to those patients with a positive caloric balance. Moreover, the incidence of serious organ failure was consistently higher in the group with cumulative caloric deficits. Additional evidence favouring the provision of TPN exists, but the axiom 'if the gut works, use it' still prevails. Exceptions to this precept do exist, however, particularly in critically ill patients. The metabolic derangements encountered in these patients could be so severe that it may be impossible to correct the electrolyte and acid-base abnormalities via the enteral route. For example, such patients may have large potassium requirements and/or severe alkalaemia necessitating systemic acidification with hydrochloric acid, precluding enteral delivery due to gastrointestinal intolerance. In this setting, combined enteral feeding with 10 to 20 ml/h to maintain gut integrity (via a post-pyloric feeding tube) and TPN during the acute phases of illness is an exciting possibility. Once the decision to feed is made, the amount of nutrition prescribed may assume equal importance with respect to patient outcome. The frequent use of the Harris-Benedict equation, plus a multiplying factor for stress, may overestimate caloric requirements; this is particularly true during critical illness. The dangers of overfeeding may be just as harmful as not feeding at all. The use of indirect calorimetry provides the most accurate measurement of resting energy expenditure. However, in the absence of indirect calorimetry, modified equations to estimate caloric needs are available. Caution must be observed as caloric intakes exceeding the range of 25 to 35 kcal/kg may be dangerous, particularly in the severely ill patient with preexisting organ failure. The amount of protein and the 'calorie-mix' necessary for optimal nutritional support is open to debate. Recent evidence has demonstrated no additional benefit to nitrogen balance in severely septic patients when protein was given at a level exceeding 1.5 g/kg/day.(ABSTRACT TRUNCATED AT 400 WORDS)
Pre-mixed amino acid and dextrose solutions used for parenteral nutrition had additions made to them at a ward level by medical officers. Samples of the solutions of the study group and a control group were taken at six hours and at the end of the infusion time and were analysed microbiologically for growth of microorganisms. No organism was isolated from either group. We conclude that making additions to pre-mixed amino acid/dextrose solutions at the ward level does not constitute a microbiological hazard for the patient.
The response to major trauma is characterized by a significant erosion of the body cell mass. Intensive nutritional support can decrease morbidity and mortality. Preservation and restoration of the body cell mass involves amino acid synthesis into protein, and this process requires nutrient energy. Newer methods of assessing energy expenditure have revised traditional concepts about energy requirements following trauma. The use of fat to meet some of the caloric requirements may obviate problems with ventilatory distress, glucose intolerance, and hepatic steatosis that occur with glucose-based nutritional regimens. Selection of the delivery method for intensive nutritional support should consider gastrointestinal integrity, physiologic tolerance, and cost. Enteral nutrition is superior to parenteral nutrition in maintaining gastrointestinal mucosal integrity, hormonal balance, and nutrient utilization. Furthermore, it is safer, more convenient, and more economical than parenteral nutrition.
The survival of beta-lactamase-producing (beta-lac+) and non-beta-lactamase-producing (beta-lac-) Bacillus and Staphylococcus spp. has been investigated in dextrose 5% injection, NaCl 0.9%, and dextrose 5% in NaCl 0.9% solutions. Tests were performed under static and turbulent conditions of incubation, with and without antibiotics added to the fluids, and with or without 1% citrated blood. All solutions were inoculated with about 1000 organisms/mL, and sampled for viable bacteria at specific time intervals. Under static conditions, there was no significant decrease in viability (p greater than 0.01) of the bacilli, except for the staphylococci (p less than 0.01). However, when cultures were agitated, all species showed significant decline in viability (p less than 0.01). When antibiotics were present, S. aureus (beta-lac+) declined gradually throughout 24 hours (p greater than 0.01). B. cereus (beta-lac+) concentrations were static in all solutions. All organisms multiplied rapidly in solutions containing blood. The results suggest that the growth characteristics of both beta-lac+ and beta-lac- bacteria in intravenous fluids are essentially similar, except in solutions containing beta-lactamase-sensitive antibiotics in which beta-lac+ bacteria tend to survive.
Since its inception, the field of parenteral nutrition has continued to evolve requiring the expertise of several health care disciplines. This feature has made nutrition support unique among clinical subspecialties. As a member of this team, the pharmacist plays a critical role in the provision of sterile admixtures, compatible nutritional formulations, and cost-effective, therapeutically equivalent strategies. The pharmacist has become more involved in the clinical care of the patient, with particular emphasis on the development of drug-induced metabolic disorders. The multitude of drugs prescribed to hospitalized patients increases the potential for serious metabolic disturbances. This is especially true in the critical care setting where sudden changes in metabolism (e.g., acid-base homeostasis, fluid and electrolyte balance) may result in profoundly negative effects. The critical care setting also represents the most sensitive period of hospitalization where even subtle changes in metabolic homeostasis may assume major clinical significance. Early recognition of offending agents and the institution of appropriate intervention may avert serious iatrogenic diseases. The nutrition support team is in a unique position to address many such disorders through selective manipulation of the various components in the parenteral nutrient admixture. The ability of the pharmacist to recognize the development of drug-induced metabolic disorders lends further support for clinical pharmacy in nutrition support services.
The extraordinary growth properties of most microorganisms in 10% and 20% lipid emulsions has led to the Centers for Disease Control and Prevention recommendation that if lipids are given through an i.v. line, the administration set should be replaced every 24 hours rather than the usual 72-hour interval used for crystalloid solutions, including those used for conventional total parenteral nutrition. For nearly 15 years, parenteral alimentation has been given as a total nutrient admixture (TNA), with the glucose, amino acids, and lipid mixed within the same bag and infused continuously over 24 hours.
We prospectively studied in a representative TNA (17.6% glucose, 5% amino acids, 4% lipid; pH 5.6, osmolality 1778) and in a control solution, 5% dextrose-in-water (D5%/W), the growth properties at 4, 25, and 35 degrees C of three isolates each of Staphylococcus epidermidis, Staphylococcus aureus, Enterobacter cloacae, Klebsiella oxytoca, Serratia marcescens, Acinetobacter calcoaceticus, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, Burkholderia cepacia, Flavobacterium spp, and Candida albicans, and two isolates of Staphylococcus saprophyticus, the species that are most likely to contaminate TNA during preparation or administration and that have been implicated in >95% of all outbreaks and sporadic cases of nosocomial bloodstream infections traced to contaminated parenteral admixtures reported in the world literature.
Growth in TNA at 25 and 35 degrees C occurred with only two species, C. albicans and S. saprophyticus, and only after 24 to 48 hours; D5%/W allowed growth at 25 degrees C of two gram-negative species, S. marcescens and B. cepacia.
We conclude that TNA is a poor growth medium for most nosocomial pathogens and is no better than D5%/W. The need to replace administration sets every 24 hours with TNA should be reconsidered and ideally be studied in a prospective randomized trial.
Malnutrition in the form of insufficient nutrient intake to support tissue metabolism undermines appropriate medical or surgical therapeutic management of a case. The major consequences of malnutrition in all patients are decreased immunocompetence, decreased tissue synthesis and repair, and altered intermediary drug metabolism. A practical goal is to begin nutritional support within 24 hours of the injury, illness, or presentation. There are only two methods by which nutrients can be supplied to the body: enteral and parenteral. General guidelines are presented to help establish a foundation.
The most serious complication of prolonged intravenous infusion of hypertonic dextrose and amino acids is infection. Frequently, the etiology is fungal rather than bacterial. Previous authors have suggested that bacterial survival and growth in the solutions is suppressed by (a) high dextrose concentration, (b) high osmolality, or (c) low pH. This paper presents evidence that proposals (a) and (b) are untenable and (c) is only partly responsible. We call attention to the presence of a factor that is antibacterial but not antifungal; namely, a high concentration of glycine.
Total nutrient admixtures (TNAs) containing dextrose, amino acids, and fat emulsion were evaluated for their ability to support bacterial and fungal growth. The following solutions were tested: a standard adult total parenteral nutrient (TPN) solution with dextrose, amino acids, and electrolytes, a standard neonatal TPN solution with dextrose, amino acids, and electrolytes, a 10% fat emulsion, a 20% fat emulsion, a TNA with 40% of the total calories as fat, a TNA with 25% of the total calories as fat, a neonatal TNA with 25% of the total calories as fat, a control (fat emulsion was replaced with an equal amount of sterile water) for solution 5, and a control for solution 6. Serial dilutions of each solution were inoculated with 5 X 10(5) bacteria/mL or 5 X 10(3) fungi/mL, incubated, and visually rated on a scale of 0 (no growth) to 4 (maximal growth). Bacterial growth of Pseudomonas aeruginosa, Staphylococcus aureus, Staph. epidermidis, Streptococcus faecalis, and Group JK Corynebacterium was greater in the TNA solutions than in the control or standard TPN solutions. Escherichia coli, Candida tropicalis, and C. albicans grew in all solutions tested. Torulopsis glabrata grew better in solutions that did not contain fat emulsion. Growth characteristics did not differ significantly between the adult and neonatal (more dilute) solutions. The addition of fat emulsion to TPN solutions enhances the ability of these solutions to support bacterial growth; this possibility must be considered when evaluating patients for this type of total parenteral nutrition therapy.
A number of parenteral fluids were assessed as substrates for bacterial and yeast growth. No microorganism underwent significant growth in any solution during the first 24 hours of incubation at room temperature with the exception of Candida albicans, which proliferated in a casein hydrolysate TPN solution. A crystalline amino acid TPN solution is a poor growth medium for microorganisms as compared to the casein hydrolysate solution. Suggestions are made relative to the preparation and proper use of TPN solutions in adult and pediatric hyperalimentation.
• Parenteral nutrition via central venous catheterization is associated with serious risks, especially that of sepsis. Lipid emulsion (Intralipid [Sweden]), which may be administered peripherally, was evaluated for its potential to support microbial growth. Washed cultures of Staphylococcus aureus, Candida albicans, and three species of Gram-negative rods were all capable of multiplying in the emulsion at room temperature. Variations in inoculum size did not affect the growth rate. Studies comparing the emulsion to amino acid-glucose solutions (total parenteral nutrition [TPN]) confirmed other reports that TPN inhibits the growth of certain bacteria but merely retards fungal multiplication. When human serum was added to the lipid emulsion in an attempt to simulate in vivo conditions at the catheter tip, Escherichia coli was inhibited while the growth of S aureus and C albicans was unaltered.
(Arch Surg 110:1479-1481, 1975).
Parenteral nutrition via central venous catheterization is associated with serious risks, especially that of sepsis. Lipid emulsion (Intralipid[Sweden]), which may be administered peripherally, was evaluated for its potential to support microbial growth. Washed cultures of Staphylococcus aureus, Candida albicans, and three species of Gram-negative rods were all capable of multiplying in the emulsion at room temperature. Variations in inoculum size did not affect the growth rate. Studies comparing the emulsion to amino acid-glucose solutions (total parenteral nutrition [TPN])confirmed other reports that TPN inhibits the growth of certain bacteria but merely retards fungal multiplication. When human serum was added to the lipid emulsion in an attempt to simulate in vivo conditions at the catheter tip, Escherichia coli was inhibited while the growth of S aureus and C albicians was unaltered.
Cells of the pathogenic yeast Candida albicans accumulate as unbudded singlets at stationary phase in defined medium at 25 °C. When released into fresh medium at 37 °C and pH 6.5, these cells will synchronously form elongate pseudomycelia, and when released into fresh medium at either 25 °C, pH 6.5, or 37 °C, pH 4.5, they will synchronously form buds. Using pH and temperature shift experiments, we have examined when cells become committed to pseudomycelium formation and bud formation under conditions conducive to each growth form respectively. It is demonstrated that in either case commitment occurs long after release from stationary phase, at approximately the same time the first evagination is visible on the cell's surface. In addition, it is demonstrated that once a released cell has formed a bud, it and its progeny lose the capacity to form pseudomycelia until they re-enter stationary phase; on the other hand, elongating pseudomycelia retain the capacity to form buds. The possible relationships of the commitment events to septation and to the cell cycle are discussed.
Appropriately mixed, compatible solutions of glucose, amino acids and lipid have recently become available for clinical use. While a single hyperalimentation solution has several advantages over the conventional two-bottle technique, its effect on infusion-related septicemia is unknown. An in vitro, mock infusion system identical to that used in our new-born intensive care unit was set up to assess the relative growth rates of three microorganisms in several parenteral nutrition mixtures. Growth of Staphylococcus epidermidis, Escherichia coli and Candida albicans was measured in seven different alimentation solutions, including two combined solutions. Generally, microbial growth was the same or decreased in combined solutions as compared to fat alone although considerably greater than that observed in nonlipid containing solutions. In addition, the ability of these organisms to pass in-line terminal filters of pore size 0.22 and 1.2 microns was assessed.
Microbial growth of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans was evaluated in a standard amino acid‐dextrose‐based total parenteral nutrition (TPN) solution, 10% lipid emulsion, and a combined TPN formulation containing amino acids, dextrose, and lipid emulsion. At an initial inoculum of 10 ⁴ CFU/ml, all three bacterial organisms grew well in 10% lipid emulsion, died in the standard solution and grew only minimally or died in the combined formulation. C. albicans grew in all three formulations at an initial inoculum of 10 ⁴ CFU/ml; however, at an initial inoculum of 10 ² CFU/ml, which approximates touch contamination, growth of Candida in the standard and combined formulations was <1 log at 24 hr in contrast to the 10% lipid emulsion which showed significant growth >2 log at 24 hr.
It is concluded that a 24‐hr infusion time is safe for the combined TPN formulation used in this study. This should result in significant cost savings compared to the previously recommended 12‐hr infusion time. ( Journal of Parenteral and Enteral Nutrition 10: 494–497, 1986)
The effect of lipid addition to TPN (Total Parenteral Nutrition) solutions on microbial growth was investigated. Staphylococcus epidermidis, which failed to grow or grew poorly in the absence of lipid, reached greater than 10(4) cfu/ml (colony forming units per ml), from an initial inoculum of approximately 50 cfu/ml after 24 h when lipid was added. Candida albicans grew more slowly in the presence of lipid, but nevertheless reached 10(4) cfu/ml after 40 h incubation. Klebsiella aerogenes grew readily in all solutions, whereas Escherichia coli failed to grow in any solution. Growth of S. epidermidis and K. aerogenes was improved when the inoculum consisted of starved cells; however, growth of starved cells of C. albicans lagged behind that of unstarved cells. The ability of S. epidermidis to grow in lipid-containing TPN mixtures is particularly important, since this organism is frequently associated with sepsis. In an infant surgical unit, where TPN is under the care of a nutrition team, samples of TPN fluids and giving sets were examined for microbiological contamination at the end of the 24 h administration period. Contamination was found in eight of the 98 systems examined from eight patients. The organisms were identified as coagulase-negative staphylococci and diphtheroids.
C albicans, T glabrata, and certain bacterial pathogens proliferate rapidly at room temperature in TPN solution prepared from casein hydrolysate and dextrose. Fungi grow more slowly in TPN solution prepared from synthetic amino acids and dextrose, and the bacteria tested fail to multiply, apparently because of a lack of growth factors and an inhibitory phenomenon. Therefore, the use of synthetic amino acid-dextrose solution may decrease the risk of sepsis if contaminated fluid is infused. TPN fluid should be used as soon as possible after preparation, but if solutions must be stored, refrigeration at 4°C will suppress growth of the pathogens tested.
A major problem in total parenteral nutrition is sepsis, particularly that caused by Candida. Studies of four solutions, a casein hydrolysate, a fibrin hydrolysate, and two crystalline amino acid solutions, show that the protein hydrolysate solutions appear to be highly selective for Candida over bacteria, whereas the crystalline amino acid solutions are not. These findings suggest that the crystalline amino acid preparations may offer a partial solution to the infection problem by minimizing the contribution of the solution as a reservoir for organism multiplication, because they retard the growth of both bacteria and Candida.
The ability of Candida albicans (American type culture collection 10231) a known human pathogen, to grow in various amino acid and dextrose mixtures available for human parenteral nutrition was investigated in vitro by colony counts, generation times, and growth curve analysis. Growth of this pathogen occurred rapidly in all mixtures at 30 and 37 C, was inhibited by cooling to 4 C. Growth was greater in solutions containing amino acids, dextrose, and electrolytes than it was in dextrose, or amino acids, or amino acid with electrolytes alone. Growth varied to the quantity of the constituent amino acids. Thus cooling should be an essential feature of storage and the actual content of these mixtures should be a consideration before embarking on therapy.
The study reports on the frequency of contamination of hyperalimentation and commonly used intravenous solutions during their preparation in the pharmacy and utilization in the hospital ward area. A total of 321 intravenous infusion samples, including 85 samples of hyperalimentation solution, were collected from the patient's bedside and were cultured in thioglycoUate broth. The commonly used intravenous solutions demonstrated a low rate of bacterial contamination of 3.8%. In contrast, contamination of "in use" hyperalimentation fluids by Candida species occurred frequently (>25%). Storage of freshly prepared hyperalimentation solutions under various conditions did not result in either bacterial or fungal contamination. The study shows that the risk of contaminating intravenous solutions,, including hyperalimentation solution, duing preparation in 3ie pharmacy is low providing vigorous aseptic techniques are practiced. In vitro studies in which hyperalimentation solutions were seeded with various organisms including fungi showed that, although it was an excellent medium for maintaining the growth of fungi, bacterial survival: and growth were more difficult to demonstrate.
The ability of parenteral lipid emulsions to support microbial growth was compared using commercially available brands of lipid emulsion. Both 10 and 20% concentrations of soybean and safflower oil emulsions were used. Washed cultures of six gram-negative, three gram-positive, and one yeast, in concentrations of 1 x 10(4) to 2 x 10(4) colony-forming units/ml, were inoculated into lipid emulsion aliquots and stored at room temperature. There were than subcultured at 0, 6, 12, 24 and 48 hr. After 48 hr at 37 degrees C, growth was recorded as colony-forming units/ml. Normalized growth curves were expressed as mean +/- SEM. ANOVA demonstrated no difference in growth patterns due to the nature of the oil or its concentration. Gram-negative organisms multiplied faster when compared to gram-positive (p less than 0.05 at 12 hr, p less than 0.01 at 24 hr, and p less than 0.005 at 48 hr). Yeast grew as well as bacteria. The Center for Disease Control's recommendation of a 12-hr hang time for parenteral lipid emulsions should be observed until correlation of laboratory microbial growth patterns and clinical use are studied further.
Microbial growth patterns were studied in intravenous fat emulsions under conditions that simulated touch contamination before or during administration. Commercially available emulsions of 10% and 20% soybean oil and 10% safflower oil in 500-ml bottles were inoculated with two concentrations of each of four organisms: a coagulase-negative Staphylococcus isolated from a venipuncture site, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans. The bottles were kept at room temperature, and samples were taken by direct puncture of the i.v. port at 0, 3, 6, 12, 24, 48, and 72 hours, diluted, and plated. Emulsions were visually inspected daily. Growth of the coagulase-negative Staphylococcus was minimal for 48 hours. E. coli showed substantial growth within 12 hours in all three emulsions. Growth patterns for Ps. aeruginosa were similar in all emulsions, and growth approximated that of E. coli within 48 hours. The growth rate of C. albicans was intermediate between that of Staphylococcus and those of E. coli and Ps. aeruginosa. Growth of C. albicans was greater in 10% safflower oil emulsion than in the other emulsions. No physical changes were observed. The coagulase-negative Staphylococcus showed less growth than C. albicans, Ps. aeruginosa, and E. coli. Substantial growth within 12 hours was seen only with E. coli. C. albicans exhibited preferential growth in 10% safflower oil emulsion.
The yeast-mycelial transition in Candida albicans can be induced from yeast cells grown on minimal defined medium only in stationary phase. This study examined the inducibility of cultures in which growth was limited by the availability of the nutrients, glucose, NH4Cl, or galactose. The results showed that neither stationary phase nor cell cycle stage alone was a sufficient condition to support subsequent germ tube formation. In addition, final cell concentration alone was not a factor in inducibility. When a hundredfold decrease in growth was obtained by limiting any of the nutrients, a loss in inducibility was observed. However, the loss of inducibility differed with the limiting nutrient. Galactose, NH4Cl, and glucose-limited cultures showed respectively 15, 30, and 80% loss of inducibility. Thus the effect was associated with both carbon/energy and nitrogen-limited cells; however, glucose appeared to have a specific effect. These observations suggest that the metabolic state of the stationary phase yeast cell was an important factor in the subsequent ability to respond to conditions inducing germ tube formation.
Stationary phase yeast cells of the dimorphic fungus albicans can reinitiate growth under appropriate conditions either as yeasts through bud formation or as hyphae through germ tube formation and elongation. Stationary phase yeast cells resuspended in fresh medium at 37 degrees C form germ tubes and those resuspended at 25 degrees C form buds. Temperature shift experiments have been used to observe when cells become committed to germ tube formation and yeast budding growth under conditions favorable to each form. The two commitment processes appear to be independent and, once initiated, occur at characteristic rates with commitment to germ tube formation preceding commitment to yeast bud formation. The rate of commitment to germ tube formation was consistent with a random process or first-order kinetics. A relationship between cell volume and commitment to yeast growth and bud emergence was consistent with observations of cell volume distribution both in stationary phase cultures and between budded and unbudded cells during resumption of growth at 25 degrees C.
Changes in the identity and quantity of proteins synthesized during morphogenesis may result from alterations in gene expression in the dimorphic yeast Candida albicans. Stationary phase yeast cells, upon resuming growth at 25 degrees C, form budding yeast and at 37 degrees C form germ tubes. In order to identify proteins associated with morphogenesis, we compared cytoplasmic proteins synthesized during germ tube and bud formation. Proteins synthesized during this period were labeled at four intervals with either [3H]leucine or [35S]methionine and separated by two-dimensional polyacrylamide gel electrophoresis. This study shows that, of the 230 proteins resolved on each gel, 5 were specific to the yeast morphology and 2 proteins showed reduction in net synthesis in the mycelial phase. There were, however, no mycelium-specific proteins at any labeling period. The majority of proteins were common to both morphologies and showed no major shift in number during resumption of growth. The observations reported here suggest that differential gene expression occurs during morphogenesis of C. albicans.
Although adherence to aseptic techniques for cathether insertion and limiting the duration of cannulation to less than 3 days will prevent the majority of infusion-related infections, some will continue to occur. The clinical outcome of these infections depends upon early recognition with prompt initiation of appropriate therapy. Therefore, the following guidelines are presented as an aid to the management of suspected infusion-related infections: Discontinue the entire infusion including the delivery apparatus. Carefully examine the cannulation site (and any previous sites) for any signs of inflammation. Immediately after the catheter is removed, the vein should be milked for pus. A Culturette (Marion Scientific Corp., Kansas City, Mo.) should be readily available in case pus is expressed. The catheter tip should be cultured upon removal. It is important to realize that the usual procedure of immersing the amputated catheter tip in broth is frequenty associated with false positive cultures. Thus, either semiquantitative or quantitative techniques should be used. The simplest of these consists of rolling a 5 cm segment of the catheter tip across the surface of a blood agar plate. The growth of more than 15 colonies on the plate correlates with >105 organisms per gram in the catheter wound. These titers are similar to those found in other infected wounds and suggest the presence of venous infection. The infusion bottle should be inspected for cracks, precipitates, or turbidity, and the infusion fluid should be cultured. The nature and lot numbers of any suspect product should be recorded. Two blood cultures should be obtained by independent venipuncture from separate veins. If fungemia is suspected, each blood culture should include a biphasic bottle. If the patient is already receiving antimicrobial agents, the blood cultures should be diluted (20:1) or an antibiotic removal device used. A new infusion device with apparatus may be placed at a different site if necessary to reestablish IV therapy. If pus is expressed from the IV site, it should be Gram stained. Exploratory venotomy should be considered whenever pus is found. The fundi should be checked for focal retinal lesions. Although bacteremia may resolve after removal of the IV device, antimicrobials should be administered to septicemic patients. A penicillinase-resistant semisynthetic penicillin and an aminoglycoside active against the common, multiply resistant, nosocomial gram-negative bacilli are appropriate unless otherwise indicated by the results of the Gram stain. When fungemia is suspected, antimicrobial agents, corticosteroids, and antimetabolites are discontinued if possible. Patients must be followed daily for new evidence of septic thrombophlebitis or for evidence of other latent foci of infection. In conclusion, the early recognition of IV-related infection with adherence to these guidelines should help decrease the morbidity and mortality associated with such infections. Proper procedures for insertion and maintenance hopefully will make infusion-related infections an uncommon phenomenon. 138 references are cited.
Contamination potential of 3-in-1 TPN noted.
- Millerl
The growth of Candida albicans in nutritive solutions given parenterally.
- O 'connellrc Rosolja Brennanmf
- Knudsinr
Candida and Torulopsis.
- Braudea
Commitment to germ tube or bud formation during release from stationary phase in Candida albicans.
- Mitchelllh Solldr