Pamela D. Young, PharmD
Infectious Diseases Antimicrobial Clinical University of Louisville Hospital Louisville, Kentucky NOTE for opening page: This chapter contains information presented by Patricia A. Montgomery and Laura A. Cornish in Chapter 68 of the 2002 edition of the APIC Text of Infection Control and Epidemiology. ABSTRACT
Patient morbidity and mortality can result from contaminated
pharmaceuticals. Pharmacy is responsible for preparation and
storage of most sterile medication. It may be necessary for
pharmacy personnel to participate in identifying patients who
have received specific products associated with epidemics.
Pharmacy personnel are responsible for coordinating recalls of
pharmaceutical preparations, such as occurs in cases of
intrinsic contamination. The pharmacy department should participate
in multidisciplinary activities such as quality assurance
teams, infection control committees, and antimicrobial use programs
to ensure appropriate preparation and use of pharmaceuticals.
Risks associated with contamination of sterile products
Modes of contamination of sterile pharmaceutical products Methods for preventing contamination of sterile products Pharmacy responsibilities involving antimicrobial control
Patient morbidity and mortality can result from contaminated
pharmaceuticals. Pharmacy is responsible for preparation and
storage of most sterile medication. It may be necessary for
pharmacy personnel to participate in identifying patients who
have received specific products associated with epidemics.
Pharmacy personnel are responsible for coordinating recalls of
pharmaceutical preparations, such as occurs in cases of
intrinsic contamination. Other responsibilities of pharmacy
departments may include managing intravenous (IV) therapy
teams, compounding pharmaceuticals for patients receiving
home IV therapy, and compounding enteral nutrition products.
The pharmacy department provides oversight of the safe use
of medications in other areas of the institution (e.g., inspections
for outdated medication and monitoring of refrigerated
medication storage space). The pharmacy also provides information
on pharmaceuticals including indications, dosage, route
of administration, contraindications, adverse effects, drug interactions,
and proper storage. Pharmacy personnel are not at
high risk for occupational exposure to infectious diseases
unless they are involved in direct patient care, such as during
cardiac arrest response. The pharmacy should work
with infection control departments in managing
employee exposure to contagious patients and selection
of germicides. Pharmacists may be involved in
advocating and administering immunizations (e.g., influenza
and pneumococcal vaccines). The pharmacy
department should participate in multidisciplinary activities
such as quality assurance teams, infection control
committees, and antimicrobial use programs to ensure
appropriate preparation and use of pharmaceuticals.
Contamination of infusates is an uncommon cause of
infections, but may result in epidemics.1 Intrinsic contamination
(that which occurs during the manufacturing
process) and extrinsic contamination (that which occurs
subsequent to manufacturing, during the admixture
process or while the infusate is in use) of infusates are
a less frequent cause of infection than cannula-related
contamination but are more likely to result in bacteremia
and septic shock.1 Intrinsic and extrinsic contamination
are differentiated based on epidemiologic data.
Most nosocomial epidemics of infusion-related septicemia
resulting from intrinsic or extrinsic contamination
are caused by aerobic gram-negative bacteria.2
Pathogens implicated include the Enterobacteriaceae
such as Klebsiella, Enterobacter, Serratia spp. and
Citrobacter freundii, Burkholderia cepacia and Ralstonia
Intrinsic contamination of infusate has led to epidemics
of nosocomial sepsis.2,3-5 Intrinsic contamination of
parenteral medications with endotoxin caused an epidemic
of clinical sepsis in a newborn nursery.6 Epidemics
of Candida parapsilosis and Candida albicans
fungemia have been related to use of contaminated parenteral
nutrition (PN).7-9 Epidemics of septicemia
caused by Staphylococcus saprophyticus and Enterobacter
have resulted from contamination of
PN admixtures during compounding or storage.10,11
Clusters of postoperative infections have been associated
with extrinsic contamination of propofol, an intravenous
hypnotic agent in a 1% lipid emulsion;
organisms isolated include Staphylococcus aureus,
Candida albicans, Moraxella osloenis, Enterobacter
and Serratia marcescens.12-14 An outbreak
of Serratia marcescens and Enterobacter
bacteremia in a surgical intensive care unit was
traced to extrinsic contamination of the parenteral narcotic
fentanyl by a respiratory therapist who was drug
In-use IV fluids have contamination rates of 1.9 to
7.8%.16-19 The most common organism found is coagulase-
negative staphylococci. In addition, free endotoxin was found in 2.5%.18 In-use syringes of propofol have shown contamination rates of 19/376 (5.1%) and 18/302 (5.6%).20,21 Specific microorganisms have the ability to proliferate in different fluids. Klebsiella, Serratia, and Enterobacter species and Burkholderia cepacia can multiply in 5% dextrose.1 Candida albicans can grow slowly,1 while Staphylococcus, Proteus, Escherichia coli, Herellea and Pseudomonas aeruginosa die slowly in dextrose. 22 Burkholderia cepacia, Pseudomonas aeruginosa, Acinetobacter and Serratia will grow in distilled water.1 Pseudomonas aeruginosa, Enterobacter and Serratia can grow in lactated Ringer's solutions. 1 Microbial growth, with the exception of Candida species, is possible in 0.9% sodium chloride.23 Fungi such as C. albicans and Torulopsis glabrata can grow in PN fluids, albeit very slowly; proliferation did not occur when solutions were stored at 4_C for 7 days.24 The growth of most bacteria is inhibited in PN solutions. The addition of albumin to PN solutions increases the potential for bacterial and fungal growth.7,25 Staphylococcus aureus, E. coli, E. cloacae, P. aeruginosa, and C. albicans grow in 10% fat emulsion solution.23,26,27 Staphylococcus epidermidis, C. albicans, and E. coli survive in total nutrient admixtures (TNA), in which fat emulsion is combined with dextrose and amino acid mixtures.28 P. aeruginosa, S. aureus, S. epidermidis, Enterococcus faecalis, and Group JK Corynebacterium displayed greater growth in TNAs as compared to PN fluids.29 Propofol supported the growth of S. aureus, E. faecalis, P. aeruginosa, and C. albicans; for P. aeruginosa and E. faecalis, a bactericidal period was followed, after 48 hours, by increasing growth.30 Preparations of midazolam HCl, morphine sulfate, fentanyl citrate, bupivacaine HCl, atracurium besylate, vecuronium bromide, epinephrine, dopamine, dobutamine, norepinephrine, and sodium nitroprusside in normal saline and 5% dextrose in water were bactericidal for S. aureus, E. faecalis, P. aeruginosa, and E. coli and did not support growth of C. albicans at room temperature over 48–72 hours.30 Contamination of other pharmaceutical products has led to infections. An outbreak of B. cepacia caused by contamination of multidose albuterol vials was linked to poor infection control practices, including respiratory therapists carrying vials in their pockets for several days. The pH of some solutions tested was not within the recommended range, and the concentration of preservative fell from baseline after 5 days.31 Intrinsically contaminated saline solution used for respiratory therapy has caused clusters of R. pickettii respiratory tract colonization.32,33 Use of contaminated multidose ophthalmic containers have resulted in S. marcescens keratitis34 and P. aeruginosa corneoscleritis;35 the organisms were cultured from the container but not from the solution itself.34,35 Bacteria were cultured
from 82/638 in-use multidose ophthalmic solutions;36
on the other hand, 81 opened multidose ophthalmic
medications were tested, and no contamination was
found.37 Irrigation with a cardioplegic solution contaminated
with E. cloacae led to an outbreak of sepsis.38
Intrinsic contamination of a non-FDA-approved
product labeled "adrenal cortex extract" caused a
series of cases of Mycobacterium abscessus abscesses
in patients who received intramuscular injections.39
Contamination of enteral nutrition has been associated
with infections, including septicemia.40,41 Many microorganisms,
including gram-negative bacteria, gram-positive
bacteria and fungi, can proliferate in enteral
nutrition preparations.40,42,43 Mineral oil used for
bathing infants was contaminated with Listeria monocytogenes,
leading to an outbreak of neonatal listeriosis.
Preparation of IV products in areas outside the pharmacy,
in areas not providing a class 100 environment
(no greater than 100 particles per square foot), has led
to various bloodstream infections. Batch preparation of
propofol syringes outside a laminar-airflow hood was
associated with S. aureus bloodstream infections.45 E.
septicemia resulted from preparation of
heparin infusions in an area not specifically designed
for such use.46 An outbreak of B. cepacia sepsis
resulted from preparation of heparin infusions for
several patients using a single 500-mL bag of dextrose,
which was stored near a sink.47
Most IV-related infections result from microbial contamination
of the cannula and the cannula wound.1,2
Improper aseptic technique has been associated with
epidemics. Failure to employ aseptic technique during
preparation and administration of propofol combined
with inherent properties of this product contributed to
extrinsic contamination and resulted in postsurgical
Several epidemics have been traced to use of contaminated
multidose vials (MDVs), including an outbreak of
fulminant hepatitis B in a hospital that was apparently
due to contaminated heparin flush solution.48 Subcutaneous
Mycobacterium chelonei abscesses resulted
from contamination of diphtheria-pertussis-tetanuspolio
(DPTP) vaccine.49 Contamination of diphtheriapertussis-
tetanus-polio vaccine was implicated in two
outbreaks of group A streptococcal abscesses.50 Septic
arthritis resulted from intra-articular injections of MDV
methylprednisolone contaminated with B. cepacia.51
Contaminated MDVs were the most likely source of outbreaks
of hepatitis C virus infections.52
Contamination of in-use vials is rare, according to
recent studies.53,54 MDVs were tested for bacterial contamination during a two-phase study: during phase I there was a policy in place to discard MDVs after 14 days, and during phase II, they were discarded after 3 months. No contamination was found during either phase.55 An examination of 864 vials in use for up to 402 days found no contamination. The mean duration of use was 18 days, and only 13% were in use for more than 30 days.53 One hundred ninety-seven MDVs were collected that had been entered 1 to 10 times. No bacterial or fungal growth was found.56 Cultures from 8 of 68 insulin vials in use for a mean of 111 days grew Corynebacterium species or S. epidermidis; when recultured, five-eighths did not show growth. None of the positive cultures were associated with infections. No endotoxin was found in any of the samples.57 Sixty-nine in-use MDVs were collected; no bacterial contamination was identified, but one vial was contaminated with red blood cells.54 For the most part, the contents of MDVs, including preservatives, diluent, and the drug itself do not support microbial growth.58-60 Thirteen strains of microbes were used to deliberately contaminate MDVs of insulin, lidocaine, methohexital sodium, potassium chloride, procainamide, sodium thiopental, sodium heparin, and succinylcholine. Procainamide and methohexital were sterile within 24 hours; in lidocaine there was survival and even proliferation of some gram-negative aerobic bacteria. All others killed the organisms slowly or allowed only limited survival. Survival of microbes was not correlated with the presence of preservatives.60 Atropine, lidocaine, and cyanocobalamin were contaminated with S. aureus, P. aeruginosa, E. coli, and S. marcescens. The atropine and lidocaine solutions were sterile within 24 hours at room temperature. S. aureus in cyanocobalamin was killed slowly.58 Undiluted vials of midazolam HCl, morphine sulfate, fentanyl citrate, bupivacaine HCl, atracurium besylate, vecuronium bromide, epinephrine, dopamine, dobutamine, norepinephrine, and sodium nitroprusside were bactericidal for S. aureus, E. faecalis, P. aeruginosa, and E. coli and did not support growth of C. albicans at room temperature over 48–72 hours.29 Single-dose vials of gadolinium-based contrast media were inoculated with S. aureus, S. epidermidis, Corynebacterium jeikeium, Bacillus, Serratia odorifera, Xanthomonas maltophilia, or C. albicans and stored at room temperature or at 4_C. All organisms except S. odorifera persisted at 48 hours; S. aureus, S. epidermidis, and C. jeikeium were still present at 7 days.61 Most experimentally contaminated MDVs of anesthetic agents became sterile within 24 hours.59 Human immunodeficiency virus (HIV) was detectable Introduction I II III IV V VI VII VIII IX X XI XII XIII XIV XV Index up to four hours following deliberate contamination of MDVs of lidocaine containing epinephrine.62 MDVs were deliberately contaminated by several different methods. These methods were: entering the vial
without first swabbing, touching the rubber septum to
the skin, swabbing the rubber septum with an alcohol
wipe that had been dipped into a solution of 107 CFU
of bacteria, leaving the contaminated wipe on the
septum for 20 minutes, contaminating the needle with
the bacterial solution before withdrawing the medication,
and adding 0.1 mL of the bacterial solution to the
vial. With the first three methods, little or no growth
occurred. For the last three methods, almost all vials
showed heavy growth.56 Insulin vials deliberately contaminated
with S. aureus and P. aeruginosa were
sterile by 24 hours at room temperature; P. aeruginosa
was killed more slowly at 4_C.57 Contaminated
vials could be pathogenic even if sterile; following deliberate
contamination with B. (Pseudomonas) cepacia, a
vial of lidocaine had endotoxin, as did a vial of insulin
contaminated with Enterococci.60 Equipment used in
preparing intravenous admixtures can be a source of
Methods for Preventing Contamination of
Sterile Products
The Centers for Disease Control and Prevention (CDC)
recommends all parenteral fluids be prepared in the
pharmacy using a laminar-airflow hood.63 The Intravenous
Nursing Society Standards of Practice recommends
that an IV admixing program be established and
conducted under the direction of the pharmacy. When
nurses prepare IV admixtures, they should do so with
the use of a laminar-airflow hood.64
All sterile products should be prepared in a Class 100
environment,65 which can be obtained with the use of
a certified vertical- or horizontal-laminar-airflow hood.
Laminar-airflow hoods should be operated continuously.
Before processing products in the hood, it
should be in operation for a period of time long
enough to purge room air from the work area. All
work should be done at least 6 inches inside the hood.
The work surface and all accessible interior surfaces of
the hood should be disinfected with an appropriate
agent before work begins and periodically thereafter.
Exterior surfaces of the hood should be cleaned periodically.
The American Society of Health-System Pharmacists
(ASHP) recommends that laminar-airflow hoods
be certified biannually or when they are relocated.65
Certification should be performed by a qualified contractor.
In order to minimize the risk of contamination, sterile
products should be prepared in an area functionally
separate from other areas. The ASHP Guidelines on
Quality Assurance for Pharmacy-Prepared Sterile

Products65 recommends that the hood be situated in a
"controlled area" that meets either class 100,000 (no
greater than 100,000 particles per square foot) or
10,000 conditions (depending of the risk level of the
products being compounded) for acceptable airborne
particle levels. Class 10,000 conditions (no greater than 10,000 particles per square foot) can usually be met without use of a clean room.67,68 The sterile product preparation area should be one in which airflow and personnel traffic are limited. The ASHP recommends using a "limited access" area, separate from other pharmacy areas. This could be achieved by using a separate room or partitioned area. The materials surrounding the sterile preparation area should be nonparticle shedding. Particle-generating items such as cardboard boxes should not be stored in the area surrounding the hood. Air ducts and vents should not interfere with the airflow in the preparation area. The use of special walls, flooring, and ceilings (clean rooms) is not necessary. However, use of materials such as carpeting, drapes, and other particulate generating material is not acceptable. Personnel preparing sterile products should consider wearing special clothing covers that generate low amounts of particles. The ASHP65 recommends use of protective clothing covers including gowns, masks, and coverings for head and facial hair. However, at least one study has shown that special dress does not affect contamination rates.69 The sterile product preparation area should have handwashing facilities with hot and cold running water. Personnel should clean hands and forearms with an antimicrobial- containing soap or detergent before preparing sterile products. Eating, drinking, and smoking should not be allowed in the preparation area. The containers of the ingredients used for compounding the sterile product should be inspected for defects, expiration date, and product integrity before use. If the product is defective or has expired, it should not be used. Defective products should be promptly reported to the FDA.70 The rubber stoppers of containers should be wiped or sprayed with 70% alcohol before entry. The ASHP recommends that the entire surface of ampuls, vials, and container closures be disinfected appropriately before placement in the laminar-airflow hood.65 Automated devices used for compounding sterile products that are placed in the laminar-airflow hood should first be disinfected. Personnel should avoid touch contamination of sterile supplies. In 2002, five cases of Exophiala dermatitidis infection associated with injectable methylprednisolone acetate were reported to the CDC. The methylprednisolone had been prepared at a compounding pharmacy later found to have improper performance of an autoclave with no written procedures for autoclave prepara- Introduction I II III IV V VI VII VIII IX X XI XII XIII XIV XV Index tion, no testing for sterility or appropriate checking of quality indicators, and inadequate clean room practices as outlined in the ASHP guidelines for pharmacy-prepared products. Four patients developed meningitis after epidural injections, resulting in one death, and one patient developed sacroiliitis after intra-articular injections. Cases occurred as late as 152 days following an injection.71 Several factors must be considered in assessing the sterility of MDVs.72,73 The aseptic technique of individuals likely to enter specific vials is an important factor in determining sterility; improper aseptic technique has been identified in healthcare workers.74,75 The environment in which the vial will be entered is also important, such as sterility of the environment where vials are entered (i.e., laminar-airflow hoods versus patient care units) and situations under which vials are opened (e.g., MDVs on cardiac arrest carts are often entered without careful attention to aseptic technique and should be discarded after the first use).73,76 The U.S. Pharmacopoeia (USP) procedure for testing effectiveness of preservatives in MDVs does not require killing of all microorganisms but rather inhibition of proliferation of the microorganisms.76 The concentration of preservatives cannot be increased to unsafe levels.50 Many drug preparations appear to have sterilizing properties irrespective of the presence of preservatives.5 The effects of refrigeration on the bactericidal activity of preservative in MDV should be considered in setting policy.58 Solutions containing preservatives (phenol, methylparaben, and benzyl) and inoculated with S. aureus, P. aeruginosa, E. coli, and S. marcescens show persistence of bacteria longer under refrigeration than at room temperature.58,64 The number of entries may affect sterility of MDVs; however, there is no practical way to document this. In addition, frequent use may cause vials to be used up more rapidly, thereby actually reducing the risk of infection.53 Setting time limits after first opening can help ensure sterility and stability: 1. Manufacturers' expiration dates apply to stability and sterility of unopened vials. 2. There are no specific guidelines with respect to expiration of opened MDVs.63,73 The USP considers "any time limit put on the use of a multipledose vial after its first opening as strictly arbitrary." 73 3. Discarding MDVs after one use is probably not necessary. 4. Some sources recommend dating all opened vials, although there is no evidence that dating vials has any effect on sterility.53,54 5. Expiration of vials may need to vary according to other factors that affect sterility. The CDC recommends use of single-dose vials whenever possible for admixture of parenteral products.63 However, this may not be practical for IV admixture programs for reasons of economy and efficiency. When MDVs are used, the CDC recommends refrigerating the vials after opening if recommended by the manufacturer, cleaning the rubber diaphragm of the vial with alcohol before inserting a device into the vial, using a sterile device each time a vial is accessed, and avoiding touch contamination of the device before penetrating the rubber diaphragm. The MDV should be discarded when empty, when suspected or visible contamination occurs, or when the manufacturer's stated expiration date is reached.63 The final sterile product should be examined for any leaks, cracks, turbidity, or particulate matter. Bacterial growth may not be obvious, even in concentrations of 106/mL.22,63 The ASHP65 recommends a label be attached to all admixed parenterals and include the following information: 1. For patient-specific products: the patient's name and any other appropriate patient identification (e.g., location, identification number); for batch-prepared products: control or lot number 2. All solution and ingredient names, amounts, strengths, and concentrations (when applicable) 3. Expiration date and time, when applicable 4. Prescribed administration regimen, when appropriate (including rate and route of administration) 5. Appropriate auxiliary labeling (including precautions) 6. Storage requirements 7. Identification of the responsible pharmacist (and technician) 8. Device-specific instructions (when appropriate) 9. Any additional information, in accordance with state or federal requirements Storage of pharmaceuticals that are to be used to admix parenterals should be according to manufacturers' recommendations. Admixed parenterals may be stored in the refrigerator for up to 1 week, providing that refrigeration begins immediately after preparation and is continuous. Stability of ingredients may dictate a shorter storage time. The ASHP indicates that, depending on the sterile product preparation procedures used and the storage temperature, the admixed parenteral products may be stored for longer periods of time.6 Introduction I II III IV V VI VII VIII IX X XI XII XIII XIV XV Index The CDC has not made recommendations for the hang time of IV fluids (including nonlipid-containing parenteral nutrition fluids). Lipid-containing PN fluids should be completed within 24 hours of hanging the fluid.63 The CDC recommends that infusion times for lipid emulsions not part of a total nutrient admixture should be no more than 12 hours.63 However, some manufacturers of lipid emulsions support a 24-hour hang time.77 The manufacturers of propofol recommend that the drug be stored at room temperature; refrigeration is not recommended. If the drug is used directly from the prefilled syringe or vial, it should be used within 12 hours. Tubing and any unused portions of propofol vials should be discarded after 12 hours. However, if propofol is transferred to a syringe or other container prior to administration, the drug should be discarded and administration lines changed after 6 hours. Strict aseptic technique must be maintained in handling even though a preservative (EDTA or sodium metabisulfite) has been added.78 The pharmacy should monitor for appropriate storage of pharmaceuticals throughout the institution. Routine
inspections should be performed to ensure that expired
medications are removed from patient care areas and
disposed of properly. Temperatures of refrigerators
and freezers used to store pharmaceuticals should be
closely monitored and recorded daily.
For preparations given a high risk level, the ASHP65
recommends establishing criteria for monitoring the
environment, including air quality and work surfaces.
The ASHP65 recommends sterilization and quarantine
for high-risk products; efficacy of the sterilization
process should be validated. The ASHP recommends
that quality assurance procedures be developed to validate
aseptic technique for each person preparing
sterile products. Revalidation should occur annually or
"whenever the quality assurance program yields an
unacceptable result, and whenever unacceptable techniques
are observed."65
Pharmacy Responsibilities involving
Antimicrobial Control
Concerns about resistance causing increased morbidity,
mortality, and costs of healthcare have led to recommendations
to control antimicrobial use.79,80 Multidisciplinary
groups, including pharmacists, should establish
a system for monitoring resistance and antibiotic
usage, establish practice guidelines and other policies
to control the use of antibiotics and respond to data
from the monitoring system, and measure outcomes to
evaluate the effectiveness of policies. Microbiologists
should work with infectious disease clinicians, pharmacists,
hospital epidemiologists, infection control profes-
sionals, and representatives of clinical departments to
choose the drugs that will be tested and routinely
reported. Specific responsibilities for pharmacy personnel
include generation and analysis of data to determine
compliance with restriction policies, participation
in development of programs for formulary and antimicrobial
controls, responsibility for computer medication
order entry systems, and in collaboration with physicians,
patient-specific recommendations for optimal
antimicrobial use.
Pharmacy is responsible for preparation and storage of
most sterile medication. The pharmacy department
should participate in multidisciplinary activities such as
quality assurance teams, infection control committees,
and antimicrobial use programs to ensure appropriate
preparation and use of pharmaceuticals and sterile
1. Maki DG, Mermel LA: Infections due to infusion therapy. In
Bennett JV, Brachman PS, editors. Hospital infections, ed 4, Boston, 1998 Little, Brown and Company, pp. 689–724 2. Centers for Disease Control and Prevention: Epidemiologic notes and reports nosocomial bacteremias associated with intravenous fluid therapy, MMWR 20(Suppl 9):81–82, 1971 3. Phillips I, Eykyn S. Laker M: Outbreak of hospital infection caused by contaminated autoclaved fluids, Lancet 1:1258–1260, 1972 4. Fernandez C, Wilhelmi, I, Andradas E: Nosocomial outbreak of Burkholderia pickettii infection due to a manufactured intravenous product used in three hospitals, Clin Infect Dis 22: 1092–1095, 1996 5. Felts SK, Schaffner W, Melly MA, Koenig MG: Sepsis caused by contaminated intravenous fluids, Ann Intern Med 77:881–890, 1972 6. Centers for Disease Control and Prevention: Clinical sepsis and death in a newborn nursery associated with contaminated parenteral medications, MMWR 47:610–612, 1998 7. Plouffe JF, Brown DG, Silva J, et al: Nosocomial outbreak of Candida parapsilosis fungemia related to intravenous infusion, Arch Intern Med 137:1686, 1977 8. Solomon SL, Khabbaz RF, Parker RH, et al: An outbreak of Candida parapsilosis bloodstream infections in patients receiving parenteral nutrition, J Infect Dis 149:98–102, 1984 9. Moro ML, Maffei C, Manso E, Morace G, Poponelli L, Biavasco F: Nosocomial outbreak of systemic candidosis associated with parenteral nutrition, Infect Control Hosp Epidemiol 11:27–35, 1990 10. Dugleux G, Le Coutour X, Hecquard C, Oblin I: Septicemia caused by contaminated parenteral nutrition pouches: the refrigerator as an unusual cause, JPEN 15:474–475, 1991 11. Llop JM, Manques I, Perez JL, Lopez SL, Tubau M: Staphylococcus saprophyticus sepsis related to total parenteral nutrition admixtures contamination, JPEN 17:575–577, 1993 12. Centers for Disease Control and Prevention: Postsurgical infections associated with an extrinsically contaminated intravenous anesthetic agent, MMWR 39:426–427, 433, 1990 13. Bennett SN, McNeil MM, Bland LA, et al: Postoperative infections traced to contamination of an intravenous anesthetic, propofol, N Engl J Med 333:147–154, 1995 14. Henry B, Plante-Jenkins C, Ostrowska K: An outbreak of Serratia marcescens associated with the anesthetic agent propofol, Am J Infect Control 29:312–315, 2001 15. Ostrowsky BE, Whitener C, Bredenberg HK, et al: Serratia marcescens bacteremia traced to an infused narcotic, N Engl J Med 346:1529–1537, 2002 Introduction I II III IV V VI VII VIII IX X XI XII XIII XIV XV Index 16. Gorbea HF, Snydman DR, Delaney A, Stockman J, Martin WJ: Intravenous tubing with burettes can be safely changed at 48-hour intervals, JAMA 251:2112–2115, 1984 17. Maki DG, Botticelli MS, LeRoy ML, Thielke TS: Prospective study of replacing administration sets for intravenous therapy at 48- vs 72-hour intervals, JAMA 258:1777–1781, 1987 18. Maki DG, Ringer M, Alvarado CJ: Prospective randomised trial of povidone-iodine, alcohol, and chlorhexidine for prevention of infection associated with central venous and arterial catheters, Lancet 33:339–343, 1991 19. Trautmann M, Zauser B, Wiedeck H, Buttenscho¨n K, Marre R: Bacterial colonization and endotoxin contamination of intravenous infusion fluids, J Hosp Infect 37:225–236, 1997 20. Bach A, Motsch J, Schmidt H et al: In-use contamination of propofol: a clinical study, Eur J Anaesth 14:178–183, 1997 21. Webb ASR, Roberts B, Breheny FX, Golledges CL, Cameron PD, van Heerden PV: Contamination of propofol infusions in the intensive care unit: incidence and clinical significance, Anaesth Intens Care 26:162–164, 1998 22. Maki DG and Martin WT: Nationwide epidemic of septicemia caused by contaminated infusion products. IV. Growth of microbial pathogens in fluids for intravenous infusion, J Infect Dis 131: 267–272, 1975 23. Kim CH, Lewis DE, Kumar A: Bacterial and fungal growth in intravenous fat emulsions, Am J Hosp Pharm 40:2159–2161, 1983 24. Goldmann DA, Martin WT, Worthington JW: Growth of bacteria and fungi in total parenteral nutrition solutions, Am J Surg 126: 314–318, 1973 25. Mirtallo JM, Caryer K, Schneider PJ, et al: Growth of bacteria and fungi in parenteral nutrition solutions containing albumin, Am J Hosp Pharm 38:1907–1910, 1981 26. Melley MA, Meng HC, Schaffner W: Microbial growth in lipid emulsions used in parenteral nutrition, Arch Surg 110:1479–1481, 1975 27. Crocker KS, Noga R, Filibeck DJ, et al: Microbial growth comparisons of five commercial parenteral lipid emulsions, JPEN 8: 391–395, 1984 28. Mershon J, Nogami W, Williams JM, Yoder C, Eitzen HE, Lemons JA: Bacterial/fungal growth in a combined parenteral nutrition solution, JPEN 10:498–502, 1986 29. Scheckelhoff DJ, Mirtallo JM, Ayers LW, et al: Growth of bacteria and fungi in total nutrient admixtures, Am J Hosp Pharm 43: 73–77, 1986 30. Graystone S, Wells MF, Farrell DJ: Do intensive care drug infusions support microbial growth? Anaesth Intens Care 25: 640–642, 1997 31. Hamill RJ, Houston ED, Georghiou PR, et al: An outbreak of Burkholderia (formerly Pseudomonas) cepacia respiratory tract colonization and infection associated with nebulized albuterol therapy, Ann Intern Med 122;ZS762–766, 1995 32. Centers for Disease Control and Prevention: Nosocomial Ralstonia pickettii colonization associated with intrinsically contaminated saline solution, MMWR 47:285–286, 1998 33. McNeil MM, Solomon SL, Anderson RL, et al: Nosocomial Pseudomonas pickettii colonization associated with a contaminated respiratory therapy solution in a special care nursery, J Clin Microbiol 22:903–907, 1985 34. Templeton WC III, Eiferman RA, Snyder JW, et al: Serratia keratitis transmitted by contaminated eyedroppers, Am J Ophthalmol 93:723–726, 1982 35. Alfonso E, Kenyon KR, Ormerod D, et al: Pseudomonas corneoscleritis, Am J Ophthalmol 103:90–98, 1987 36. Hovding G and Sjursen H: Bacterial contamination of drops and dropper tips of in-use multidose eye drop bottles, Acta Ophthal 60:213–222, 1982 37. Tamer HR, Sweet B and Ross MB: Use and sterility of multidose ophthalmic medications, Am J Hosp Pharm 51:500–502, 1994 38. Talbot GH, Miller DE, Doorley M, et al: Enterobacter cloacae-contaminated cardioplegic solution, Am J Infect Control 12: 239–244, 1984 39. Centers for Disease Control and Prevention: Infection with Mycobacterium abscessus associated with intramuscular injection of adrenal cortex, MMWR 45:713–715, 1996 40. Anderton A: Microbiological aspects of the preparation and administration of naso-gastric and naso-enteric tube feeds in hospitals— a review, Hum Nutr 37A:426–440, 1983 41. Casewell MW, Cooper JE, Webster M: Enteral feeds contaminated with Enterobacter cloacae as a cause of septicaemia, Br Med J 282:973–974, 1981 42. Bastow MD, Greaves P, Allison SP: Microbial contamination of enteral feeds, Hum Nutr Appl Nutr 36A:213–217, 1982 43. Gill KJ and Gill P: Contaminated enteral feeds, Br Med J 282: 1971, 1981 44. Schuchat A, Lizano C, Broome CV, et al: Outbreak of neonatal listeriosis associated with mineral oil, Pediatr Infect Dis J 10: 183–189. 1991 45. Kuehnert MJ, Webb RM, Jochimsen EM: Staphylococcus aureus bloodstream infections among patients undergoing electroconvulsive therapy traced to breaks in infection control and possible extrinsic contamination by propofol, Anesth Analg 85:420–425, 1997 46. Koerner RJ, Morgan S, Ford M, Orr KE, McComb JM, Gould FK: Outbreak of gram-negative septicaemia caused by contaminated continuous infusions prepared in a non-clinical area, J Hosp Infect 36:285–289, 1997 47. van Laer F, Raes D, Vandamme P et al: An outbreak of Burkholderia cepacia with septicemia on a cardiology ward, Infect Control Hosp Epidemiol 19:112–113, 1998 48. Oren I, Hershow RC, Ben-Porath E, et al: A common-source outbreak of fulminant hepatitis B in a hospital, Ann Intern Med 110:691–698, 1989 49. Borghans JG, Stanford JL: Mycobacterium chelonei in abscesses after injection of diphtheria-pertussis-tetanus-polio vaccine, Am Rev Respir Dis 107:1–8, 1973 50. Stetler HC, Garbe PL, Dwyer DM, et al: Outbreaks of group A streptococcal abscesses following diphtheria-tetanus toxoid-pertussis vaccination, Pediatrics 75:299–303, 1985 51. Kothari T, Reyes MP, Brooks N, et al: Pseudomonas cepacia septic arthritis due to intra-articular injections of methylprednisolone, Can Med Assoc J 116:1230–1232, 1977 52. Widell A, Christenssen B, Wiebe T et al: Epidemiologic and molecular investigation of outbreaks of hepatitis C virus infection on a pediatric oncology service, Ann Intern Med 130:130–134, 1999 53. Longfield R, Longfield J, Smith LP, et al: Multidose medication vial sterility: an in-use study and a review of the literature, Infect Control 5:165–169, 1984 54. Melnyk PS, Shevchuk YM, Conly JM, et al: Contamination study of multiple dose vials, Ann Pharmacother 27:274–278, 1993 55. de Silva MI, Hood E, Tisdel E, et al: Multidosage medication vials: a study of sterility, use patterns, and cost-effectiveness, Am J Infect Control 14:135–138, 1986 56. Sheth NK, Post GT, Wisniewski TR, et al: Multidose vials vs single-dose vials: a study in sterility and cost-effectiveness, J Clin Microbiol 17:377–379, 1993 57. Rathod M, Saravolatz D, Pohlod D, et al: Evaluation of the sterility and stability of multidose insulin vials used for prolonged periods, Infect Control 6:491–494, 1985 58. Lehmann DR: Effect of refrigeration on bactericidal activity of four preserved multiple-dose injectable drug products, Am J Hosp Pharm 34:1196–1200, 1977 59. Young JA, Collette TS, Brehm WF: Sterility of multiple dose vials after repeated use, Am Surg 24:811–814, 1985 60. Highsmith AK, Greenhood GP, Allen JR: Growth of nosocomial pathogens in multiple dose parenteral medication vials, J Clin Microbiol 15:1024–1028, 1982 61. Green KA, Mustachi, Kschoer K, Moro D, Blend R, McGeer A: Gadolinium-based MR contrast media: potential for growth of microbial contaminants when single vials are used for multiple patients, AJR 165:669–671, 1995 62. Druce JD, Locarnini SA, Birch CJ: Isolation of HIV-1 from experimentally contaminated multidose local anaesthetic vials, Med J Australia 162:513–515, 1995 63. Centers for Disease Control and Prevention: Guidelines for the prevention of intravascular catheter-related infections, MMWR 51: 1–26, 2002 64. Intravenous Nurses Society: Intravenous nursing standards of practice, J Intravenous Nurs 21:S1–S95, 1998 65. American Society of Health-System Pharmacists: ASHP guidelines on quality assurance for pharmacy-prepared sterile products, Am J Health-Syst Pharm 57:1150–1169, 2000 66. Bryan D, Marback RC: Laminar-airflow equipment certification: what the pharmacist needs to know, Am J Hosp Pharm 41: 1343–1349, 1984 Introduction I II III IV V VI VII VIII IX X XI XII XIII XIV XV Index 67. Myers CE: Misrepresenting an ASHP practice standard for commercial purposes, Am J Hosp Pharm 51:2107–2108, 1994 68. Trissell LA, Chandler SW, Anderson RW: Indoor air is nearly cleanroom quality [letter], Am J Hosp Pharm 50:1858, 1861, 1993 69. Brier KL, Latiolias CJ, Schneider PJ, et al: Effect of laminarairflow and cleanroom dress on contamination rate of IV admixtures, Am J Hosp Pharm 39;ZS1144–1147, 1982 70. Kessler DA: MedWatch: the new FDA medical products reporting program, Am J Hosp Pharm 50:1921–1936, 1993 71. Centers for Disease Control and Prevention: Exophiala infection from contaminated injectable steroids prepared by a compounding pharmacy—United States, July–November 2002, MMWR 51: 1109–1112, 2002 72. Moi S and Thornton JP: Time limit on multidose vials after initial entry, Hosp Pharm 26:805–809, 1991 73. Heller WM: Time limits on the use of opened multiple-dose vials, Am J Hosp Pharm 37:1610–1613. Letter, 1980 74. Plott RT, Wagner RF, Tyring SK: Iatrogenic contamination of multidose vials in simulated use, Arch Dermatol 126:1441–1444, 1990 75. Centers for Disease Control and Prevention: Improper infectioncontrol practices during employee vaccination programs, MMWR 42:969–971, 1993
76. Eggleston M: Use of multidose vials, Infect Control 4:358–359,
77. Brown DH, Simkover RA: Maximum hang times for IV fat emulsions
(letter), Am J Hosp Pharm 44:282,284, 1987
78. Propofol Product Labeling: Gensia Sicor Pharmaceuticals, Inc.
Irvine, CA, 2002
79. Shlaes DM, Gerding DN, John JF, et al: Society for Healthcare
Epidemiology of America and Infectious Diseases Society of
America committee on the prevention of antimicrobial resistance:
guidelines for the prevention of antimicrobial resistance in hospitals,
Infect Control Hosp Epidemiol 18:275, 1997
80. Cuncan RA: Controlling use of antimicrobial agents, Infect
Control Hosp Epidemiol
18:260–266, 1997
American Society of Health-System Pharmacists (ASHP):
Centers for Disease Control and Prevention (CDC): www.cdc.gov
Food and Drug Administration (FDA): www.fda.gov
Intravenous Nursing Society (INS): www.ins1.org
United States Pharmacopeial Convention, Inc. (USP): www.usp.org

Source: http://hica.jp/forum/yuekichosei/61Pharmacy.pdf


Pourquoi les effets de secondaires de l'antidiabétique orale Avandia (roziglitazone) de sont-ils passés inaperçus en Executive summary In a context where the French pharmaceutical industry is buffeted by scandals and molecules in the hot seat. We would like to return to the information processing of the Avandia®

Pp150722 1263.1273

The Stromal Chloroplast Deg7 Protease Participates inthe Repair of Photosystem II after Photoinhibitionin Arabidopsis1[W][OA] Xuwu Sun, Tingjiao Fu, Ning Chen, Jinkui Guo, Jinfang Ma, Meijuan Zou, Congming Lu, and Lixin Zhang* Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy ofSciences, Beijing 100093, China Light is the ultimate source of energy for photosynthesis; however, excessive light leads to photooxidative damage and hencereduced photosynthetic efficiency, especially when combined with other abiotic stresses. Although the photosystem II (PSII)reaction center D1 protein is the primary target of photooxidative damage, other PSII core proteins are also damaged anddegraded. However, it is still largely unknown whether degradation of D1 and other PSII proteins involves previouslyuncharacterized proteases. Here, we show that Deg7 is peripherally associated with the stromal side of the thylakoidmembranes and that Deg7 interacts directly with PSII. Our results show that Deg7 is involved in the primary cleavage ofphotodamaged D1, D2, CP47, and CP43 and that this activity is essential for its function in PSII repair. The double mutants deg5deg7 and deg8 deg7 showed no obvious phenotypic differences under normal growth conditions, but additive effects wereobserved under high light. These results suggest that Deg proteases on both the stromal and luminal sides of the thylakoidmembranes are important for the efficient PSII repair in Arabidopsis (Arabidopsis thaliana).