WATER MEDICATION WITH ANTIBIOTICS

 

Glen Almond and Kelli Monahan

Department of Farm Animal Health & Resource Management

College of Veterinary Medicine
North Carolina State University

Raleigh, NC 27606

Introduction

 

Injections of antibiotics are used to treat individual pigs affected with bacterial infections. However, with increased numbers of pigs in a facility, labor constraints, and the ability of some pathogens to spread to a high proportion of a herd, producers often use a therapeutic approach for a ‘population’ of pigs. This approach typically involves the oral administration of antibiotics through the drinking water. Water medication offers the distinct advantages of minimizing labor requirements and providing therapy to a large number of animals. Farm personnel commonly prefer to use water medication because of the relative ease of the method compared to using injectable antibiotics. 

At a previous Healthy Hogs Seminar (1998), Dr. Al Scheidt gave an informative presentation on respiratory disease on finishing floors. A list of the water-soluble antibiotics and the significance of extra-label drug use were provided in the conference proceedings. Our presentation and paper are not intended to duplicate the previous presentation; however, a review of the problems associated with water medication is well justified. First, there is increasing consumer and governmental concerns regarding antibiotic resistance problems associated with bacterial pathogens. These concerns currently are focused on the inclusion of antibiotics in feed. Feed-grade antibiotics were banned in some European countries, including Denmark and Sweden. If our pork industry is similarly mandated to eliminate the use of feed-grade antibiotics, then it is likely that we will become increasingly dependent on water medication.

In view of the preceding discussion, the first goal of this presentation is to heighten awareness of the potential problems encountered with water medication. The second goal is to motivate producers (and veterinarians) to improve their water medication methods and to consider the ramifications of indiscriminate antibiotic use.

 

Antibiotics Available for Water Medication

 

Unfortunately, veterinarians and pork producers have a limited number of antibiotics to choose for water medication. Table 1 gives examples of common antibiotics intended for water medication. It cannot be overemphasized that some of the antibiotics are NOT licensed for use in swine.

The use of antibiotics licensed for other animals (usually poultry), diseases other than ones indicated on the label, or at a dose exceeding the label recommendation is either considered extra-label drug use or in some cases, illegal. ALWAYS confer with your veterinarian if you have any questions regarding the indications, dosage and administration, cautions and warnings on the product label. The last things the pork industry needs are antibiotic residue problems and claims that antibiotics were used illegally.

 

Table 1. Examples of antibiotics used for water medication.
This list does not include all brand names. Inclusion in the list does imply endorsement by the authors.

 

Antibiotic

Brand Name Example

Indications

Oxytetracycline

Terramycin-343 Soluble

Powder ̉.

Bacterial enteritis caused by E. coli and Salmonella choleraesuis; Bacterial pneumonia caused by Pasteurella multocida; Leptosporosis caused by Leptospira pomona

Chlortetracycline

Aureomycin Soluble Powder Concentratẻ. 

Bacterial enteritis (scours) (E. coli & Salmonella spp); bacterial pneumonia (Pasteurella spp, Hemophilus spp, Klebsiella spp)

Tetracycline

Tetracycline Soluble Powder̉,

Tetra-324̉.

An aid in the prevention and treatment of bacterial enteritis and bacterial pneumonia in swine. Bacterial enteritis (scours) (E. coli); bacterial pneumonia associated with Pasteurella spp, Hemophilus spp, Klebsiella spp susceptible to tetracycline.

Tiamulin

Denegard Soluble Antibiotic̉

Actinobacillus pleuropneumonia (APP) (10.5 mg/lb), swine dysentery (3.5 mg/lb)

Gentocin

Garacin̉

E. coli in weanling swine, swine dysentery

Lincomycin

Lincomix Soluble Powder̉

Treatment of swine dysentery.

Neomycin

Neo 128̉, Neo 325̉, Neovet 325̉

Treatment and control of colibacillois caused by E. coli susceptible to neomycin sulfate.

Spectomycin

Spectam Water Solublẻ

Labeled only for poultry The oral solution (Spectam Scour-Halt̉) is intended for E. coli scours

Sulfamethazine

Sulmet̉

Porcine colibacillosis and bacterial pneumonia (Pasteurella spp)

Lincomycin/

Spectomycin

L-S 50 Soluble Powder̉

Labeled only for poultry

Chlorotetracycline/sulfamethazine

Aureomycin Sulmet Soluble Powder̉

Bacterial enteritis; aid in the maintenance of weight gains in the presence of atrophic rhinitis; reduce the incidence of cervical abscesses.

Tylosin

Tylan Solublẻ

Treatment and control of swine dysentery or other pathogens sensitive to tylosin.

Penicillin G Potassium

 

Labeled for turkeys

Compendium of Veterinary Products, 5th Edition, 1999.

 

After examining Table 1, it should be evident that there are relatively few antibiotics available for use in pigs, and that some of the antibiotics are used to treat certain types of bacteria that are not included on the “indications” section of the product label. For example, it is not unusual to use water medication for porcine respiratory disease complex (PRDC) in finishing hogs. One of the major organisms involved in the PRDC is Mycoplasma hyopneumoniae; however, the water medications are not approved for the control or treatment of M. hyopneumoniae. According to Ross (Diseases of Swine, 1999), tetracyclines, tiamulin, tiamulin+chlortetracycline, or tiamulin+oxytetracycline may be beneficial for the control of M. hyopneumoniae, but none of these antibiotics are labeled for M. hyopneumoniae. Therefore, the limited number of antibiotics available for water medication, and the questionable legality of using some of the antibiotics compound our dilemma of treating large numbers of pigs.

 

Bioavailability and Absorption

 

Absorption of oral antibiotics is highly variable. Some antibiotics, such as tiamulin, (Denegard̉) are readily absorbed by the gut and significant blood concentrations are achieved within hours (Plumb, 1999). In contrast, spectinomycin and neomycin are poorly absorbed. The fact that some of the antibiotics are poorly absorbed should not be considered as a negative attribute. As shown in Table 1, the poorly absorbed antibiotics typically are labeled for the control or treatment of enteric pathogens, which cause diarrhea. The readily absorbed antibiotics are intended to treat systemic or respiratory pathogens. The important concept is that the antibiotics were developed for specific disease conditions. 

The tetracyclines (oxytetracycline, tetracycline and chlortetracycline) are widely used for water medication; however, the bioavailability of tetracyclines is low following oral dosing compared to intravenous injections of grow/finish pigs (Mevius et al., 1986; Nielsen & Gyrd-Hansen, 1996). Figure 1 shows the plasma concentrations of oxytetracycline after intravenous and oral administration to pigs (approximately 70 lb BW). It should not be surprising that intravenous or intramuscular injections provide more rapid increases and greater blood levels of antibiotics than water medication. Thus, the use of water medications cannot be expected to achieve the same therapeutic success as injectable antibiotics.

Figure 1. Plasma concentrations of oxytetracycline after intravenous (IV) (10 mg/kg BW) and oral (PO) (45 mg/kg BW) administration to non-fed and fed pigs. Note that the Y axis (concentration) is a logarithmic scale. (Adapted from Nielson and Gyrd-Hansen, 1996).

 

Other factors also impair absorption of most antibiotics used for water medication. The presence of feed in the gastro-intestinal tract interferes with oral absorption of some antibiotics. This may be considered as a positive attribute of water medication, ie, the healthy pigs consuming “normal” quantities of feed require less antibiotics and antibiotic absorption is irrelevant. In other words, if a pig is not sick, one may assume that the antibiotics are not really necessary and who cares if absorption is impaired by the presence of feed in the gut. Unfortunately, pigs in the acute phase of an infection would benefit from antibiotic therapy; however, the feed ingested prior to the onset of infection may interfere with antibiotic absorption, thereby allowing the bacteria to replicate.

To evaluate the bioavailability and absorption of antibiotics in water, previous investigations were conducted with few animals under controlled conditions. These conditions do not take into account potential sources of variation, which result from housing pigs in commercial facilities.

 

Water Consumption and Delivery Systems

 

One of the first signs of illness is the failure of a pig to eat. In cases of respiratory disease, it also is common to observe that affected animals are reluctant to drink. This failure to drink obviously will interfere with the intake of antibiotics in the water. In contrast, a sudden increase in water consumption occurs in pigs approximately one day before the onset of diarrhea (Anonymous, Pig International 29:17-20, 1999). Without the ability to monitor daily water use, any change in water consumption typically is overlooked and water medication is initiated after the onset of clinical signs. These comments regarding increased or decreased water intake essentially are mute points, as water disappearance is rarely monitored in nursery or finishing facilities.  

                In previous Healthy Hogs Seminars and the NC Pork Report, we emphasized the potential shortcomings of previous estimates of the water requirements of pigs. Quite often, water disappearance (water use) is erroneously equated to water intake. Table 2 provides the “best guess” estimates of water requirements.

 

Table 2. Water requirements of pigs. Values were derived from previous studies, which used thermoneutral environments. Most values reflect water use (disappearance). European countries use the ratio of water:feed, which appears to provide a better estimate of water requirements.

 

Class of Pig

Liters/pig/day

Gallons/pig/day

Nursery

(up to 60 lbs BW)

2.8

(2.5-3.0 L/kg feed consumed)

0.7

(0.3 gal/lb feed consumed)

Grower

(60 -100 lbs BW)

8-12

(2.5-3.0 L/kg feed consumed)

2-3

(0.3 gal/lb feed consumed)

Finisher

(100 - 250 lbs BW)

12-20

(2.5-3.0 L/kg feed consumed)

3-5

(0.3 gal/lb feed consumed)

 

                Maintaining reasonable records of water use in finishing (or nursery) barns facilitates efforts to provide antibiotics through the water. The use of water medications is based on the appropriate dilution of concentrated antibiotic powders. Fortunately, water medicators or proportioners reduce, but not eliminate, potential errors in diluting the antibiotics. However, the medicators/proportioners fail to account for the tremendous variation in flow rates of the drinkers in or between pens and rooms.

                Figure 2 illustrates the potential loss in water delivery rate down the length of a barn. Based on the assumption that similar losses occur in finishing facilities in North Carolina, one must suspect that any attempts to provide medicated water will have mixed results. The diminished delivery rates in certain pens may be interpreted as suboptimal delivery of antibiotics. The pigs at the front end of the barn should receive sufficient medicated water to conform to the manufacturer’s recommendations.

Figure 2. Loss of water delivery rate down the length of a barn (Brooks and Carpenter, 1990).

 

With assistance from corporate partners, we conducted a one-year study, which included an assessment of water use (disappearance) in finishing barns and nursery rooms (Figure 3). Two types of drinkers were compared and representative weekly water disappearance is shown in the figures. It should be noted that there was obvious variation in the weekly water use by both drinker types. With this type of variation, any prediction of water use or consumption would be difficult. Therefore, it also would be difficult to prepare the appropriate concentration of stock solution for antibiotics intended for water medication.

Figure 3. Weekly water disappearance in a representative finishing floor (top figure) and nursery room. The initial stocking and subsequent sorting/movement of animals clearly is evident by the change in water disappearance. The symbols represent two types of drinkers.

 

One of the interesting, yet troublesome results from our water delivery studies was the difference in flow rates by the two drinker systems. As shown in Figure 4, water flow rates were consistent between Drinkers Type A and over time. In contrast, the other drinker type had tremendous variation in flow rates. Which drinker would provide the most reliable delivery of medicated water?

 

Figure 4. Variation in flow rates from two types of water drinkers. The upper figure illustrates flow rates for 10 drinkers/type. The lower figure shows the change in flow rates over a several month test period.  

 

 These inconsistencies in water delivery create a problem – providing water medication does not guarantee that all pigs or all pens receive antibiotics. A measurement of water disappearance is not equivalent to water (and antibiotic) consumption. Another important concept relates to the wastewater produced by water spillage while pigs attempt to drink. What happens to the antibiotics in the water? What proportion of the medicated water do the pigs consume? What is the cost (loss) incurred with the loss of antibiotics in wastewater? If there is variation in flow rates and water disappearance, how much variation is occurring in antibiotic consumption and bioavailability?

 

Miscellaneous Problems

 

In addition to potential problems inherent to the antibiotics and the water delivery systems, problems with water quality may also affect the efficacy of water medication. It is not unusual to note a reddish slime in water filters on commercial farms. Microorganisms that use inorganic ferrous iron produce the slime. Obviously, water filters should remove the slime before it reaches the medicator (that is assuming the filter is changed on a regular basis). However, the slime may also plug drinkers and interfere with flow rates. Other causes of impaired water flow include mineralization of pipes and drinkers in hard water areas, rust from galvanized pipes and the accumulation of other solids from contaminated water. The solid material simply blocks drinker orifices. The impaired flow rates interfere with antibiotic delivery in the water.

Previously, the problems with insufficient or highly variable flow rates were described. Another problem arises when there is excessive water pressure or excessive flow rates. High levels of spillage contribute excessive effluent production and considerable loss of medicated water. If we ignore the fate of wasted antibiotics, ie, antibiotics in wastewater and effluent, there are several groups more than willing to provide answers.

 

Following Instructions

 

The following paragraph is an excerpt from a product label.

 

“The concentration of the drug required must be adequate to compensate for variation in the age of the animals, feed consumption and the environmental temperature and humidity, each of which affects water consumption.”

 

We have no intention of criticizing any particular product – all product labels contain similar instructions; however, to accurately follow these type of instructions may be difficult for some individuals. In the preceding sections, we illustrated the variation noted in water delivery systems. We are aware of the variation, but it is difficult to predict how the various factors will affect water consumption, so that we can provide “the concentration of the drug required to be adequate to compensate for variation”.

Another concern regarding product instructions pertains to literacy. We often assume that our employees can read and understand the instructions. This may be challenging, particularly if English is your second language. Unfortunately, the pharmaceutical companies essentially have no choice on label instructions – the instructions are under the strict influence of governmental agencies.

 

Conclusions

 

The inclusion of antibiotics in feed is a contentious issue in food animal production. The likelihood that antibiotics will continue to be added to feed is debatable; however, oral administration of antibiotics in drinking water will presumably remain a common therapy. In general, the pork industry has few choices for water-soluble antibiotics and it is unlikely that we will gain a plethora of new antibiotics.

The delivery (concentrations, dose) of medication in water typically is based on the assumptions that water intake is similar between pigs and that the same or very similar concentrations of antibiotic are delivered to all pens within a barn. Based on our investigations in commercial pig farms, it is evident that water flow rates vary between different water drinkers and barns. Presumably, considerable variation in antibiotic uptake (and plasma concentrations) occurs when pigs receive medication in water, and the inconsistent flow rates of commonly used water drinkers contributes to this variation.

So – why do rely on water medication for the delivery of antibiotics? How can we reduce our dependency? There are no simple answers to these questions; however, we must strive to improve pig health and minimize infectious diseases without massive medication protocols.      

 

Take-Home Message

 

·         Confirm the diagnosis of the disease and antibiotic sensitivity of the bacterial pathogen. Why use an antibiotic if the bacteria are not sensitive to it?

·         Don’t be afraid to install water meters and monitor water disappearance in your finishing barns. This will provide a reasonable estimate of water use. Adjust your medicator or proportioner and stock solutions accordingly.

·         Make sure the drinkers are providing sufficient, but not excessive, flow rates. Be aware of the variability in flow rates between pens and barns.

·         Be careful of extra-label product use and the legal implications if you intend to use a product that is not approved for use in swine.

If all else fails, READ THE INSTRUCTIONS ON THE PRODUCT LABEL!

 

References

 

Mevius, D.J., Vellenga, L., Breuking, H.J. et al. 1986. Pharmacokinetics and renal clearance of oxytetracycline in piglets following intravenous and oral administration. Vet. Quarterly 8:275-284.

Nielsen, P. and Gyrd-Hansen N. 1996. Bioavailability of oxytetracycline, tetracycline and chlortetracycline after oral administration to fed and fasted pigs. J. Vet. Pharmacol. Therap. 19:305- 311.

Plumb, D.C. 1999. Veterinary Drug Handbook. 3rd Edition. Iowa State University Press: Ames, Iowa.