ArticlePDF Available

Stability of benzylpenicillin during continuous home intravenous therapy

Authors:

Abstract and Figures

The aim of this study was to investigate the temperature profile of home intravenous (iv) antibiotic reservoirs and the stability of 16 megaunits of benzylpenicillin sodium in 120 mL of sodium chloride 0.9% at constant and variable temperatures. A Tinytag computerized thermometer recorded temperatures every minute in the home iv antibiotic reservoir pouches of nine patients over a 24 h period. Similar bags containing benzylpenicillin sodium (16 megaunits) were maintained either at a constant 36 degrees C, 26 degrees C or 21-22 degrees C or were worn in a pouch by five healthy volunteers for a 24 h period. Other bags were stored at 3-5 degrees C for 10 days. The bags were sampled at timed intervals and benzylpenicillin concentrations assayed by HPLC. Median temperatures recorded in the infusion bags worn by the nine patients were in the range 16.7-34.1 degrees C. For infusion bags maintained at 36 degrees C, 26 degrees C and 21-22 degrees C, the concentrations of benzylpenicillin dropped below 90% of the initial concentration at a mean time of 5 h 18 min, 12 h 54 min and 13 h 20 min, respectively, whereas for bags worn by the healthy volunteers the mean time for 10% loss of benzylpenicillin was 9 h 20 min. In contrast, at 3-5 degrees C, concentrations of benzylpenicillin only dropped below 90% of the initial concentration at 8 days. Significant temperature-dependent degradation of benzylpenicillin occurs during continuous home iv antibiotic programme infusions, which could result in loss of efficacy.
Content may be subject to copyright.
Journal of Antimicrobial Chemotherapy
DOI: 10.1093/jac/dkh146
Page 1 of 3
...................................................................................................................................................................................................................................................................
JAC © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved.
Stability of benzylpenicillin during continuous home
intravenous therapy
Jane W. A. Vella-Brincat
1
*, Evan J. Begg
1
, Kate Gallagher
2
, Carl M. J. Kirkpatrick
1,5
, Mei Zhang
1
,
Chris Frampton
3
and Stephen T. Chambers
2,4
1
Department of Clinical Pharmacology and
2
Department of Infectious Diseases, Christchurch Hospital, Christchurch,
New Zealand;
3
Department of Medicine and
4
Department of Pathology, Christchurch School of Medicine, Otago
University, Christchurch, New Zealand;
5
School of Pharmacy, University of Queensland, Queensland, Australia
Received 31 August 2003; returned 9 October 2003; revised 15 January 2004; accepted 16 January 2004
Objectives
: The aim of this study was to investigate the temperature profile of home intravenous (iv) anti-
biotic reservoirs and the stability of 16 megaunits of benzylpenicillin sodium in 120 mL of sodium chloride
0.9% at constant and variable temperatures.
Methods
: A Tinytag computerized thermometer recorded temperatures every minute in the home iv anti-
biotic reservoir pouches of nine patients over a 24 h period. Similar bags containing benzylpenicillin sodium
(16 megaunits) were maintained either at a constant 36
°
C, 26
°
C or 21–22
°
C or were worn in a pouch by five
healthy volunteers for a 24 h period. Other bags were stored at 3–5
°
C for 10 days. The bags were sampled at
timed intervals and benzylpenicillin concentrations assayed by HPLC.
Results
: Median temperatures recorded in the infusion bags worn by the nine patients were in the range
16.734.1
°
C. For infusion bags maintained at 36
°
C, 26
°
C and 2122
°
C, the concentrations of benzylpenicillin
dropped below 90% of the initial concentration at a mean time of 5 h 18 min, 12 h 54 min and 13 h 20 min,
respectively, whereas for bags worn by the healthy volunteers the mean time for 10% loss of benzylpenicillin
was 9 h 20 min. In contrast, at 35
°
C, concentrations of benzylpenicillin only dropped below 90% of the initial
concentration at 8 days.
Conclusions
: Significant temperature-dependent degradation of benzylpenicillin occurs during continuous
home iv antibiotic programme infusions, which could result in loss of efficacy.
Keywords: benzylpenicillin, home iv therapy, stability, temperature
Introduction
Benzylpenicillin sodium has been used internationally in home
intravenous (iv) therapy, where patients can be managed at home but
require prolonged therapy.
1–4
The use of home iv programmes
decreases length of hospital stay and has high patient acceptability.
1
However, much of the available data on antibiotic stability relates
to hospital application, where the antibiotics are infused at much
lower concentrations and temperatures than those during home iv
therapy.
2
The concentration of antibiotics in home iv pumps is higher,
as the volume of fluid that can be given is restricted by the size of the
pump reservoir. Similarly, the temperatures reached during the home
iv therapy are likely to be higher than those in the hospital setting, as
the reservoir of antibiotic is attached to the patient’s body. Con-
sequently, the literature relating to drug stability generated from
constant-temperature studies may not be relevant to the way in which
these agents are used in the home iv setting.
The purpose of this study was to document the profile of tempera-
tures in the antibiotic reservoir in the home iv therapy setting and to
determine the stability of benzylpenicillin sodium over this range and
also at refrigerator temperatures (3–5°C).
Materials and methods
A Tinytag (Gemini 2) computerized thermometer was used throughout
the study to record temperatures every minute. These data were then
downloaded to a Microsoft Excel spreadsheet.
The thermometer was carried next to the antibiotic reservoir in a
pouch for 24 h by nine consecutive patients recruited into the home iv
antibiotic therapy programme. Six patients kept the pouch attached to the
..................................................................................................................................................................................................................................................................
*Correspondence address. Department of Clinical Pharmacology, Christchurch Hospital, PO Box 4710, Christchurch, New Zealand.
E-mail: janevb@cdhb.govt.nz
Advance Access published March 10, 2004
by guest on June 2, 2013http://jac.oxfordjournals.org/Downloaded from
J. W. A. Vella-Brincat
et al.
Page 2 of 3
body around their waists for the whole 24 h. The remaining three patients
kept the pouch outside the bed at night. The groups are uneven as patients
were enrolled consecutively and asked to continue their lives as usual, to
gain a representative sample of actual practice in this group of patients.
The stability of benzylpenicillin sodium at room temperature
(2122°C), 26°C and 36°C was studied based on the temperatures
recorded in the pouches carried by the patients above. Triplicate plastic
(IntraVia, Baxter Healthcare Corporation) bags containing 16 megaunits
(9600 mg) of benzylpenicillin sodium (CSL) in 120 mL sodium chloride
0.9% (Baxter Healthcare Corporation) were made up in the pharmacy
sterile unit. The room temperature bags were stored on an open labora-
tory bench, and an incubator oven was used to maintain constant temper-
atures of 26°C and 36°C. Single (3 mL) samples were taken from each of
the bags immediately after dispensing (time 0) and every 2 h during
waking hours (06002200 h). All samples were stored at 80°C until
analysis. Each sample was analysed in triplicate by HPLC. A Tinytag
(Gemini 2) computerized thermometer was used to record temperatures
every minute at each of the temperatures.
Triplicate bags of benzylpenicillin sodium in 120 mL sodium chloride
0.9% were prepared as above and stored at 35°C for 10 days. Samples
(3 mL) were taken at time 0 and every 24 h for 10 days and stored at 80°C
until analysis by HPLC.
To simulate home iv therapy, five healthy volunteers each carried a
single plastic bag containing 16 megaunits of benzylpenicillin sodium in
120 mL of sodium chloride 0.9% in a home iv antibiotic therapy pouch for
two consecutive 24 h periods. During the first 24 h, the bag was worn
around the waist by the volunteers for the whole period, whereas during
the second 24 h period the bag was removed and placed by the bed at night.
Two consecutive 24 h periods were chosen to establish the difference in
temperature, and therefore stability, between positioning the antibiotic in
bed overnight and leaving it outside the bed. Samples (3 mL) were taken at
time 0 and every 4 h during waking hours, stored at 80°C until analysis
and analysed in triplicate for benzylpenicillin concentrations by HPLC.
The Students
t
-test (paired) was used to analyse the differences in
temperatures and the concentrations between the first and second 24 h
periods in the experiments where volunteers wore the pouches. To deter-
mine the time taken for benzylpenicillin concentrations to drop below
90% of the initial concentration, linear interpolation was used. The value
of 90% was chosen on the basis of clinical relevance, since a 10% loss of
potency was not considered significant.
Assay
Benzylpenicillin concentrations were determined using an HPLC
method. The standard curve (37.5, 75.0 and 150 mg/mL) was freshly
prepared in water using benzylpenicillin sodium powder (CSL). The
internal standard was mycophenolic acid (Sigma, St Louis, MO, USA).
Mycophenolic acid solution (50 µg/mL) was prepared by diluting the
stock solution (1.0 mg/mL) with water. To 20 µL of benzylpenicillin
standard or unknown sample, 2.0 mL of 50 µg/mL mycophenolic acid
solution was added. The mixture was vortexed and 50 µL aliquots were
injected into the HPLC system. HPLC analysis was performed on the
Agilent 1100 Series system equipped with a quaternary pump, a variable
wavelength detector set at 254 nm and an autosampler (Hewlett-Packard,
Waldbronn, Germany). An Aqua C
18
5 µm, 4 × 3.0 mm internal diameter
guard column and an Aqua C
18
5 µm, 75 × 4.6 mm internal diameter
analytical column (Phenomenex, Torrance, CA, USA) were used for
separation. Data were collected and analysed by the Agilent Chem-
Station (Hewlett-Packard, Waldbronn, Germany). The mobile phase was
a mixture of 0.05% phosphoric acid and acetonitrile (70:40, v/v) and the
flow rate was 1.5 mL/min. The standard curve was linear (
r
2
> 0.999) over
the range 37.5150 mg/mL. The intra-day coefficients of variation of the
assay were 5.8% and 3.0% at the concentrations 37.5 and 80 mg/mL,
respectively.
Results
Temperatures recorded in each of the nine patients bags are outlined
in Table 1. The three patients who took their bags off at night recorded
significantly lower median temperatures than those who did not
[20.2
°
C versus 32
°
C,
P
< 0.001 (Students
t
-test)].
The percentages of the initial concentrations of benzylpenicillin
sodium when stored at 36
°
C, 26
°
C and room temperature (2122
°
C)
for 24 h are shown in Figure 1. At 36
°
C, concentrations dropped to
below 90% of the initial concentration at a mean of 5 h 18 min. At
26
°
C, this occurred at 12 h 54 min and at room temperature this
occurred at 13 h 20 min. By 24 h, concentrations had dropped to 5%,
61% and 83% of initial concentrations at 36
°
C, 26
°
C and room
temperature (2122
°
C), respectively.
The median temperatures recorded in the infusion bags worn by
the five healthy volunteers were in the range 2831
°
C in the first 24 h
(in bed overnight) and 2628
°
C in the second 24 h (out of bed over-
night). The percentages of the initial concentrations of benzylpenicillin
from the bags worn by the five healthy volunteers are plotted in
Figure 2. The mean time at which the concentration dropped below
90% was 9 h 20 min (range 4 h 40 min to 15 h 22 min). Concentrations
dropped significantly more (to a mean of 27%) during the 24 h when
the bag was worn continuously than when the bag was left outside the
Table 1.
Temperatures (°C) recorded in the
home iv therapy pouches of the nine patients
studied over 24 h
a
Attached to body for full 24 h period.
Median Mean Range
1 16.7 16.5 9.926.6
2 20.9 21.8 16.727.4
323 23.314.532.6
4
a
31.1 29.4 18.836.1
5
a
31.1 30.9 24.533.7
6
a
31.8 29.7 19.134.9
7
a
31.8 31.6 1735.3
8
a
32.2 30.8 19.535.3
9
a
34.1 33.2 22.735.7
Figure 1.
Percentages of the initial concentrations of benzypenicillin stored at
36
°
C, 26
°
C and room temperature (2122
°
C) for 24 h (means
±
S
.
E
.
M
.).
by guest on June 2, 2013http://jac.oxfordjournals.org/Downloaded from
Benzylpenicillin stability
Page 3 of 3
bed at night (to a mean of 54%,
P
< 0.001). The difference between
the concentrations before bed and after bed as a percentage of initial
concentrations was statistically significant.
At refrigerator temperatures (35°C), benzylpenicillin concen-
trations only dropped below 90% of the initial concentration by day 8.
Discussion
The temperatures reached in the antibiotic reservoir during home iv
antibiotic therapy are sufficient to cause significant degradation of
benzylpenicillin, which could have clinical significance. In both
patients and healthy volunteers, over much of a 24 h period the anti-
biotic reservoirs were maintained at temperatures approximating to
body temperature. The highest temperature recorded when attached
to a body was 36.1°C.
When benzylpenicillin sodium was maintained at constant tempera-
tures of 2122°C (room temperature), 26°C and 36°C, significant
breakdown occurred, suggesting that benzylpenicillin sodium may
not be a good candidate for home iv antibiotic therapy using standard
delivery systems, especially if ambient or likely temperatures are
high.
Our results differ significantly from previous studies of the stability
of benzylpenicillin sodium in portable pump reservoirs.
1,3
These
studies found that at a constant temperature the percentages of
benzylpenicillin sodium left after 24 h were 83.9% at 37°C and
98.9%100.7% at 25°C, as compared with 5% and 61% observed in
this study at 36°C and 26°C, respectively. This may reflect differ-
ences in concentrations of solutions studied, pH of the solutions or
some other aspect of study design. Interestingly, though, our data
agree well with other data presented by Stiles
et al.
1
where in a speci-
ficity check they observed a drop to 68% of the initial concentration
after 24 h at 25°C. Unfortunately, the authors did not propose an
explanation for the apparent discrepancy between their two sets of data
on the stability of benzylpenicillin at 25°C. The concentration studied
here reflects the highest concentrations used in our clinical practice.
Although replicating the concentrations in the above studies would
have been useful, we chose to study a concentration applicable to our
clinical practice.
The lack of stability of benzylpenicillin sodium in the simulated
home iv therapy part of this study suggests that benzylpenicillin
sodium may not be sufficiently stable to be used as a 24 h continuous
infusion in this setting. As far as we are aware, no other studies of con-
centrations of benzylpenicillin during home iv therapy have been
published. The time at which concentrations dropped below 90% of
the initial concentration shows considerable inter- and intra-individual
variation, ranging from 4 h 40 min to 15 h 22 min (mean 9 h 20 min).
Concentrations of benzylpenicillin stored in the refrigerator (35°C)
remained above 90% of the initial concentration until day 8, suggesting
a refrigerated shelf-life of around 67 days. This indicates that the use
of insulated pouches, perhaps with freezer packs, may improve the
stability of benzylpenicillin during home iv therapy. If the temperature
in the pouch could be maintained lower than normal room temperature,
the stability of benzylpenicillin may be improved. In one study, the
use of such a pouch successfully extended the stability of ampicillin
infusions from 6 h to 24 h.
2
In summary, significant degradation of benzylpenicillin sodium
occurs at temperatures encountered in the reservoir solution during
home iv antibiotic programmes. This lack of stability of benzyl-
penicillin sodium suggests that it may be unsuitable for continuous
infusion in the home iv antibiotic therapy setting in uncontrolled con-
ditions. The implementation of a cool bag carrying system may
improve the stability of benzylpenicillin sodium and should be studied
further.
Acknowledgements
We would like to thank Peter Skidmore for his help with the electronic
thermometer. This research was funded by a Canterbury Medical
Research grant.
References
1.
Stiles, M. L., Tu, Y.-H. & Allen, L. V. (1989). Stability of cefazolin
sodium, cefoxitin sodium, ceftazidime and penicillin G sodium in portable
pump reservoirs.
American Journal of Hospital Pharmacy
46
, 1408–12.
2.
Stiles, M. L., Allen, L. V. & Prince, S. J. (1995). Stability of various
antibiotics kept in an insulated pouch during administration via portable
infusion pump.
American Journal of Health-System Pharmacy
52
, 70–4.
3.
Stiles, M. L. & Allen, L. V. (1997). Stability of nafcillin sodium,
oxacillin sodium, penicillin G potassium, penicillin G sodium and tobra-
mycin sulfate in polyvinyl chloride drug reservoirs.
American Journal of
Health-System Pharmacy
54
, 1067–70.
4.
Leggett, J. E. (2000). Ambulatory use of parenteral antibacterials.
Drugs
59
, 1–8.
Figure 2.
Percentages of the initial concentrations of benzylpenicillin from the
bags worn by five healthy volunteers (means
±
S
.
E
.
M
.).
by guest on June 2, 2013http://jac.oxfordjournals.org/Downloaded from
... Previous studies have demonstrated that medications reach higher temperatures than the manufacturers' 25°C guideline. [13][14][15] A frequently cited study performed on an electronic continuous ambulatory delivery device (CADD) found a mean solution temperature of 28.8°C and a maximum temperature of 30.9°C. 13 The conclusion from that study was that stability studies should be performed at temperatures higher than room temperature but lower than body temperature. ...
... Previous studies neither investigated nor commented on the initial temperature rise, implying a single constant temperature was used for investigation of the full 24-h run-out period. 13,14 One possible rationale for excluding the initial equilibration to ambient temperature change may be due to the convenience of replicating a less complex model within a laboratory. However, we believe that to appropriately investigate medications in warmer climates, the initial steady increase over the first 9.4 h should be replicated as close as possible within a laboratory setting. ...
Article
Background Stability data tested at 25°C may not be suitable for use in the tropics in the home intravenous infusions (Home‐IV) setting. A 24‐h solution temperature profile is needed to investigate medication stability in this setting. Aim This study investigated and mapped the solution temperature within the Baxter LV10 elastomeric infusor device in a tropical environment over a 24‐h period. Methods Volunteer patients from Home‐IV clinics in two tropical Australian cities wore elastomeric infusor devices for 24 h over the summer months. Temperature devices were inserted into the solution to directly log solution temperature. Results Solution temperature was >25°C 79.8% of the time. Mean time to inflection (temperature stops rising and begins fluctuating) was 9.4 h (95% confidence interval (CI) 8.6–10.2), with a maximum inflection point of 14.5 h. The mean (95% CI) temperature at inflection and after inflection was 30.6°C (29.8–31.5) and 29.5°C (29.3–29.6), respectively; the 90th percentile temperature after inflection was 32.5°C. Analysis of variance revealed a significant difference of 3.1°C between air‐conditioned and non‐air‐conditioned data (F1,28 = 13.06, p = 0.001). The 90th percentile temperature after inflection for non‐air‐conditioned data was 33.1°C. Conclusions Stability studies performed at 25°C are inappropriate for tropical regions. Possible factors contributing to the higher temperatures include body and ambient room temperature. We recommend that medications are tested in 24‐h elastomeric infusor devices in three steps: (1) refrigerated for up to 7 days; (2) steady increase from refrigerated to 34°C over 9 h; and (3) maintained at 34°C for the remaining 15 h. This more accurately reflects the temperature profile experienced in warmer climates. Furthermore, Home‐IV patients should be encouraged to remain in an air‐conditioned environment, or at least indoors, over the summer months to decrease the potential for antibiotic degradation.
... Antibiotic degradation in aqueous solution has been extensively studied in the chemical literature [15][16][17][18][19], and it is well-known that, under some conditions, antibiotics can degrade on timescales much shorter than a typical bacterial growth assay. There has been little work, however, on how quickly antibiotics degrade in standard laboratory growth media, such as those pH, with maximal stability around pH 4-5 for α-amino β-lactams (e.g. ...
Article
Full-text available
Laboratory assays such as MIC tests assume that antibiotic molecules are stable in the chosen growth medium—but rapid degradation has been observed for antibiotics including β-lactams under some conditions in aqueous solution. Degradation rates in bacterial growth medium are less well known. Here, we develop a ‘delay time bioassay’ that provides a simple way to estimate antibiotic stability in bacterial growth media, using only a plate reader and without the need to measure the antibiotic concentration directly. We use the bioassay to measure degradation half-lives of the β-lactam antibiotics mecillinam, aztreonam and cefotaxime in widely-used bacterial growth media based on MOPS and Luria-Bertani (LB) broth. We find that mecillinam degradation can occur rapidly, with a half-life as short as 2 hours in MOPS medium at 37°C and pH 7.4, and 4-5 hours in LB, but that adjusting the pH and temperature can increase its stability to a half-life around 6 hours without excessively perturbing growth. Aztreonam and cefotaxime were found to have half-lives longer than 6 hours in MOPS medium at 37°C and pH 7.4, but still shorter than the timescale of a typical minimum inhibitory concentration (MIC) assay. Taken together, our results suggest that care is needed in interpreting MIC tests and other laboratory growth assays for β-lactam antibiotics, since there may be significant degradation of the antibiotic during the assay.
... When performing an MIC assay, one 5 assumes that the antibiotic does not degrade over the timescale of the assay. Antibiotic 6 stability is also assumed in a host of other bacterial growth assays that are used to 7 determine antibiotic mechanism of action [2][3][4][5], interactions between antibiotics [6][7][8][9], 8 and evolution of antibiotic resistance [10][11][12][13][14]. 9 Antibiotic degradation in aqueous solution has been extensively studied in the 10 chemical literature [15][16][17][18][19], and it is well-known that, under some conditions, 11 antibiotics can degrade on timescales much shorter than a typical bacterial growth assay. 12 There has been little work, however, on how quickly antibiotics degrade in standard 13 laboratory growth media, such as those used for MIC assays. ...
Preprint
Full-text available
Laboratory assays such as MIC tests assume that antibiotic molecules are stable in the chosen growth medium - but rapid degradation has been observed for antibiotics, including β-lactams, under some conditions in aqueous solution. Degradation rates in bacterial growth medium are less well known. Here, we develop a 'delay time bioassay' that provides a simple way to estimate antibiotic stability in bacterial growth media. We use the bioassay to measure degradation half-lives of the β-lactam antibiotics mecillinam, aztreonam and cefotaxime in widely-used bacterial growth media based on MOPS and Luria-Bertani (LB) broth. We find that mecillinam degradation can occur rapidly, with a half-life as short as 2 hours in MOPS medium at 37°C and pH 7.4, and 4-5 hours in LB, but that adjusting the pH and temperature can increase its stability to a half-life around 6 hours without excessively perturbing growth. Aztreonam and cefotaxime were found to have half-lives longer than 6 hours in MOPS medium at 37°C and pH 7.4, but still shorter than the timescale of a typical minimum inhibitory concentration (MIC) assay. Taken together, our results suggest that care is needed in interpreting MIC tests and other laboratory growth assays for β-lactam antibiotics, since there may be significant degradation of the antibiotic during the assay.
... Our aims were to (1) To perform a systematic review of antibiotic stability data literature. (2) To determine if there are sufficient data to confirm >90% stability for commonly used, or historically used, antibiotics in OPAT in standard (20-25 o C) and warmer climates (34°C or above). ...
Article
Aim To determine if there are sufficient stability data to confirm appropriate prescribing of antibiotics commonly used in outpatient parenteral antimicrobial therapy (OPAT) in warmer climates. Data sources Four databases were systematically searched using the terms ‘beta-lactams’, or ‘antibiotics’, or ‘anti-bacterial agents’ and ‘drug stability’ or drug storage’ for studies specific to drug stability published between 1966 and February 2018. Study selection The search strategy initially identified 2879 potential articles. After title and abstract review, the full-texts of 137 potential articles were assessed, with 46 articles matching the inclusion and exclusion criteria included in this review. Results A large volume of stability data is available for the selected drugs. Stability data at temperatures higher than 25°C were available for several of the medications, however few drugs demonstrated stability in warmer climates of 34°C or higher. Only buffered benzylpenicillin, cefoxitin and buffered flucloxacillin were found to have stability data supporting OPAT in warmer climates. Sequential data, profiling the drug for an extended period in solution under refrigeration prior to the run-out period at the higher temperatures, are also lacking. Limitations This study was limited by including only peer reviewed articles. There may be further grey literature supporting the stability of some of the drugs mentioned. Conclusion There are insufficient stability data of antibiotic use in warmer climates. Studies to verify the stability and appropriate use of many antibiotics used in OPAT at standard room temperature and in warmer climates are urgently required. Several drugs in current use in the OPAT settings are lacking stability data. Implications Further research in this field is needed to develop structured evidence-based guidelines. Results of this review should be further compared with observed patient outcomes in current clinical practice.
Article
Introduction: The objectives of this study were to develop a stability-indicating high performance liquid chromatography (HPLC) assay for benzylpenicillin (BPC) in pharmaceutical fluids, and to investigate the stability of (i) isotonic citrate-buffered BPC solutions at the clinically relevant concentration of 30 mg/mL, and (ii) low concentration citrate-buffered BPC intravenous infusions (5-30 μg/mL). Methods: The stability of isotonic BPC solutions containing 3.4 or 7.2 mg/mL sodium citrate was compared against contemporary hypertonic solutions. The HPLC assay was shown to be stability-indicating following acidic, alkali, oxidative and elevated temperature stress testing. Results: After 7 d storage at 4 °C and 24 h at 35 °C, the concentrations of isotonic BPC 30 mg/mL solutions containing 3.4 and 7.2 mg/mL sodium citrate were 96% and 95% respectively, compared to day 0. After 3 d at 4 °C and 24 h at room temperature (22 °C), the concentrations of isotonic BPC solutions with 3.4 and 7.2 mg/mL sodium citrate were 99% and 96% respectively, compared to day 0. These data were comparable to the hypertonic solutions and meet pharmacopeial stability requirements. Low concentration BPC infusions showed 0.5% and 2.5% degradation after 24 h storage at 22 °C and 35 °C, respectively. Conclusions: The isotonic BPC 30 mg/mL formulation is simple to prepare and may offer clinical benefits in settings where hypertonic solutions are problematic. This study provides assurance that high- and low-dose isotonic BPC infusions are stable at room temperature and our findings may be applicable to in vitro studies of BPC.
Article
Introduction Benzylpenicillin and flucloxacillin are commonly used in outpatient parenteral antibiotic therapy (OPAT). Published evidence supporting the stability of buffered infusions, in a variety of devices and concentrations, using an Australian commercially available buffer, to suit a paediatric setting is desirable. The aim of this study was to determine if multiple concentrations of buffered benzylpenicillin and flucloxacillin, prepared in suitable infusion devices, exposed to a variety of temperatures, maintained stability. Methods Benzylpenicillin (15 and 60 mg/mL) and flucloxacillin (5 and 60 mg/mL) infusions in LV Elastomeric Infusor devices and sodium chloride 0.9% Viaflex bags were prepared as buffered and unbuffered solutions. Buffering was achieved by reconstituting antibiotic vials with sodium citrate 4%. Infusions were stored at 2–8°C for 6 days then 37°C for 24 h. Samples were taken on day 0, 1, 3, 6 and 7. The concentration, pH, colour and appearance were assessed at each time point. Results The concentration of all day 7 buffered benzylpenicillin samples was maintained between 97.70–100.36% and flucloxacillin 98.7–100.66% of the initial concentration. Unbuffered solutions did not retain antibiotic potency over the same study period. There was minimal pH change in buffered benzylpenicillin samples from 6.66 to 5.5 and flucloxacillin 6.58 to 6.19. There was no visual change in colour or appearance. Conclusion Buffered benzylpenicillin 15 and 60 mg/mL and flucloxacillin 5 and 60 mg/mL in LV Elastomeric Infusors and sodium chloride 0.9% Viaflex bags, appear chemically stable for 6 days refrigerated, and for a subsequent 24 h at 37°C.
Article
Over several decades, the economic situation and consideration of patient quality of life have been responsible for increased outpatient treatment. It is in this context that outpatient antimicrobial treatment (OPAT) has rapidly developed. The availability of elastomeric infusion pumps has permitted prolonged or continuous antibiotic administration by dint of a mechanical device necessitating neither gravity nor a source of electricity. In numerous situations, its utilization optimizes administration of time-dependent antibiotics while freeing the patient from the constraints associated with infusion by gravity, volumetric pump or electrical syringe pump and, more often than not, limiting the number of nurse interventions to one or two a day. That much said, the installation of these pumps, which is not systematically justified, entails markedly increased OPAT costs and is liable to expose the patient to a risk of therapeutic failure or adverse effects due to the instability of the molecules utilized in a non-controlled environment, instability that necessitates close monitoring of their use. More precisely, a prescriber must take into consideration the stability parameters of each molecule (infusion duration, concentration following dilution, nature of the diluent, pump temperature). The objective of this work is to evaluate the different means of utilization of elastomeric infusion pumps in intravenous antibiotic administration outside of hospital. Following a review of the literature, we will present a tool for optimized antibiotic prescription, in a town setting by means of an infusion device.
Article
Full-text available
“Antimicrobial stewardship” is a strategy that promotes the responsible use of antimicrobials. The objective of this paper is to focus on consolidated and more recent improvements in clinical strategies that should be adopted in hospitalized patients to ameliorate their infectious diseases’ outcome and to reduce the antibiotic resistance risk through judicious use of antibiotics. We present 13 common clinical scenarios, the respective suggested interventions and the explanations of the supporting evidence, in order to help clinicians in their decision-making process. Strategies including the choice of antibiotic and dose optimization, antibiotic spectrum narrowing (de-escalation), shortening of duration, shift to oral route or outpatient parenteral antibiotic (including elastomeric pumps), and biomarkers are described and discussed.
Article
Outpatient parenteral antibiotic therapies (OPAT) are increasingly used, as they are associated with numerous benefits for patients and society. However, as no control is made by the hospital pharmacy, OPATs are associated with misuse and iatrogenic and ineffectiveness risks.The present work aimed to update the guidelines developed by Longuet et al. (Med Mal Infect 2016 ; 46 : 242–268) on the preparation and administration modalities of OPATs.Based on available information sources, the present work provides prescribers and healthcare professionals with key data for the proper preparation and best administration modalities of intravenous antibiotics.
Article
The stability of cefazolin sodium, cefoxitin sodium, ceftazidime, and penicillin G sodium in prefilled drug reservoirs that were stored at -20°C for 30 days, thawed at 5°C for four days, and pumped at 37°C for one day was studied. Each antimicrobial agent was diluted with sterile water for injection to a concentration representative of the most common dosage when administered via a portable infusion pump. Ten milliliters of each drug solution was placed in individual glass vials to serve as controls, and volumes appropriate to deliver the designated dosages were loaded into the drug reservoirs. Triplicate reservoirs were prepared for each drug. One-milliliter samples from all containers were taken on days 0, 30, 31, 32, 33, 34, 34.5, and 35. All solutions were observed for color change and precipitation. Drug concentrations were determined using high-performance liquid chromatography. Leaching of the plasticizer diethylhexyl phthalate (DEHP) was analyzed by packed-column gas chromatography on days 0 and 35. No color change or precipitation was observed. No DEHP concentrations above 1 ppm were detected. More than 90% of the initial concentrations of each drug remained, except penicillin G sodium, which had a mean concentration of 83.9 +/- 0.5% at the end of the study. Cefazolin sodium, cefoxitin sodium, and ceftazidime in admixtures with sterile water for injection are stable under the conditions of this study. Penicillin G sodium should not be administered for more than 12 hours after such a cycle of freezing and thawing.
Article
Outpatient parenteral antimicrobial therapy (OPAT) offers increased patient comfort and convenience in appropriately selected patients who require parenteral antibacterial therapy, as well as opportunity for cost savings. Home-based programmes, with drugs being administered by the patient or the caregiver, have become the norm in the USA. Choice of drugs for OPAT is based on antimicrobial spectrum, dosage regimen, drug stability, toxicity profile, and cost. Over the past decade, availability of sophisticated programmable pumps has allowed a wider range of antimicrobial agents to be used in the ambulatory setting. The most popular antibacterial agents in OPAT programmes in the USA are vancomycin and beta-lactams.