Method for obtaining blood using iontophoresis

The present invention provides a method for obtaining blood from a patient which comprises: PA1 (a) iontophoretic delivery of a bacteriocidal effective amount of a bacteriocide through the patient's skin, and PA1 (b) obtaining blood through the skin at the site of the iontophoretic delivery. The invention is particularly advantages in reducing the effects of contaminants responsible for large numbers of false positives. This advantageous is beneficial not only to a patient who benefits from an accurate diagnosis, but is also beneficial economically by eliminating unnecessary hospital stays, testing, and consulting.

FIELD OF THE INVENTION 
The invention is the field of blood culturing. In particular, the invention 
is in the area of obtaining blood. 
BACKGROUND 
Contaminant blood cultures are common, representing up to half of all 
positive blood cultures. D. Bates et al., JAMA 265:363 (1991). 
Contaminants can in turn lead to unnecessary therapy, such as the 
administration of antibiotics, and additional testing and consulting. In 
addition, contaminated blood cultures can result in unnecessarily 
prolonged hospital stays. Such unnecessary procedures result in excess 
laboratory fees, diagnostic fees, pharmacy fees, physicians' fees, and 
hospital fees. Thus, in addition to inconvenience and potential harm to a 
patient, the true costs associated with contaminated blood cultures can be 
economically exorbitant. 
The increased costs associated with contaminated blood cultures underscores 
the importance of sterile technique when obtaining blood samples. 
Although the importance of sterile technique in the medical field, and in 
the area of blood sampling and culturing in particular has been known for 
some time, evidence as presented in the study by D. Bates et al. 
demonstrates a continued and urgent need for improvements in sterile 
techniques. 
Recent activity in the area of sterile techniques is evidenced in European 
Patent Application number 89301916.6 directed to anesthesia and antisepsis 
of the skin. In the European application the use of transdermal delivery 
of anesthetics having antimicrobial properties is disclosed. 
However, the need for sterile techniques for obtaining blood free of 
contaminants is still unmet. 
SUMMARY OF THE INVENTION 
The present invention provides a sterile technique for obtaining blood. The 
invention is a method for obtaining blood from a patient which comprises 
(a) iontophoretic delivery of a bacteriocidal effective amount of a 
bacteriocide through the patient's skin, and (b) obtaining blood through 
the skin at the site of the iontophoretic delivery 
Further embodiments of the invention include the iontophoretic delivery of 
anesthetics, enhancers, and the like along with the bacteriocide. 
Other embodiments of the invention include the topical administration of 
anesthetics, enhancers, and the like prior to the delivery of a 
bacteriocide. 
Preferred embodiments include the iontophoretic delivery of anesthetics as 
bacteriocides and the iontophoretic delivery of silver as a bacteriocide. 
The invention is particularly advantageous in that it provides both a 
sterile technique and an essentially bacteria free blood sample, which 
eliminates the problems associated with contamination, and a rapid 
sterilization of the area from which the blood sample is to be obtained. 
By obtaining sterile blood samples, erroneous additional testing, 
consulting, hospital stays, and exorbitant costs associated therewith are 
eliminated. The ability to obtain a sterile blood sample is particularly 
advantageous when a culture will be necessary. In addition, patients are 
afforded better and quicker diagnosis, which value includes greater peace 
of mind to all those involved. 
As used in this document, "patient" refers to animals, including humans, 
household animals such as dogs and cats, livestock such as cattle, horses, 
sheep, pigs, goats and rabbits, laboratory animals such as mice and rats, 
and zoo animals such as exotic species. "Bacteriocide" refers to any 
composition comprising an agent suitable for administration to a patient 
which is effective in substantially reducing the effects from bacteria, 
which effects will no longer create false positives to the point of 
interfering with sample interpretation. "Bacteriocidal effective amount", 
as used in this document, refers to that amount which results in a 
substantial reduction in the effect of bacteria contaminants in a blood 
sample, the primary effect being a reduction in false positives.

DETAILED DESCRIPTION OF THE INVENTION 
Blood collection techniques are routine for most hospital and physician 
personnel. Reference manuals on the practice and handling of laboratory 
specimens include J. Slockbower and T. Blumenfeld, "Collection and 
Handling of Laboratory Specimens," (J. P. Lippincott Company, Phila., Pa., 
1983) and F. Fischbach "A manual of laboratory diagnostic tests, third 
edition" (J. P. Lippincott Company, Phila., Pa., 1988). 
Blood collection means for withdrawing blood include collection tubes such 
as test tubes and capillary tubes, and needle and syringe means such as 
evacuated blood collection means such as a VACUTAINER system. 
The particular locale for obtaining a blood sample will depend on a variety 
of factors such as the amount of sample needed and the specifics of the 
individual. For example, blood typing or a crude cholesterol reading may 
require only a few drops of blood easily obtainable with a finger stick. 
However, a complete blood analysis may require several milliliters, most 
easily obtainable by venipuncture, for example, puncture of the 
antecubital vein. Sterility is most desired when a sample of blood is to 
be cultured. The preferred locale for obtaining blood samples from an 
infant is usually the heel or earlobe, while the preferred locale for an 
adult might be the arm or leg. The professional in charge of obtaining the 
blood sample is generally knowledgeable of the proper locale and proper 
amounts necessary for a particular need. 
The typical protocols for preparing patients for obtaining blood samples 
can be used in conjunction with the present invention. For example, the 
use of alcohols, povidone-iodine (Betadine), and warming. 
Once the amount of blood sample to be obtained is known and once the locale 
for obtaining the blood sample is chosen, the present invention can be 
practiced. 
There are a variety of iontophoretic devices which can be used to practice 
the invention. The particular device employed is not key. However, the 
ability to deliver a bacteriocide to the locale, both to the surface and 
into the skin, from which a blood sample is to be obtained is key. 
Generally, iontophoretic devices comprise at least two electrodes, an 
electrical energy source (e.g., a battery) and at least one reservoir 
which contains a composition to be delivered. Several iontophoretic 
devices are known, such as those disclosed in P. Tyle, Pharmaceutical 
Biosearch 3:318 (1986). Several recent United States patents describe 
iontophoretic devices such as J. Phipps et al. in U.S. Pat. No. 4,744,787 
and D. Sibalis in U.S. Pat. No. 4,808,152. 
The iontophoretic delivery of bacteriocides has several advantages. In 
particular, speed is greatly enhanced over topical or passive transdermal 
delivery methods. Depth of penetration is also enhanced and attained in 
less time than topical or passive transdermal delivery methods. The 
ability to obtain a rapid bacteriocidal effect is especially beneficial 
due to the fact that the inconvenience and discomfort associated with 
longer delivery methods, such as wearing a patch, is eliminated. The 
ability to achieve bacteriocidal effect within the skin (i.e., depth) is 
also advantageous due to the fact that common bacteria contaminants exist 
within the skin and are not always effected by non-iontophoretic delivery 
methods. 
A variety of bacteriocides can be used to practice the present invention. 
Suitable bacteriocides include known anesthetics. Anesthetics that have 
antimicrobial properties are preferred bacteriocides for use in practicing 
the invention. Procaine and lidocaine are two anesthetics that have both 
antimicrobial and anesthetic properties. 
Bacteriocides also include iodine compounds such as solutions of free 
Iodine (e.g., iodide in water, ethyl alcohol, and the like), iodophors, 
quarternary ammonium compounds such as Benzalkonium chloride and 
cetyltrimethyl ammonium bromide, chlorhexidine gluconate, and acetyl 
salicylic acid (i.e., aspirin). 
Preferred characteristics of bacteriocides for iontophoretic delivery 
include proper ionic form, minimal toxicity to the patient, minimal 
irritation to the patient, ease of skin penetration (e.g., molecular 
weight), good water solubility, quick action, and broad spectrum. 
Silver is also a known bacteriocide that can be used in the present 
invention. The bacteriocidal properties of silver have been known for some 
time. Free silver ions, as are used in iontophoretic delivery, due to 
their small size, can penetrate virtually any structure that has an 
aqueous component. Since silver ions are continuously released from the 
electrode (e.g., anode) the amount of silver delivered into the skin and 
beneath the skin is generally in excess of that necessary for obtaining a 
bacteriocidal effective amount. Even though excess silver may be 
delivered, silver is only minimally toxic and the amount typically 
delivered by iontophoresis is far below any amount necessary to produce a 
detectable body burden. 
Although the delivery of a bacteriocide to the locale from which a blood 
sample is to be obtained is responsible for obtaining essentially 
contaminant free blood samples, other substances can be iontophoretically 
delivered along with the bacteriocide. For example, if the bacteriocide is 
not an anesthetic, anesthetic can be iontophoretically delivered with the 
bacteriocide to help alleviate any pain or discomfort that may be 
associated with obtaining blood. Suitable anesthetics include benzocaine, 
procaine, lidocaine, ropivacaine, etidocaine, bupivacaine, tetracaine, 
prilocaine, the salt forms of anesthetics, and mixtures thereof. Likewise, 
known enhancers for increasing penetration can be delivered along with the 
bacteriocide, anesthetic, or both. Enhancer compounds known for promoting 
diffusion of substances through the skin include dimethly lauramide, 
1-dodecylazocycloheptan-2-one, glycerol dimethyl ketal, isopropyl 
myristate, and N,N-diethyl-toluamide. J. Pharm. Sci., 71:1211 (1982). 
Drug modification (e.g., anesthetics), if necessary for ionotophoretic 
delivery, is guided by well-known procedures. For example, to deliver a 
positively charged drug, the chloride or hydrochloride form of the drug 
can be made and placed in the iontophoretic device reservoir for delivery. 
General texts in the field include Remington's Pharmaceutical Sciences, 
Ed. Arthur Osol, 16th ed., 1980, Mack Publishing Co., Easton, Pa. 
Typically, the basic (OH.sup.- or amine) or acidic (H.sup.+) form of the 
drug is made, depending on whether the anionic (negative charged ion) or 
cationic (positive charged ion) form of the drug is to be delivered. 
Common modifications include modification to a halide salt form. For 
example, to deliver a positively charged drug , the chloride or 
hydrochloride form of the drug is made and placed in the iontophoretic 
device reservoir for delivery. Likewise, the composition is typically 
dissolved in a suitable solvent to obtain the ionic form for iontophoretic 
delivery. Suitable solvents include polar liquids such as water, 
glycerine, and lower alkyl alcohols such as methyl alcohol, ethyl alcohol, 
and branched alcohols such as isopropyl alcohol. 
In addition to iontophoretic delivery, anesthetics, enhancers, and the 
like, can be administered topically. Subsequent practice of the invention 
can then be employed. 
After the bacteriocide has been delivered to the surface and into the skin, 
a sample of blood can be withdrawn. Since the locale from which the blood 
sample to be obtained has been treated with a bacteriocide, essentially no 
bacterial contaminants from the skin (e.g., on the surface or within) will 
enter the withdrawn blood. This is particularly advantageous since most 
sterile techniques involving blood samples introduce contaminants from or 
within the skin into the obtained blood sample. It is the introduction of 
contaminants at this point in most blood sample collection techniques that 
is responsible for the contamination problems providing the high number of 
false positives. Typical normal flora of skin which are common 
contaminants responsible for false positive blood cultures include 
Staphylococcus aureus and Staphylococcus epidermidis. H. L. Moffet, 
"Clinical Microbiology, second edition", (J. B. Lippincott Company, 
Phila., Pa., 1980). However, all gram-negative and gram-positive bacteria 
are generally susceptible to the bacteriocidal effects of silver. This is 
also advantageous since not all antibiotics and bacteriocides are 
effective for the same range of bacteria. In addition, since the typical 
blood collection means involves such a small invasion into the skin, the 
iontophoretically delivered silver is especially effective. There is no 
need for the silver to be effective over a wide area of skin. 
By practicing the present invention, the iontophoretic delivery of a 
bacteriocidal effect amount of a bacteriocide substantially eliminates the 
contaminants responsible for providing the large numbers of false 
positives. 
Although the invention has been described with respect to specific 
modifications, the details thereof are not to be construed as limitations, 
for it will be apparent that various equivalents, changes and 
modifications may be resorted to without departing from the spirit and 
scope thereof, and it is understood that such equivalent embodiments are 
to be included therein.