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4. Study Possibilities
Pages 35-51

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From page 35...
... Study 1 should identify relative contributions of subtherapeutic and therapeutic antimicrobial regimens to the emergence of resistant enteric flora in animals. Studies 2 and 3 are designed to assess the extent to which carriage by humans of bacteria having R factors is associated with meat consumption or occupational exposure to bacteria from animals in abattoirs.
From page 36...
... Within each animal species, individual animals not previously exposed to ant~microbials should be allocated randomly to pens, and the pens should be assigned randomly to treatment groups, each of which contains more than one pen of animals. The number of animals in each pen and the number of pens may differ along the three animal species and should be specified so that the samples are of sufficient size for investigators to detect meaningful differences in the proportions of animals carrying tetracycline-resistant organisms among the various treatment groups.
From page 37...
... These animals should not receive subtherapeutic antimicrobials. A simulated typical course of tetracycline therapy should be administered to the group at a specified time during the feeding period in accordance with accepted veterinary practices for the test species.
From page 38...
... For each stool specimen, the Enterobacteriaceae should be enumerated and serotyped, and the percentage carrying R factors mediating resistance to tetracycline should be ascertained by quantitative culture techniques. Salmonellae shed by each animal should be enumerated and serotyped.
From page 39...
... Investigators should determine the number to be used in accordance with the principles indicated in the study design outlined above. Animals should be observed past the usual marketing time in order to assess the full consequences of antimicrobial withdrawal on the microbial flora.
From page 40...
... Acquisition of 120 400-lb calves at approximately $1.25/lb will cost: 120 x 400 lb x $1.25/lb Feed and Care Costs: 120 x 240 days x $5.00/day Veterinary Supervision (2 h/day) : 2 h x 240 days x $30/h Animal Husbandry: Total Direct Cost = =- $ 60,000 = 144,000 - 14,400 Laboratory Services (based on one specimen/animal every 3 days)
From page 41...
... : 180 days x 2 h x $30/h Animal Husbandry: Total Direct Cost = , approxi = $ 21,600 = 43,200 = 10,800 Laboratory Services (based on one specimen/animaI every 3 days) : 60 specimens/animal x 120 animals x $25/specimen Total Direct Costs Overhead (estimated 50%)
From page 42...
... Feed and Care Costs: 300 chickens x $0.50/day x 100 days Veterinary Supervision (2 h/day) : 100 days x 2 in/day x $30/h Anima1 Husbandry: Total Direc t Cost = $ 4,500 = 15,000 = 6,000 = Laboratory Services (based on one specimen/animal every 3 days )
From page 43...
... 43 TOTAL COSTS - STUDY PROPOSAL 1: EXPERI~:NTAL STUDY Bovines Swine Chickens $687, 600 383, 400 420, 7 50 $1, 491, 750 Any costs recovered from the sale of the animals could be returned to the contractor. OBSERVATIONAL STUDY Cost for the observational study will be dependent upon the arrangements that can be made with those commercial concerns willing to cooperate in the study and the sizes of the groups to be observed.
From page 44...
... Further studies would be required to measure the effects on human health resulting from increased prevalence in animals of R+ organisms or of Salmonella with pathogenicity for humans. If animals with al low initial prevalence of R+ enteric orga ~ obtained, the study ~nisms cannot be o DEainea ~ Ene scuay snouts De moored to Determine if the feeding of strictly monitored antimicrobial-free feed results in a decline in R+ prevalence.
From page 45...
... The percentage of Enterobacteriaceae that carry R factors mediating resistance to tetracycline in each fecal specimen should be ascertained by quantitative culture techniques. These techniques should be designed to detect a biologically important difference in the prevalence of tetracycline resistance factors in stool specimens obtained from the groups being compared.
From page 46...
... Consequently, they are exposed to the organisms (which are likely to be resistant in animals fed antimicrobials) , but unlike farm workers they are not exposed to dusts containing antimicrobials that might be ingested or inhaled, thereby exerting a selective pressure favoring resistant enteric or respiratory tract bacteria.
From page 47...
... Information on the task performed by the abattoir workers should be collected in order to determine their potential for exposure to enteric organisms. For each stool specimen, quantitative culture techniques should be used to determine the percentage of Enterobacteriaceae that carry R factors mediating resistance to tetracycline.
From page 48...
... If there is no indication of an important association between the exposure of animals to either subtherapeutic or therapeutic levels of antimicrobials and the development of resistant enteric organisms, or if exposure to bacteria from animals fails to influence the flora of humans, the possibility of detrimental effects on human health would not be sufficiently well established to justify widespread changes in the current use of antimicrobials throughout the meat industry. If either the vegetarian study or the abattoir study indicates that the carriage of resistant organisms by humans is associated with meat consumption or occupational exposure to bacteria from animals, more extensive evaluations of morbidity and mortality would be justified.
From page 49...
... These surveys would enable investigators to compare female meat processors who have bacteriuria with similarly infected women in an urban setting far removed from contact with livestock and to match cases and controls for age, race, parity, and antimicrobial history. Participating screening services should use uniform procedures and criteria to detect UTI's.
From page 50...
... Present health status of subject Antimicrobial history of subject and household members and pets during past 2 years Hospitalization history of subject during past 2 years Major illness of subject and household members during past 2 years Patients with UTI characterized by bacteria with resistance to antimicrobials should be compared with patients with UTI characterized only by antimicrobial-sensitive bacteria to deters mine whether there are differences in antimicrobial history, in exposure to animals or carcasses that had been in contact with antimicrobials, or in exposure to feeds containing antimicrobials. Interpretation of Results If women with resistant enteric flora have a relatively high risk of a UTI compared to those without resistant fecal flora, the prevalence of R+ fecal flora among new cases should be greater than that among comparable controls.
From page 51...
... The comparison of UTI prevalence between groups with high and low exposure to R+ enteric organisms would provide some indication of the amount of primary UTI that is attributable to an occupational exposure. With a sufficiently large control group and high risk + groups in proximity to animals or carcasses with high levels of R organisms, a positive result would enable some conclusions to be drawn about total antimicrobial use in animals and UTI in humans caused by antimicrobial-resistant bacteria.


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