Agricultural Uses of Antibiotics - ACS Publications - American

8

Significance of Antibiotics in Foods and Feeds

Downloaded by UNIV OF CALIFORNIA SANTA CRUZ on February 14, 2018 | https://pubs.acs.org Publication Date: September 18, 1986 | doi: 10.1021/bk-1986-0320.ch008

Khem M. Shahani and Paul J. Whalen Department of Food Science and Technology, University of Nebraska, Lincoln, NE 68583-0919

The use of a n t i b i o t i c s in livestock production for increased feed e f f i c i e n c y i s widespread. Such use may i n d i r e c t l y access human food i n the form of residuals i n products such as meat and milk. For years, scient i s t s and health o f f i c i a l s have warned of the risk of developing resistant pathogens from feeding a n t i b i o t i c s to livestock. Recently, this concern was fueled by a f a t a l case of salmonellosis caused by an a n t i b i o t i c resistant s t r a i n linked to meat. F a i l u r e to withhold milk produced after treating mastitic or otherwise diseased animals i s the primary cause of a n t i b i o t i c s i n milk. L a c t i c cultures produce inherent a n t i b i o t i c s active against a wide range of pathogenic and nonpathogenic bacteria. The benefits of the naturally occurring a n t i b i o t i c s produced i n fermented milk products are being investigated for use i n treating E. c o l i mediated diarrhea and Salmonella/Shig e l l a dysentery i n children. Although the economic advantages of incorporating a n t i b i o t i c s i n animal feed for livestock production are massive, the r i s k to the consumer must be weighed against such advantages.

The advent of a n t i b i o t i c s began a new era i n the treatment of human and animal disease. I n i t i a l l y , a n t i b i o t i c s were used i n a therapeutic mode only. However, i n the early 1950 s, i t was discovered that the residual mash from chlortetracycline production produced a growth promoting effect on chicks which was l a t e r attributed to low levels of the a n t i b i o t i c present i n the mash. Use of a n t i b i o t i c s i n feeds for animal production has grown to account for about half of over 35 m i l l i o n lbs produced annually i n the U.S. (1). Concern that t h i s extensive use may be compromising human therapeutic use i s mounting due to increasing prevalence of multiply a n t i b i o t i c resistant i n t e s t i n a l bacteria, not only i n the f l o r a of the treated animal, but i n the producer personnel as well. Of p r i n c i p a l concern are the complications presented by pathogens such as salmonella whose DNA containing plasmids (R factor) allow acquisition of mul0097-6156/ 86/ 0320-0088506.00/ 0 © 1986 American Chemical Society

Moats; Agricultural Uses of Antibiotics ACS Symposium Series; American Chemical Society: Washington, DC, 1986.

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Antibiotics in Foods and Feeds

t i p l e resistance and present serious, p o t e n t i a l l y f a t a l , upon transmission to humans.

illness


A n t i b i o t i c s i n Foods and Feeds A n t i b i o t i c residuals i n food products are considered additives by the FDA. Therefore, such products are considered adulterated and r e s t r i c t e d from interstate commerce. In addition, widespread use of a n t i b i o t i c s for food production may pose the r i s k of toxic or a l l e r g i c reactions i n sensitized individuals. Cultures employed i n fermented dairy products such as cheese or yogurt are extremely susceptible to low levels of a n t i b i o t i c s i n the milk supply where production schedules may be thrown off and product losses incurred due to the presence of a n t i b i o t i c s . A l t e r n a t i v e l y , some l a c t i c cultures synthesize natural a n t i b a c t e r i a l , a n t i b i o t i c - l i k e compounds active against a wide range of pathogenic and nonpathogenic bact e r i a . In view of some adverse effects of a n t i b i o t i c feeding, use of these probiotics i s being promoted. Several countries other than the U.S. permit the use of n i s i n i n dairy products as a bacteriocin which i s not therapeutically employed i n man or animals. A n t i b i o t i c resistant microorganisms. Livestock production employs a n t i b i o t i c s i n 3 basic manners (2): 1) Therapeutic - treatment of disease and i n f e c t i o n 2) Prophylaxis - disease prevention i n healthy animals 3) Growth promotion - continual subtherapeutic or low doses of a n t i b i o t i c s i n normal, healthy animals for improved production (growth rate and/or feed e f f i c i e n c y ) . Therapeutic levels of a n t i b i o t i c s range from 200 - 500 g/ton while prophylactic applications range from 50 - 200 g/ton and subtherapeutic levels i n feed range from 1 - 5 0 g/ton for poultry, swine and calves (3^). I t i s the long terra or continual incorporation of a n t i b i o t i c s i n feeds which concerns many s c i e n t i s t s i n that many of the a n t i b i o t i c s used for production purposes are also used for therapy i n man. As w i l l be discussed, the resistant organisms which result from a n t i b i o t i c s i n feeds can subvert, potenti a l l y , therpeutic application of these drugs should the resistant organisms present a pathogenic s i t u a t i o n i n man. The presence of a n t i b i o t i c resistant i n t e s t i n a l organisms res u l t i n g from the use of a n t i b i o t i c s i n feeds i s well established (4_, 5_, 6). Wanatabe (7) reported on the t r a n s f e r a b i l i t y of this t r a i t and Anderson and Lewis (8) showed the transfer of a n t i b i o t i c resistance between species involving Salmonella typhimurium. Siegel et a l . (5) showed the effect of a n t i b i o t i c feeds on the number of a n t i b i o t i c resistant IS. c o l i i n swine, poultry and c a t t l e as compared to range c a t t l e . As shown i n Table I, extremely high percentiles of resistant cultures were found i n the animals on feed versus very low levels i n the range c a t t l e . The spread of these resistant f e c a l f l o r a to man has been demonstrated by Levy et a l . (6). In this study, the farm personnel acquired a s i g n i f i c a n t l y higher population of tetracycline resistant coliforms (mainly 15. c o l i ) as compared to neighboring participants not employing a n t i b i o t i c supplemented feed. Multiple resistance i n the bacteria


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Table I, E f f e c t Consuming of A n t i b i o t i c Supplemented Feeds on the Incidence of Resistant E. c o l i % Resistant


Antibacterials Oxytetracycline Dihydrostreptomycin Ampicillin Neomycin Sulfamerazine

Illinois Swine 89.8 93.2 52.5 20.5 82.9

Illinois Poultry 59 72 17 0 21

Illinois Beef 49.1 50.0 13.2 12.3 29.2

Montana Range Cattle* 0 0.6 1.3 0 0.6

*Range c a t t l e , minimally exposed to a n t i b i o t i c s , served as the control. was noted for both human and animal subjects and linked with the tetracycline plasmid. The animal to human link has been reported i n a number of studies. Holmberg et a l . (9) summarized 52 outbreaks of salmonella investigated by the Centers for Disease Control from 1971 to 1983 of which food animals were linked with 69% of the outbreaks involving a n t i b i o t i c resistant salmonella. For 38 outbreaks of confirmed mode or source (Table I I ) , multiply resistant salmonella were involved i n 33% of the community based outbreaks, 40% of the nosocomial, and 75% of the outbreaks i n volving both community and hospital. In addition, i t has been estimated that each culture-documented case among human beings may represent as many as 100 undocumented cases (10). Agency part i c i p a t i o n for these cases was made at the request of the l o c a l health o f f i c i a l s and therefore the survey was not random. However, the resistant strains displayed a f a t a l i t y rate 21 times that of a n t i b i o t i c sensitive strains. O'Brien et a l . (10) found that characterization of plasmid DNA from a n t i b i o t i c resistant salmonella suggests extensive commingling of human and animal bacteria. Table I I . Outbreaks of Salmonellosis Between 1971 and 1983 Reported by CDC

Source Food Animals or Products Food Services Other Sources Person to Person

Number of Outbreaks* Community Nosocomial Both 7/12 3/4 1/2 1/10 0/2 0

0/1 1/2 2/5

0 0 0

Resistant Strains 61% 9% 25% 40% 39.5%

Mean % Resistant Strains 33% 40% 75% Adapted from: Holmberg et a l . (9) *Resistant s t r a i n s / t o t a l outbreak for cases of s p e c i f i c source or mode of transmission.

Evidence for the demonstration of the link of subtherapeutic use of a n t i b i o t i c s i n animal feeds to severe disease i n humans was



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proposed i n the highly publicized Minnesota outbreak involving a multiply resistant Salmonella nevport (11). The provision of evidence linking the subtherapeutic use of a n t i b i o t i c s i n feeds to human disease was not conclusive and the proof of o r i g i n as well as meat samples confirming the source for the j>« newport were not clearly established. However, this study c l e a r l y points out the risks involved with establishing multiply resistant enteric pathogens which access human food products. This study combines the l i b e r a l manner i n which a n t i b i o t i c s are used (prescribed or not) by the general public for cold-type symptoms with the onset of a severe disease state i n an otherwise benign and common i l l n e s s . Of the 18 cases investigated, 11 were hospital i z e d f o r an average of 8 days and 10 of these were taking a n t i b i o t i c s prior to the onset of salmonellosis. For the single f a t a l i t y among these cases, the multiply resistant salmonella compromised a n t i b i o t i c therapy where a systemic salmonella i n f e c t i o n occurred. Salmonella i s considered an inherent defect i n raw meats and therefore i s not considered an adulterant since the ultimate use by the comsumer involves cooking which destroys the organism. Concern that salmonella and other common food borne pathogens may be presenting an increased r i s k to human health v i a a n t i b i o t i c resistance prompted contracted studies recommended by the National Research Council i n 1980. Results of these studies (12) showed widespread multiply resistant Salmonella, Campylobacter, Staphylococcus species and other pathogens among livestock on farms, i n slaughter houses and on the meat i n the U.S. Their transmission to man appears equally evident. Whether the organisms are more virulent has not been shown but certainly they have an advantage when a n t i b i o t i c s are employed to which they are resistant. As has been discussed, the use of a n t i b i o t i c s selects f o r resistant organisms i n the intestine and while these organisms may not be pathogenic ( i . e . - IS. c o l i ) they act as reservoirs of resistant plasmids which can be transferred to pathogenic or nonpathogenic organisms a l i k e . Prior to the a n t i b i o t i c era, was a n t i b i o t i c resistance as prevalent? Some l i g h t has been shed on this question by the work of Hughes and Datta (13). These authors studied the Murray c o l l e c t i o n of Enterobacteriaceae strains collected from 1917 to 1954. They tested 692 strains from 433 i s o l a t e s of which almost a l l were from human infections. Nineteen percent of the strains contained conjugative plasmids but none of the plasmids showed a n t i b i o t i c resistance. This work strongly indicates that the mass emergence of resistant strains i s a product of the a n t i b i o t i c era. Residual a n t i b i o t i c s . With the widespread use of a n t i b i o t i c s i n feeds the occurrence of residuals i n milk, meat and eggs becomes inevitable. These residuals result primarily from f a i l u r e by the producer to adhere to adequate withdrawal periods following the use of the a n t i b i o t i c s . In a review by Katz C3), residual a n t i b i o t i c s were found i n a l l animal species marketed i n 1976 - 1978.


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The lowest incidence of v i o l a t i v e residuals were found i n poultry and c a t t l e , with swine and calves having the highest. A n t i b i o t i c s i n milk result primarily from f a i l u r e to withhold milk from the market after therapeutic treatment of mastitic or otherwise diseased animals. The exposure to a n t i b i o t i c residuals i n food products i s an uncontrolled and involuntary s i t u a t i o n . Ingestion of these admittedly low dose levels has been of concern due to potential for s e n s i t i z a t i o n and/or a l l e r g i c reaction to the a n t i b i o t i c (14). About 10% of the general population exhibit an adverse reaction to p e n i c i l l i n (15). The p o s s i b i l i t y of primary s e n s i t i z a t i o n to a n t i b i o t i c s v i a food products, s p e c i f i c a l l y from p e n i c i l l i n i n milk, was e s s e n t i a l l y ruled out by Dewdney and Edwards (16). Their conclusion rests on the improbability of the low levels encountered i n milk (0.01 microgram/ml) as being capable of s e n s i t i z i n g an i n d i v i d u a l . However, i n view of evidence that low dose immunization can favor antibody production (17), these residual levels could be capable of s e n s i t i z a t i o n (30. Upon s e n s i t i z a t i o n the dose required to e l i c i t an a l l e r g i c reaction i s highly dependent upon the individual but may be as l i t t l e as 40 IU (0.024 mg) i n a highly sensitized person. Dewdney and Edwards (16) c i t e the paucity of cases i n the l i t e r a t u r e to warrant the concern given to p e n i c i l l i n residues i n milk and question the v a l i d i t y of those that are. However, given the widespread use and misuse of p e n i c i l l i n and the potential for reaction i n the above estimated 10% of the population, continued concern appears warranted. A n t i b i o t i c s i n milk can affect dramatically the production of fermented dairy products such as cheese, yogurt, buttermilk and sour cream. Routine application of a n t i b i o t i c test k i t s such as the Delvo k i t are required to avoid major losses on the l i n e . Many of the organisms employed are extremely sensitive to a n t i b i o t i c residuals i n the milk. As shown i n Table I I I , as l i t t l e as 0.05 to 1.0 IU/ml of p e n i c i l l i n and 0.05 to 10.0 microgram/ml of aureomycin inhibited the growth of 19 cheese starter cultures (18). Lower levels are capable of affecting the flavor and texture properties of the product (14, 19) as well as promoting the growth of undesirable a n t i b i o t i c resistant coliforms (14, 20). Benefits of A n t i b i o t i c s Modern methods of livestock production are intensive and the environmental conditions stress the animals. The use of a n t i b i o t i c s promotes growth and protects the animals from otherwise certain i n f e c t i o n under these conditions. A n t i b i o t i c - l i k e compounds formed i n l a c t i c acid fermentations prevent p r o l i f e r a t i o n of spoilage and pathogenic microorganisms and increase the shelf l i f e of the products. N i s i n i s a antimicrobial produced by a l a c t i c acid bacterium and i s used i n some countries as a food preservative. Some l a c t i c acid bacteria are capable of favorably influencing the f e c a l f l o r a i n man and animals. Livestock production. The growth promoting attributes of a n t i b i o t i c s i n feeds reside i n their a n t i b a c t e r i a l a c t i v i t y i n the


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Table I I I .

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Minimum Inhibitory Levels of P e n i c i l l i n and Aureomycin for Common Dairy Starter Cultures


1

Aureomycin Penicillin yg/ml U/ml Cultures 1.0 0.05 Lactobacillus l a c t i s A 1.0 0.05 Lactobacillus l a c t i s B 3.0 0.05 Lactobacillus l a c t i s VI04 0.5 0.30 Lactobacillus l a c t i s 431 1.0 0.30 Lactobacillus l a c t i s kw 0.3 0.05 Lactobacillus l a c t i s V109 1.0 0.05 Lactobacillus l a c t i s , myc 3.0 0.10 Lactobacillus bulgaricus 488 5.0 0.10 Lactobacillus bulgaricus 444 3.0 0.30 Lactobacillus bulgaricus R 2.0 0.20 Lactobacillus bulgaricus V71 0.3 0.05 Lactobacillus bulgaricus VI2 10.0 1.00 S and R 0.3 0.05 Streptococcus thermophilus H 0.3 0.05 Streptococcus thermophilus T 0.05 0.05 Streptococcus l a c t i s 9 0.05 0.05 Lactobacillus casei 0.2 0.10 Streptococcus durans 0.05 0.05 Micrococcus 8406 •••Adapted from: Shahani and Harper (18). ^Commercial Mixed Culture Containing L. l a c t i s and L. bulgaricus. 2

i n t e s t i n e . This i s corroborated by the lack of improvement i n growth of germ-free chicks fed a n t i b i o t i c supplemented feed (21). The improvement i n growth i s probably a combined effect of the a n t i b i o t i c on the f l o r a and the small i n t e s t i n e . A n t i b i o t i c fed chicks showed h i s t o l o g i c a l changes i n the intestine similar to those for germ-free chicks as well as shorter and thinner walled i n t e s t i n e s . Nutrient uptake i s believed to be enhanced by these changes (3). In ruminants, growth promotion i s due to increased propionate producing bacteria by selective i n h i b i t i o n of competing f l o r a , decreased microbial protein, decreased rumen solids and d i l u t i o n rate and increased metabolizability (not d i g e s t i b i l i t y ) (2). Other contributing factors may be suppression of mild but unrecognized infections, reduced microbial destruction of essent i a l nutrients, reduced microbial toxins and synthesis of v i t a mins or other growth promoting factors which become available subsequently to the animal. Naturally occurring a n t i b i o t i c s i n foods. L a c t i c acid producing bacteria have been selected h i s t o r i c a l l y for food preservation i n fermented foods such as sausage, cheese, yogurt, sauerkraut etc. Their p r i n c i p l e mode of a n t i b i o s i s i s through the rapid production of organic acid (mainly l a c t i c ) and the associated lowering of the pH. Other metabolites such as hydrogen peroxide also havebeen recognized as factors i n the prevention of spoilage of f e r mented products. The consistent use of high numbers of l a c t i c acid bacteria i n fermented meats provides for a rapid fermentation which precludes the p r o l i f e r a t i o n of pathogens such as


94


Staphylococcus aureus, Salmonella spp. and Clostridium botulinum (22). In the case of the l a t t e r , the combination of l a c t i c s t a r t e r with either sucrose or dextrose has proven e f f e c t i v e i n preventing toxin production even without n i t r i t e C23, 240 • Table IV i l l u strates the i n h i b i t o r y effect of l a c t i c cultures on the growth and production of enterotoxin by staphylococci i n dry sausage (25).


Table IV.

I n h i b i t i o n of Pathogenic Staphylococci L a c t i c Cultures i n Sausage

Storage, 3 da Sausage Toxin Log CFU pH formulation + 8.84 5.9 Without l a c t i c starter With l a c t i c 6.78 5.6 starter Adapted from: Niskanen and Nurmi (25)

-

by

Storage, 7 da pH Toxin CFU

Log

8.88

5.7

+

7.53

5.3

-

The provision of l a c t o b a c i l l i as therapy for acute diarrhea brought on by enteropathogenic IS. c o l i (EEC) has been demonstrated i n v i t r o and i n vivo (26). G i l l i l a n d and Speck (27) found a high degree of i n h i b i t i o n of Salmonella typhimurium, Staphylococcus aureus and EEC when grown i n associative culture with Lactobacillus acidophilus (Table V); they attributed the i n h i b i tory action to l a c t i c acid, hydrogen peroxide and other i n h i b i t o r y compounds. The i n h i b i t o r y compounds have been studied further and isolated (28 -_38). They are l i s t e d i n Table VI. The product i o n of these a n t i b i o t i c s generally required s p e c i f i c media and growth conditions. Recent work i n our laboratory investigated the effect of L. acidophilus on Staphylococcus aureus under yogurt production conditons (39). We found the i n h i b i t i o n due to the acid. Hydrogen peroxide production did not account for the t o t a l i n h i b i t i o n observed i n the yogurt. Table V.

Test Culture

s. aureus s.

typhimurium

E. c o l i

Adapted from:

I n h i b i t i o n of Pathogens by L. acidophilus i n Associative Culture Treatment

Pathogen (CFU/ml), 1.5 X T o 2.7 X 1.7 X 10 c 2.3 X 3.3 X 4.3 X 10 7

Control L. acidophilus Control L. acidophilus Control L. acidophilus G i l l i l a n d and Speck

Inhibition (%) 98.2

6

86.5 87.0

6

(27)

Shahani and coworkers (29, ^4, 40, 41_) studied a c i d o p h i l i n and bulgarican from s p e c i f i c strains of L. acidophilus and L. bulgaricus, respectively. These compounds were of low molecular weight and demonstrated a wide range of a c t i v i t y against gram negative and gram positive organisms. Table VII shows the results


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Table VI. Natural A n t i b i o t i c s Produced by L a c t i c Cultures

Culture Lactobacillus acidophilus

Lactobacillus brevis

Compound Acidolin Acidophilin Lactocidin Lactobacillin (H 0 ) Lactobrevin Bulgarican Lactolin Diplococcin Nisin


2

Lactobacillus Lactobacillus Streptococcus Streptococcus

Table VII.

bulgaricus plantarum cremoris lactis

Reference (28) (29) (30)

2

(31-32) (33) (34) (35) (36) (37-38)

In V i t r o A n t i b a c t e r i a l Spectrum of A c i d o p h i l i n

1

2

IC (ug/ml) Strain Test Organism 30 ATCC 6633 Bacillus subtilis 29 Difco 902072 B a c i l l u s cereus 43 ATCC 7954 B a c i l l u s stearothermophilus 45 ATCC 8043 Streptococcus f a e c a l i s 42 ATCC 4532 Streptococcus f a e c a l i s var. liquefaciens 30 NUC Streptococcus l a c t i s 6 40 LY-3 France 7 Lactobacillus l a c t i s 42 ATCC 7469 Lactobacillus casei 8 60 ATCC 8014 Lactobacillus plantarum 9 59 ATCC 7830 Lactobacillus leichmannii 10 30 ATCC 9341 11 Sarcina lutea 29 NU 12 Serratia marcescens 32 NU Proteus vulgaris 13 32 NU 14 Escherchia c o l i 30 ATCC 167 15 Salmonella typhosa 30 ATCC 417 16 Salmonella schottmulleri 30 ATCC 934 17 Shigella dysenteriae NU (coagulase + ve) 50 18 Staphylococcus aureus 60 Phage 80/81 19 Staphylococcus aureus 60 ATCC 9997 20 K l e b s i e l l a pneumoniae 30 ATCC 9459 21 Vibrio comma Adapted from: K i l a r a and Shahani (41). 2lC - concentration i n h i b i t i n g 50% ofgrowth. 5 0

No. 1 2 3 4 5

x

5 0

of i n v i t r o a n t i b a c t e r i a l a c t i v i t y f o r a c i d o p h i l i n against pathogenie and nonpathogenic organisms (41). Beyond the potential product s t a b i l i t y against pathogens imparted by these compounds, the possible health benefits to the consumer have not been shown. N i s i n i s an antimicrobial elaborated by Streptococcus l a c t i s N. Due to the fact that n i s i n i s not used f o r human or animal therapy or as a feed additive and growth promotor, i t s use i n food i s per-



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mitted i n over 35 countries (42). L i t t l e or no d e f i n i t i v e i n f o r mation i s available concerning the probability of the development of cross-resistance between n i s i n and other medically important a n t i b i o t i c s . However, use of n i s i n i s not permitted for food i n the U.S. or Canada. N i s i n i s not inhibitory to yeasts, fungi, or gram negative organisms but i s active against several gram positive streptococci, l a c t o b a c i l l i , C l o s t r i d i a , staphylococci and b a c i l l i (43, 44). For successful application of n i s i n to a food product, Hurst (42) suggests that the food be a c i d i c and that the spoilage organims of concern be gram positive. N i s i n was f i r s t used e f f e c t i v e l y to prevent gas defects caused by Clostridium butyricum i n Swiss cheese (45). The use of n i s i n as a potential adjunct to or replacement of n i t r i t e i n simulated hams was suggested by Rayman et a l . (46). These investigators found that due to an additive e f f e c t , the n i t r i t e l e v e l could be reduced from 150 ppm to 40 ppm while retaining color s t a b i l i t y and preservation q u a l i t i e s . However, they reported also the i n s t a b i l i t y of the n i s i n after storage at low temperatures followed by temperature abuse. The higher levels of n i s i n needed to compensate for these factors may make this use uneconomical according to Hurst (42). Natamycin (Pimaricin) has been approved for use on the surface of cheese and cheese s l i c e s for mold i n h i b i t i o n (47). Shahani (48) found that natamycin treated cheeses inoculated with toxigenic molds e f f e c t i v e l y prolonged the shelf l i f e . Summary The widespread use of a n t i b i o t i c s i n current livestock production methods offers clear cut advantages i n terms of growth and e f f i ciency. However, i n view of the increased incidence of multiple a n t i b i o t i c resistant organisms i n the food products, the risks imparted by resistant food borne pathogens i s of concern to human health. The routes of transfer are varied and may result from routine farm contact with animals and feed, direct transfer from animal to man, or be as complex as transfer from manure to plant f l o r a to man or animal. Evidence of this last mentioned route has been presented by Levy (49). The sheer volume of largely unmanaged or untreated f e c a l material generated from livestock production v i r t u a l l y assures transfer to humans. By comparison, human use of a n t i b i o t i c s i s estimated at less than 1% of animal use, with animals producing manure at a rate up to 400 times that of man (1_)• Nonetheless, r e s t r i c t i o n s on the subtherapeutic use of a n t i b i o t i c s i n feeds should be met with an equal scrutiny of human therapeutic abuse. L i b e r a l prescribing of these valuable drugs, largely to prevent secondary b a c t e r i a l infections following v i r a l cold-type infections, i s a useless remedy and serves to exacerbate the human health question concerning infections involving resistant organisms. That resistant pathogens may complicate human therapeutic application i s a fact. These resistant organisms threaten application of a n t i b i o t i c s deemed v i t a l i n human treatment. The course that industry and government set must balance food production objectives with long term public health considerations. More prudent use of a n t i b i o t i c s i n the feed industry



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as well as i n human medicinal practice i s required i n order to e f f e c t i v e l y reserve a n t i b i o t i c s for the treatment of serious microbial disease i n humans. The human microflora can be influenced e f f e c t i v e l y by ingestion of l a c t o b a c i l l i . Work i n our laboratory has shown a severe reduction of coliforms i n the human stool by l a c t o b a c i l l i . These organisms present a highly corapetative environment for salmonella and other pathogens. L a c t o b a c i l l i have a s t a b i l i z i n g effect on the i n t e s t i n a l f l o r a and, i f used with proper consideration, could act to prevent s h i f t s i n the i n t e s t i n a l microflora that favor disease from resistant pathogens. This application could find a role i n c o n t r o l l i n g the buildup of a n t i b i o t i c resistant organisms i n farm personnel who are routinely i n contact with a n t i b i o t i c supplemented feeds. Research on a n t i b i o t i c s which do not produce multiple resistance i s , of course, desirable. N i s i n appears to present just such a situation although i t s applications are narrow. Some feed additives are capable of "curing" multiple resistance i n enterics (50). This area deserves more research and emphasis.

Literature Cited 1.

Levy, S. B. N. Engl. J . Med. 1984,

2.

Armstrong, D. G. In "Antimicrobials and Agriculture"; Woodbine, M., Ed.; Butterworths: London, 1984; p. 31.

3.

Katz, S. E. In "Antimicrobials i n Foods", Brannen, A. L. and Davidson, P. M., Eds.; Marcel Dekker, Inc.: New York, 1983; p. 353.

4.

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