Reference List
1. Aarestrup FM, Seyfarth AM, Emborg HD, Pedersen K,
Hendriksen RS, and Bager F: Effect of abolishment of the use of antimicrobial
agents for growth promotion on occurrence of antimicrobial resistance in
fecal enterococci from food animals in Denmark. Antimicrob Agents Chemother
2001, 45: 2054-2059
Ref ID: 955
Abstract: From 1995 to 2000, a total of 673 Enterococcus faecium and 1,088
Enterococcus faecalis isolates from pigs together with 856 E. faecium isolates
from broilers were isolated and tested for susceptibility to four classes
of antimicrobial agents used for growth promotion as part of the Danish program
of monitoring for antimicrobial resistance. The four antimicrobials were avilamycin,
erythromycin, vancomycin, and virginiamycin. Major changes in the use of
antimicrobial agents for growth promotion have occurred during the last 6
years in Denmark. The government banned the use of avoparcin in 1995 and
of virginiamycin in 1998. Furthermore, the producers have voluntarily stopped
all use beginning in 1999. The avoparcin ban in 1995 was followed by a decrease
in the occurrence of glycopeptide-resistant E. faecium (GRE) in broilers,
from 72.7% in 1995 to 5.8% in 2000. The occurrence of glycopeptide resistance
among isolates from pigs remained constant at around 20% from 1995 to 1997.
It was shown that, in GRE from pigs, the genes encoding macrolide and glycopeptide
resistance were genetically linked and that, following the decrease in the
use of tylosin during 1998 and 1999, the occurrence of GRE in pigs decreased
to 6.0% in 2000. From 1995 to 1997 the occurrence of erythromycin resistance
among E. faecium and E. faecalis isolates from pigs was almost 90%. Use of
tylosin decreased considerably during 1998 and 1999, and this decrease was
followed by decreases in the occurrence of resistance to 46.7 and 28.1% among
E. faecium and E. faecalis isolates from pigs, respectively. Erythromycin
resistance among E. faecium isolates from broilers reached a maximum of 76.3%
in 1997 but decreased to 12.7% in 2000 concomitantly with more limited use
of virginiamycin. Use of virginiamycin increased from 1995 to 1997 and was
followed by an increased occurrence of virginiamycin resistance among E.
faecium isolates in broilers, from 27.3% in 1995 to 66.2% in 1997. In January
1998 the use of virginiamycin was banned in Denmark, and the occurrence of
virginiamycin resistance decreased to 33.9% in 2000. Use of avilamycin increased
from 1995 to 1996 and was followed by an increase in avilamycin resistance
among E. faecium isolates from broilers, from 63.6% in 1995 to 77.4% in 1996.
Since 1996 avilamycin usage has decreased, followed by a decrease in resistance
to 4.8% in 2000. Our observations show that it is possible to reduce the
occurrence of antimicrobial resistance in a national population of food animals
when the selective pressure is removed. Cases in which resistance to vancomycin
was linked to resistance to erythromycin were exceptions. In such cases resistance
did not decrease until the use of both avoparcin and tylosin was limited
2. Aiello AE and Larson E: Antibacterial cleaning and
hygiene products as an emerging risk factor for antibiotic resistance in the
community. Lancet Infect Dis 2003, 3: 501-506
Ref ID: 888
Abstract: Antibiotic resistance within the community setting is an emerging
public-health concern. Infection with antibiotic-resistant organisms in the
community among people lacking traditional risk factors has been reported.
In addition, prevalence studies have identified individuals carrying antibiotic-resistant
organisms in the absence of known risk factors. These studies strongly suggest
the presence of contributing factors that have yet to be identified. In this
paper we review the burden of antibiotic resistance and known risk factors
within the community setting, assess the potential role of antibacterial cleaning
and hygiene products containing triclosan in the emergence of resistance,
and recommend future research on the assessment of household cleaning and
hygiene products containing triclosan
3. Allen KJ and Poppe C: Phenotypic and genotypic characterization
of food animal isolates of Salmonella with reduced sensitivity to ciprofloxacin.
Microb Drug Resist 2002, 8: 375-383
Ref ID: 990
Abstract: Reports of nontyphoidal Salmonella enterica subsp. enterica showing
reduced sensitivity to ciprofloxacin (RSC) have increased rapidly during the
past decade. Infection in humans with Salmonella possessing RSC may compromise
the effectiveness of ciprofloxacin therapy. Nineteen among 4,357 Salmonella
strains isolated from food animals in Canada from 1998 to 1999 showed RSC;
17 were from turkeys and 2 from chickens. All were resistant to nalidixic
acid and sulfisoxazole and possessed RSC at a level of 0.125-0.5 microg/ml.
PCR-RFLP of the gyrA quinolone resistance-determining region (QRDR) with Hinfl
revealed that S. Bredeney and S. Heidelberg isolates possessed a mutation
in this region. Single-strand conformational polymorphism (SSCP) analysis
showed that S. Schwarzengrund and S. Senftenberg isolates also possessed a
point mutation in the QRDR. DNA sequencing confirmed the findings and showed
that all isolates possessed a base substitution in the gyrA QRDR. Sequencing
revealed no mutations in the gyrB and silent wobble mutations in the parC
QRDR. Reserpine, a known efflux pump inhibitor, did not effect the MICs for
ciprofloxacin, nalidixic acid, and tetracycline. The mar operon could be induced
in all isolates at 37 degrees C and in 18 of 19 at 30 degrees C; induction
resulted in a two- to four-fold increase in the MIC of ciprofloxacin. In
14 of the 19 isolates, the mutation rate was two-fold or higher than in a
ciprofloxacin sensitive S. Bredeney and S. Typhimurium LT2 control strain.
Examination of clonal relatedness using pulsed-field gel electrophoresis (PFGE)
and plasmid profiles indicated that some degree of clonal dispersion may
have occurred, but the majority of isolates may have arisen from de novo mutations
4. Austin DJ, Bonten MJ, Weinstein RA, Slaughter S, and
Anderson RM: Vancomycin-resistant enterococci in intensive-care hospital settings:
transmission dynamics, persistence, and the impact of infection control programs.
Proc Natl Acad Sci U S A 1999, 96: 6908-6913
Ref ID: 30
Abstract: Vancomycin-resistant enterococci (VRE) recently have emerged as
a nosocomial pathogen especially in intensive-care units (ICUs) worldwide.
Transmission via the hands of health-care workers is an important determinant
of spread and persistence in a VRE-endemic ICU. We describe the transmission
of nosocomial pathogens by using a micro-epidemiological framework based on
the transmission dynamics of vector-borne diseases. By using the concept of
a basic reproductive number, R0, defined as the average number of secondary
cases generated by one primary case, we show quantitatively how infection
control measures such as hand washing, cohorting, and antibiotic restriction
affect nosocomial cross-transmission. By using detailed molecular epidemiological
surveillance and compliance monitoring, we found that the estimated basic
reproductive number for VRE during a study at the Cook County Hospital, Chicago,
was approximately 3-4 without infection control and 0.7 when infection control
measures were included. The impact of infection control was to reduce the
prevalence from a predicted 79% to an observed 36%. Hand washing and staff
cohorting are the most powerful control measures although their efficacy depends
on the magnitude of R0. Under the circumstances tested, endemicity of VRE
was stabilized despite infection control measures, by the constant introduction
of colonized patients. Multiple stochastic simulations of the model revealed
excellent agreement with observed pattern. In conjunction with detailed microbiological
surveillance, a mathematical framework provides a precise template to describe
the colonization dynamics of VRE in ICUs and impact of infection control
measures. Our analyses suggest that compliance for hand washing significantly
in excess of reported levels, or the cohorting of nursing staff, are needed
to prevent nosocomial transmission of VRE in endemic settings. ZZ
5. Austin DJ and Anderson RM: Studies of antibiotic resistance
within the patient, hospitals and the community using simple mathematical
models. Philos Trans R Soc Lond B Biol Sci 1999, 354: 721-738
Ref ID: 31
Abstract: The emergence of antibiotic resistance in a wide variety of important
pathogens of humans presents a worldwide threat to public health. This paper
describes recent work on the use of mathematical models of the emergence and
spread of resistance bacteria, on scales ranging from within the patient,
in hospitals and within communities of people. Model development starts within
the treated patient, and pharmacokinetic and pharmacodynamic principles are
melded within a framework that mirrors the interaction between bacterial population
growth, drug treatment and the immunological responses targeted at the pathogen.
The model helps identify areas in which more precise information is needed,
particularly in the context of how drugs influence pathogen birth and death
rates (pharmacodynamics). The next area addressed is the spread of multiply
drug-resistant bacteria in hospital settings. Models of the transmission dynamics
of the pathogen provide a framework for assessing the relative merits of
different forms of intervention, and provide criteria for control or eradication.
The model is applied to the spread of vancomycin-resistant enterococci in
an intensive care setting. This model framework is generalized to consider
the spread of resistant organisms between hospitals. The model framework allows
for heterogeneity in hospital size and highlights the importance of large
hospitals in the maintenance of resistant organisms within a defined country.
The spread of methicillin resistant Staphylococcus aureus (MRSA) in England
and Wales provides a template for model construction and analysis. The final
section addresses the emergence and spread of resistant organisms in communities
of people and the dependence on the intensity of selection as measured by
the volume or rate of drug use. Model output is fitted to data for Finland
and Iceland and conclusions drawn concerning the key factors determining
the rate of spread and decay once drug pressure is relaxed. ZZ
6. Austin DJ and Anderson RM: Transmission dynamics of
epidemic methicillin-resistant Staphylococcus aureus and vancomycin-resistant
enterococci in England and Wales. J Infect Dis 1999, 179: 883-891
Ref ID: 32
Abstract: A simple epidemiological framework for the analysis of the transmission
dynamics of hospital outbreaks of epidemic methicillin-resistant Staphylococcus
aureus (EMRSA) and vancomycin-resistant enterococci (VRE) in hospitals in
England and Wales is presented. Epidemic strains EMRSA-15 and EMRSA-16 are
becoming endemic in hospitals in the United Kingdom, and theory predicts that
EMRSA-15 and EMRSA-16 will reach respective endemic levels of 158 (95% confidence
interval [CI], 143-173) and 116 (95% CI, 109-123) affected hospitals with
stochastic fluctuations of up to 30 hospitals in each case. An epidemic of
VRE is still at an early stage, and the incidence of hospitals newly affected
by VRE is growing exponentially at a rate r=0.51/year (95% CI, 0.48-0.54).
The likely impact of introducing surveillance policies if action is taken
sufficiently early is estimated. Finally, the role of heterogeneity in hospital
size is considered: "Super-spreader hospitals" may increase transmission by
40%-132% above the expected mean. ZZ
7. Baquero F, Negri MC, Morosini MI, and Blâazquez
J: The antibiotic selective process: concentration-specific amplification
of low-level resistant populations. Ciba Found Symp 1997, 207: 93-105
Ref ID: 301
Abstract: The biochemistry and genetics of antibiotic resistance are far
better known than the equally important events underlying the selection of
resistant populations. The hidden selection of low-level resistant variants
may be a key process in the emergence of high-level antibiotic resistance.
Different low-level resistant bacterial subpopulations may be specifically
selected by different low antibiotic concentrations. The space in the environment
(human body) where a given selective concentration exists represents the selective
compartment. For pharmacokinetic reasons, low antibiotic concentrations occur
in a larger selective compartment and persist longer than high antibiotic
concentrations. The specific selection of low-level variants by low concentrations
of antibiotic can be reproduced in experimental in vitro models using mixtures
of susceptible and low-level resistant populations. We demonstrated this in
Escherichia coli strains harbouring TEM-1, TEM-12 and TEM-10 beta-lactamases
challenged by cefotaxime, and also Streptococcus pneumoniae strains with various
levels of penicillin resistance challenged by amoxicillin or cefotaxime. In
both cases, four hours of antibiotic challenge produced selective peaks of
low-level resistant variant populations at low-level antibiotic concentrations.
We conclude that variants with small decreases in antibiotic susceptibility
may be fully selectable under in vivo circumstances; on the other hand, low-level
antibiotic concentrations may have a considerable selective effect on the
emergence of antibiotic resistance. ZZ
8. Besser TE, Hancock D, and Davis MA: The veterinarian's
role in controlling the emergence and dissemination of drug-resistant bacteria.
J Vet Med Educ 2003, 30: 136-139
Ref ID: 901
9. Bogo JL, Willems RJ, and van den Bogaard AE: Genetic
characterization of glycopeptide-resistant enterococci of human and animal
origin from mixed pig and poultry farms. Apmis 2003, 111: 669-672
Ref ID: 920
Abstract: Glycopeptide resistant enterococci (GRE) isolated from animals
and humans were characterised using both AFPL typing and genetic characterisation
of the glycopeptide resistance transposon Tn1546. All isolates were collected
in 1997 when the glycopeptide avoparcin was still being used as growth promoter.
All investigated animal isolates were from mixed pig and poultry farms in
the Netherlands and the human isolated from the farmers of these farms. A
total of 24 isolates were investigated. AFLP and Tn1546 typing revealed that
both pig and poultry related enterococcal and vanA transposon genotypes were
found among the human isolates indicating spread of glycopeptide resistance
from both pig and poultry to the farmers. These findings contradict previous
finding that showed that GRE recovered from the general population were genotypically
undistinguishable from GRE isolated from pigs but are in line with other studies
that demonstrated spread of GRE from poultry to farmers in poultry farms
10. Brooks MB, Morley PS, Dargatz DA, Hyatt DR, Salman
MD, and Akey BL: Survey of antimicrobial susceptibility testing practices
of veterinary diagnostic laboratories in the United States. J Am Vet Med Assoc
2003, 222: 168-173
Ref ID: 971
Abstract: OBJECTIVE: To describe antimicrobial susceptibility testing practices
of veterinary diagnostic laboratories in the United States and evaluate the
feasibility of collating this information for the purpose of monitoring antimicrobial
resistance in bacterial isolates from animals. DESIGN: Cross-sectional study.
PROCEDURES: A questionnaire was mailed to veterinary diagnostic laboratories
throughout the United States to identify those laboratories that conduct susceptibility
testing. Nonrespondent laboratories were followed up through telephone contact
and additional mailings. Data were gathered regarding methods of susceptibility
testing, standardization of methods, data management, and types of isolates
tested. RESULTS: Eighty-six of 113 (76%) laboratories responded to the survey,
and 64 of the 86 (74%) routinely performed susceptibility testing on bacterial
isolates from animals. Thirty-four of the 36 (94%) laboratories accredited
by the American Association of Veterinary Laboratory Diagnosticians responded
to the survey. Laboratories reported testing > 160,000 bacterial isolates/y.
Fifty-one (88%) laboratories reported using the Kirby-Bauer disk diffusion
test to evaluate antimicrobial susceptibility; this accounted for 65% of
the isolates tested. Most (87%) laboratories used the NCCLS (National Committee
for Clinical Laboratory Standards) documents for test interpretation. Seventy-five
percent of the laboratories performed susceptibility testing on bacterial
isolates only when they were potential pathogens. CONCLUSIONS: The veterinary
diagnostic laboratories represent a comprehensive source of data that is
not easily accessible in the United States. Variability in testing methods
and data storage would present challenges for data aggregation, summary, and
interpretation
11. Carlson SA and Ferris KE: Augmentation of antibiotic
resistance in Salmonella typhimurium DT104 following exposure to penicillin
derivatives. Vet Microbiol 2000, 73: 25-35
Ref ID: 471
Abstract: Antibiotic resistance in pathogenic bacteria has been a problem
in both developed and developing countries. This problem is especially evident
in Salmonella typhimurium, one of the most prevalent foodborne pathogens.
While performing in vitro gentamicin protection-based invasion assays, we
found that certain isolates of multiresistant S. typhimurium can be 'induced'
to exhibit new resistance profiles. That is, bacteria become resistant to
a wider range of antibiotics and they also exhibit quantitative increases
in MIC values for antibiotics that were part of their pre-induction antibiograms.
This 'induction' process involves growing the bacteria to stationary phase
in the presence of antibiotics such as ampicillin, amoxicillin or ticarcillin.
Since the isolates studied exhibited resistance to ampicillin, amoxicillin
and ticarcillin prior to exposing the bacteria to these antibiotics, the observed
phenomenon suggests that resistant Salmonella not only have a selective advantage
over non-resistant Salmonella but their resistance phenotypes can be accentuated
when an inappropriate antibiotic is used therapeutically
12. Couper MR: Strategies for the rational use of antimicrobials.
Clin Infect Dis 1997, 24 Suppl 1: S154-S156
Ref ID: 207
Abstract: The World Health Organization's (WHO) policy on drugs is based
on the essential-drug concept. In order that this policy specifically encompasses
antimicrobials, several steps must be taken. Adequate information on the management
of infectious diseases should be readily available to prescribers. Continuing
education of prescribers, provision of treatment guidelines, and accurate
product labeling are important as well. Unethical promotion of antimicrobial
products by pharmaceutical companies should be prohibited. Patterns of drug
resistance in important pathogens should be monitored. Attempts should be
made to monitor drug use in terms of both prescription and consumption. Systematic
interchange of information at the national and international levels within
defined networks is necessary. The pharmaceutical quality of antimicrobials
must be ensured through rigorous registration and enforcement procedures.
Collaboration between the pharmaceutical industry and academics must be ongoing.
The WHO is prepared to assist countries in developing strategies on the rational
use of antimicrobials. ZZ
13. Courvalin P: Transfer of antibiotic resistance genes
between gram-positive and gram-negative bacteria. Antimicrob Agents Chemother
1994, 38: 1447-1451
Ref ID: 110
14. Dancer SJ: The problem with cephalosporins. J Antimicrob
Chemother 2001, 48: 463-478
Ref ID: 947
Abstract: The cephalosporin antibiotics have become a major part of the
antibiotic formulary for hospitals in affluent countries. They are prescribed
for a wide variety of infections every day. Their undoubted popularity relies
upon lesser allergenic and toxicity risks as well as a broad spectrum of
activity. It is the latter feature, however, that encourages the selection
of microorganisms that are resistant to these agents. There are long-term
implications for the treatment and control of this heterogeneous group of
superinfections. When clinicians evaluate a septic patient, it is understandable
that they choose empirical therapy with a cephalosporin whilst awaiting microbiology
and other tests, since bacterial identification and antimicrobial testing
still usually require 24-48 h. The broad-spectrum capability of these drugs,
however, encourages rapid overgrowth of some microorganisms that are neither
eliminated nor inhibited by therapy. These organisms not only have pathogenic
potential, they may also be multiply resistant to antibiotics. This review
discusses the evidence that cephalosporin usage is the most important factor
in the selection and propagation of microorganisms such as Clostridium difficile,
methicillin-resistant Staphylococcus aureus, penicillin-resistant pneumococci,
multiply resistant coliforms and vancomycin-resistant enterococci, the continuing
increase of which threatens the future of antimicrobial therapy
15. Dancer SJ: How antibiotics can make us sick: the
less obvious adverse effects of antimicrobial chemotherapy. Lancet Infect
Dis 2004, 4: 611-619
Ref ID: 948
Abstract: Antimicrobial agents are associated with side-effects, which are
usually tolerated because the benefits of treatment outweigh the toxic effects.
Clinicians know about these side-effects but are less likely to understand
additional adverse events, such as the overgrowth of resistant microorganisms.
Overgrowth can itself precipitate a secondary infection, which can be more
difficult to treat. Resistant organisms then spread to other patients and
the environment, and contribute to increasing antimicrobial resistance worldwide.
Organisms exposed to antibiotics undergo molecular changes that might enhance
virulence. Enhanced pathogenicity would affect patients, particularly if the
organism is also multiply resistant. Clinicians have a responsibility to
select the correct antibiotic as soon as they have diagnosed infection, but
an absence of microbiological understanding and ignorance of the potential
environmental effects have contributed to inappropriate prescribing. The less
obvious results of antimicrobial consumption probably go unrecognised in
routine clinical care
16. Dewey CE, Cox BD, Straw BE, Bush EJ, and Hurd HS:
Associations between off-label feed additives and farm size, veterinary consultant
use, and animal age. Prev Vet Med 1997, 31: 133-146
Ref ID: 669
Abstract: Data from the United States National Swine Survey collected by
the National Animal Health Monitoring System were used to describe the use
of feed additives in swine feeds. Data were collected from 710 farms. The
concentration of feed additives expressed in grams per ton of complete feed
was described by stage of production, and the use of feed additives above
the labeled treatment levels (i.e. off-label) was identified. Of the 3328
feeds, about 79% contained feed additives used in the labeled manner. For
all classes of pigs, the prevalence of labeled feed additive use was greater
than 75%. Penicillin was used according to its label most often, followed
by apramycin, bacitracin, tetracyclines, lincomycin, and tylosin. Carbadox
had the highest prevalence of off-label use. Of the 699 feeds that included
feed additives in an off-label manner, about 57% included additives at greater
than the recommended concentrations or were fed to an incorrect class of pig.
About 56% of the feeds had off-label combinations of additives. Small farms
were more likely to use rations with no feed additives than intermediate or
large farms (P < 0.001). Of those farms using feed additives, the odds
of a small farm using all feed additives in the labeled manner was 7.7 times
that of an intermediate or large farm (P < 0.0001). After controlling for
herd size, producers who used a veterinary consultant were 2.1 times more
likely to use feeds with feed additives (P < 0.0001)
17. Emborg HD, Andersen JS, Seyfarth AM, and Wegener
HC: Relations between the consumption of antimicrobial growth promoters and
the occurrence of resistance among Enterococcus faecium isolated from broilers.
Epidemiol Infect 2004, 132: 95-105
Ref ID: 908
Abstract: The present study investigates, at farm level, the effect of the
time-span between sampling and the last time a particular antimicrobial growth
promoter (AGP) was included in the feed on the probability of selecting an
AGP-resistant Enterococcus faecium isolate from a broiler flock. The probability
that a randomly selected E. faecium isolate was resistant to avilamycin, erythromycin
or virginiamycin was 0.91, 0.92 and 0.84, respectively if the isolate originated
from a broiler flock fed either avilamycin- or virginiamycin-supplemented
feed. As the time-span between sampling and the last AGP consumption increased,
the probability of isolating an E. faecium isolate resistant to a particular
AGP decreased (probability <0.2 within 3-5 years after last exposure to
AGPs). The decrease in probability over time showed little farm-to-farm variation.
The number of times a particular AGP was given to previous flocks reared in
the same house had no effect on the probability of isolating a resistant isolate
18. Ferber D: Antibiotic resistance. WHO advises kicking
the livestock antibiotic habit. Science 2003, 301: 1027
Ref ID: 884
19. Fey PD, Safranek TJ, Rupp ME, Dunne EF, Ribot E,
Iwen PC, Bradford PA, Angulo FJ, and Hinrichs SH: Ceftriaxone-resistant salmonella
infection acquired by a child from cattle [see comments]. N Engl J Med 2000,
342: 1242-1249
Ref ID: 294
Abstract: BACKGROUND: The emergence of resistance to antimicrobial agents
within the salmonellae is a worldwide problem that has been associated with
the use of antibiotics in livestock. Resistance to ceftriaxone and the fluoroquinolones,
which are used to treat invasive salmonella infections, is rare in the United
States. We analyzed the molecular characteristics of a ceftriaxone-resistant
strain of Salmonella enterica serotype typhimurium isolated from a 12-year-old
boy with fever, abdominal pain, and diarrhea. METHODS: We used pulsed-field
gel electrophoresis and analysis of plasmids and beta-lactamases to compare
the ceftriaxone-resistant S. enterica serotype typhimurium from the child
with four isolates of this strain obtained from cattle during a local outbreak
of salmonellosis. RESULTS: The ceftriaxone-resistant isolate from the child
was indistinguishable from one of the isolates from cattle, which was also
resistant to ceftriaxone. Both ceftriaxone-resistant isolates were resistant
to 13 antimicrobial agents; all but one of the resistance determinants were
on a conjugative plasmid of 160 kb that encoded the functional group 1 beta-lactamase
CMY-2. Both ceftriaxone-resistant isolates were closely related to the three
other salmonella isolates obtained from cattle, all of which were susceptible
to ceftriaxone. CONCLUSIONS: This study provides additional evidence that
antibiotic-resistant strains of salmonella in the United States evolve primarily
in livestock. Resistance to ceftriaxone, the drug of choice for invasive salmonella
disease, is a public health concern, especially with respect to children,
since fluoroquinolones, which can also be used to treat this disease, are
not approved for use in children. ZZ
20. Goldsmith RS and Schur PM: Use of subtherapeutic
antibiotics in livestock (as supplements or feed additives) with the induction
of resistance in human bacterial pathogens, the magnitude and complexity
of the problem become increasingly clear. J Environ Health 2002, 65: 7, 21
Ref ID: 905
21. Gorbach SL: Antimicrobial use in animal feed--time
to stop. N Engl J Med 2001, 345: 1202-1203
Ref ID: 616
22. Guardabassi L, Schwarz S, and Lloyd DH: Pet animals
as reservoirs of antimicrobial-resistant bacteria: Review. J Antimicrob Chemother
2004, 54: 321-332
Ref ID: 940
Abstract: Pet animal numbers have substantially increased in modern society
and attention is increasingly devoted to pet welfare. Because of these changes,
antimicrobial agents are frequently used in small animal veterinary practice,
often including antimicrobial preparations used in human medicine, with heavy
use of broad-spectrum agents such as aminopenicillins plus clavulanic acid,
cephalosporins and fluoroquinolones. Several longitudinal studies conducted
at veterinary hospitals have indicated that resistance to various antimicrobial
agents has emerged amongst pet animal isolates of Staphylococcus intermedius,
Escherichia coli and other bacteria, including species with a potential for
zoonotic transmission and resistance phenotypes of clinical interest, such
as methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci
and multidrug-resistant Salmonella Typhimurium DT104. Based on a review of
the current literature, the role of pets in the dissemination of antimicrobial
resistance has been given little attention when compared with that of food
animals. A marked contrast is evident between the current policies on antimicrobial
usage in food and companion animals. Apart from a few countries where limited
data on antimicrobial usage and occurrence of resistance in bacteria from
pet animals are provided, national surveillance programmes only focus on food
animals. However, data on pet animals are clearly needed for guiding antimicrobial
use policy in small animal veterinary practice as well as for assessing the
risk of transmission of antimicrobial resistance to humans
23. Handwerger S, Raucher B, Altarac D, Monka J, Marchione
S, Singh KV, Murray BE, Wolff J, and Walters B: Nosocomial outbreak due to
Enterococcus faecium highly resistant to vancomycin, penicillin, and gentamicin.
Clin Infect Dis 1993, 16: 750-755
Ref ID: 63
Abstract: In October 1990, Enterococcus faecium that was highly resistant
to glycopeptides, penicillins, and aminoglycosides was isolated from the peritoneal
dialysis fluid from a patient in an intensive care unit. Over the following
6 months, multiresistant E. faecium organisms were isolated from cultures
of blood, urine, or surgical wound specimens from eight additional patients.
Surveillance cultures of groin and/or rectal swabs were positive for eight
of 37 patients and four of 62 employees at risk. Restriction endonuclease
digestion of chromosomal DNA from outbreak isolates was consistent with dissemination
of a single strain throughout the intensive care unit. Strict infection control
interventions contained the outbreak after several weeks. Review of patient
charts suggested that renal insufficiency, length of hospital stay, duration
of antibiotic treatment, and prior treatment with vancomycin were risks for
infection due to multiresistant E. faecium. The emergence of multiple-drug-resistant
enterococci presents serious infection control and therapeutic dilemmas. ZZ
24. Helms M, Vastrup P, Gerner-Smidt P, and Molbak K:
Excess mortality associated with antimicrobial drug-resistant Salmonella typhimurium.
Emerg Infect Dis 2002, 8: 490-495
Ref ID: 602
Abstract: In a matched cohort study, we determined the death rates associated
with drug resistance in Salmonella Typhimurium. We linked data from the Danish
Surveillance Registry for Enteric Pathogens with the Civil Registration System
and the Danish National Discharge Registry. By survival analysis, the 2-year
death rates were compared with a matched sample of the general Danish population,
after the data were adjusted for differences in comorbidity. In 2,047 patients
with S. Typhimurium, 59 deaths were identified. Patients with pansusceptible
strains of S. Typhimurium were 2.3 times more likely to die 2 years after
infection than persons in the general Danish population. Patients infected
with strains resistant to ampicillin, chloramphenicol, streptomycin, sulfonamide,
and tetracycline were 4.8 times (95% CI 2.2 to 10.2) more likely to die, whereas
quinolone resistance was associated with a mortality rate 10.3 times higher
than the general population
25. Hershberger E, Donabedian S, Konstantinou K, and
Zervos MJ: Quinupristin-dalfopristin resistance in gram-positive bacteria:
mechanism of resistance and epidemiology. Clin Infect Dis 2004, 38: 92-98
Ref ID: 912
Abstract: Antimicrobial resistance in gram-positive bacteria is a continuing
problem resulting in significant morbidity, mortality, and cost. Because of
this resistance, new antimicrobial agents have been needed. Quinupristin-dalfopristin
is a recently approved agent for treatment of these infections. Shortly after
its introduction into clinical medicine, resistance was reported. Resistance
can occur by one or more of several mechanisms, including enzymatic modification,
active transport of efflux mediated by an adenosine triphosphate-binding protein,
and alteration of the target site. Resistance is rare in isolates of staphylococci
and Enterococcus faecium from humans. Resistance is common in isolates recovered
from food animals and is related to the use of virginiamicin as a feed additive.
Considering the effect antimicrobial resistance has on human health, as well
as its economic impact, measures to preserve the usefulness of these agents
and delay the development of resistance are urgently needed
26. Kariuki S and Hart CA: Global aspects of antimicrobial-resistant
enteric bacteria. Curr Opin Infect Dis 2001, 14: 579-586
Ref ID: 1005
Abstract: Antibiotics have been considered to be safe and effective 'magic
bullets', with no disadvantages to their widespread use. This has been proven
to be a complacent attitude, with ever-increasing prevalences of resistance
now evident. The present review covers aspects of the development, mechanisms
and genetics of antimicrobial resistance in enteric commensals and pathogens
27. Kidd RS, Rossignol AM, and Gamroth MJ: Salmonella
and other Enterobacteriaceae in dairy-cow feed ingredients: antimicrobial
resistance in western Oregon. J Environ Health 2002, 64: 9-16, 32
Ref ID: 974
Abstract: Several studies have suggested an association between the use
of antimicrobial agents in animal feeds and an increased risk that humans
will contract resistant strains of bacteria such as Salmonella species, Escherichia
coli, and other enteric isolates. The authors of this study evaluated whether
animal feeds might serve as sources of antimicrobial-resistant bacteria, especially
bacteria that are pathogenic to humans. From July through August 1998, samples
of feed ingredients were collected from a total of 50 feed piles located
on 12 dairy farms in western Oregon. From a subset of 10 piles, repeated
samples were collected over time until each pile was depleted. Analysis of
the samples indicated that 42.0 percent of all 50 piles and 60.0 percent of
the piles from which there was repeated sampling were presumptive positive
for Salmonella. Sixty-two percent of 50 Enterobacteriaceae isolates showed
ampicillin resistance, and 10.0 percent displayed tetracycline resistance.
Other bacteria displayed varying degrees of resistance to ampicillin, streptomycin,
tetracycline, or a combination of these antimicrobials. The extent of antimicrobial-resistant
Enterobacteriaceae in feed ingredients observed in this study raises significant
concerns about the potential for human health risks from food-producing animals
such as dairy cows
28. Kollef MH and Fraser VJ: Antibiotic resistance in
the intensive care unit. Ann Intern Med 2001, 134: 298-314
Ref ID: 511
Abstract: Antimicrobial resistance has emerged as an important determinant
of outcome for patients in the intensive care unit (ICU). This is largely
due to the administration of inadequate antimicrobial treatment, which is
most often related to bacterial antibiotic resistance. In addition, the escalating
problem of antimicrobial resistance has substantially increased overall health
care costs. This increase is a result of prolonged hospitalizations and convalescence
associated with antibiotic treatment failures, the need to develop new antimicrobial
agents, and the implementation of broader infection control and public health
interventions aimed at curbing the spread of antibiotic-resistant pathogens.
Intensive care units are unique because they house seriously ill patients
in confined environments where antibiotic use is extremely common. They have
been focal points for the emergence and spread of antibiotic-resistant pathogens.
Effective strategies for the prevention of antimicrobial resistance in ICUs
have focused on limiting the unnecessary use of antibiotics and increasing
compliance with infection control practices. Clinicians caring for critically
ill patients should consider antimicrobial resistance as part of their routine
treatment plans. Careful, focused attention to this problem at the local ICU
level, using a multidisciplinary approach, will have the greatest likelihood
of limiting the development and dissemination of antibiotic-resistant infections.
ZZ
29. Lenski RE: The cost of antibiotic resistance--from
the perspective of a bacterium. Ciba Found Symp 1997, 207: 131-140
Ref ID: 408
Abstract: The possession of an antibiotic resistance gene clearly benefits
a bacterium when the corresponding antibiotic is present. But does the resistant
bacterium suffer a cost of resistance (i.e. a reduction in fitness) when the
antibiotic is absent? If so, then one strategy to control the spread of resistance
would be to suspend the use of a particular antibiotic until resistant genotypes
declined to low frequency. Numerous studies have indeed shown that resistant
genotypes are less fit than their sensitive counterparts in the absence of
antibiotic, indicating a cost of resistance. But there is an important caveat:
these studies have put antibiotic resistance genes into naive bacteria, which
have no evolutionary history of association with the resistance genes. An
important question, therefore, is whether bacteria can overcome the cost
of resistance by evolving adaptations that counteract the harmful side-effects
of resistance genes. In fact, several experiments have shown that the cost
of antibiotic resistance may be substantially diminished, even eliminated,
by evolutionary changes in bacteria over rather short periods of time. As
a consequence of this adaptation of bacteria to their resistance genes, it
becomes increasingly difficult to eliminate resistant genotypes simply by
suspending the use of antibiotics
30. Levy SB: Antibiotic resistance: an ecological imbalance.
Ciba Found Symp 1997, 207: 1-9
Ref ID: 131
Abstract: Antibiotic resistance thwarts the treatment of infectious diseases
worldwide. Although a number of factors can be identified which contribute
to the problem, clearly the antibiotic as a selective agent and the resistance
gene as the vehicle of resistance are the two most important, making up a
'drug resistance equation'. Both are needed in order for a clinical problem
to arise. Given sufficient time and quantity of antibiotic, drug resistance
will eventually appear. But a public health problem is not inevitable if the
two components of the drug resistance equation are kept in check. Enhancing
the emergence of resistance is the case by which resistance determinants and
resistant bacteria can spread locally and globally, selected by widespread
use of the same antibiotics in people, animal husbandry and agriculture. Antibiotics
are societal drugs. Each individual use contributes to the sum total of society's
antibiotic exposure. In a broader sense, the resistance problem is ecological.
In the framework of natural competition between susceptible and resistant
bacteria, antibiotic use has encouraged growth of the resistant strains,
leading to an imbalance in prior relationships between susceptible and resistant
bacteria. To restore efficacy to earlier antibiotics and to maintain the
success of new antibiotics that are introduced, we need to use antibiotics
in a way which assures an ecological balance that favours the predominance
of susceptible bacterial flora. ZZ
31. Levy SB: The Antibiotic Paradox: How the Misuse of
Antibiotics Destroys Their Curative Powers. Perseus Publishing, 2002
Ref ID: 620
32. Lipsitch M, Singer RS, and Levin
BR: Antibiotics in agriculture: when is it time to close the barn door? Proc
Natl Acad Sci U S A 2002, 99: 5752-5754
Ref ID: 997
33. McArthur JV and Tuckfield RC: Spatial patterns
in antibiotic resistance among stream bacteria: effects of industrial pollution.
Appl Environ Microbiol 2000, 66: 3722-3726
Ref ID: 672
Abstract: The spatial distribution of antibiotic resistance to streptomycin
and kanamycin was examined in natural bacterial communities of two streams.
The proportion of resistant bacteria was substantially higher (P < 0.05)
in the midreaches of an industrially perturbed stream, but no such pattern
was apparent in an undisturbed reference stream. The highest relative frequency
of resistance was found at the confluence of a tributary draining a nuclear
reactor and industrial complex. Antibiotic resistance increased with distance
upstream from the confluence and was positively correlated (r(2) = 0. 54,
P = 0.023) with mercury concentrations in the sediments. When the data for
two years were compared, this pattern was stable for streptomycin resistance
(paired t test, P < 0.05) but not for kanamycin resistance (P > 0.05).
Our results imply that heavy metal pollution may contribute to increased antibiotic
resistance through indirect selection
34. McGowan JJ and Gerding DN: Does antibiotic restriction
prevent resistance? New Horiz 1996, 4: 370-376
Ref ID: 381
Abstract: Antimicrobial resistance among some hospital organisms has increased
to a stage where it can no longer be tolerated. The need for preventive and
corrective measures is urgent. There is an association between the use of
antimicrobial agents and resistance that is likely causal. Alterations in
antimicrobial usage have been shown to affect antimicrobial resistance rates,
particularly with use of aminoglycosides. Efforts to improve antimicrobial
use through educational efforts alone have been largely ineffective, even
when coupled with quality management or clinical guideline aspects. Thus,
further work is urgently needed to determine the impact of antimicrobial-use
controls. Additional large-scale, well controlled trials of antimicrobial-use
regulation employing sophisticated epidemiologic methods, molecular biological
organism typing, and precise resistance mechanism analysis will be required
to determine the best methods to prevent and control this problem and ensure
our optimal antimicrobial-use "stewardship." Consideration of the long-term
effects of antimicrobial selection, dosage, and duration of treatment on resistance
development should be a part of every antimicrobial treatment decision. ZZ
35. Mellon M, Benbrook C, and Benbrook KL: Hogging it.
Estimates of Antimicrobial Abuse in Livestock. Cambridge. MA UCS Publications,
2001
Ref ID: 478
36. O'Brien TF: The global epidemic nature of antimicrobial
resistance and the need to monitor and manage it locally. Clin Infect Dis
1997, 24 Suppl 1: S2-S8
Ref ID: 151
Abstract: An antimicrobial agent may be used for years before a gene expressing
resistance to it emerges in a strain of bacteria somewhere. Progeny of that
strain, or of others to which the gene is transferred, may then disseminate
preferentially through global networks of bacterial populations on people
or animals treated with that agent or with other agents as the gene becomes
linked to genes expressing resistance to them. Over 100 resistance genes-varying
in their frequency of emergence, vectors, linkages, and pathways-have thus
emerged, reemerged, converged, and disseminated irregularly through the world's
bacterial ecosystems over the last 60 years to reach infecting strains and
block treatment of infection. We may delay emergence by using agents less
and retard dissemination by good hygiene, infection control measures, and
avoidance of agents that select for resistance genes in contiguous populations.
Local monitoring and management of resistance appear essential because of
the intricacies of tracing and targeting the problems at each place and because
national or global surveillance and strategy develop from local information
and understanding. ZZ
37. O'Brien TF: Emergence, spread, and environmental
effect of antimicrobial resistance: how use of an antimicrobial anywhere
can increase resistance to any antimicrobial anywhere else. Clin Infect Dis
2002, 34 Suppl 3: S78-S84
Ref ID: 599
Abstract: Use of an antimicrobial agent selects for overgrowth of a bacterial
strain that has a gene expressing resistance to the agent. It also selects
for the assembly and evolution of complex genetic vectors encoding, expressing,
linking, and spreading that and other resistance genes. Once evolved, a competitive
construct of such genetic elements may spread widely through the world's bacterial
populations. A bacterial isolate at any place may thus be resistant-not only
because nearby use of antimicrobials had amplified such a genetic construct
locally, but also because distant use had caused the construct or its components
to evolve in the first place and spread there. The levels of resistance at
any time and place may therefore reflect in part the total number of bacteria
in the world exposed to antimicrobials up until then. Tracing the evolution
and spread of such genetic elements through bacterial populations far from
one another, such as those of animals and humans, can be facilitated by newer
genetic methods
38. Phillips I, Casewell M, Cox T, De Groot B, Friis
C, Jones R, Nightingale C, Preston R, and Waddell J: Does the use of antibiotics
in food animals pose a risk to human health? A critical review of published
data. J Antimicrob Chemother 2004, 53: 28-52
Ref ID: 946
Abstract: The use of antibiotics in food animals selects for bacteria resistant
to antibiotics used in humans, and these might spread via the food to humans
and cause human infection, hence the banning of growth-promoters. The actual
danger seems small, and there might be disadvantages to human and to animal
health. The low dosages used for growth promotion are an unquantified hazard.
Although some antibiotics are used both in animals and humans, most of the
resistance problem in humans has arisen from human use. Resistance can be
selected in food animals, and resistant bacteria can contaminate animal-derived
food, but adequate cooking destroys them. How often they colonize the human
gut, and transfer resistance genes is not known. In zoonotic salmonellosis,
resistance may arise in animals or humans, but human cross-infection is common.
The case of campylobacter infection is less clear. The normal human faecal
flora can contain resistant enterococci, but indistinguishable strains in
animals and man are uncommon, possibly because most animal enterococci do
not establish themselves in the human intestine. There is no correlation between
the carriage of resistant enterococci of possible animal origin and human
infection with resistant strains. Commensal Escherichia coli also exhibits
host-animal preferences. Anti-Gram-positive growth promoters would be expected
to have little effect on most Gram-negative organisms. Even if resistant pathogens
do reach man, the clinical consequences of resistance may be small. The application
of the 'precautionary principle' is a non-scientific approach that assumes
that risk assessments will be carried out
39. Piddock LJ: Does the use of antimicrobial agents
in veterinary medicine and animal husbandry select antibiotic-resistant bacteria
that infect man and compromise antimicrobial chemotherapy? J Antimicrob Chemother
1996, 38: 1-3
Ref ID: 155
40. Randall LP, Cooles SW, Sayers AR, and Woodward MJ:
Association between cyclohexane resistance in Salmonella of different serovars
and increased resistance to multiple antibiotics, disinfectants and dyes.
J Med Microbiol 2001, 50: 919-924
Ref ID: 904
Abstract: A panel of 388 salmonellas of animal and human origin, comprising
35 serotypes, was tested for resistance to cyclohexane and to a range of antibiotics,
disinfectants and dyes. Cyclohexane resistance was detected in 41 isolates
(10.6%): these comprised members of the serovars Binza (1 of
15), Dublin (1 of 24), Enteritidis (1 of 61), Fischerkietz (4 of 5), Livingstone
(9 of 11), Montevideo (1 of 32), Newport (4 of 23), Saint-paul (1 of 3), Senftenberg
(10 of 24) and Typhimurium (9 of 93). Most (39 of 41) of the cyclohexane-resistant
isolates were from poultry. Statistical analysis showed that the cyclohexane-resistant
strains were significantly more resistant than the cyclohexane-susceptible
strains to ampicillin, chloramphenicol, ciprofloxacin, erythromycin, nalidixic
acid, tetracycline, trimethoprim, cetrimide and triclosan. The multiresistance
patterns seen were typical of those caused by efflux pumps, such as AcrAB.
The emergence of such resistance may play an important role in the overall
antibiotic resistance picture of Salmonella, with particular effect on ciprofloxacin
41. Rubin RJ, Harrington CA, Poon A, Dietrich K, Greene
JA, and Moiduddin A: The economic impact of Staphylococcus aureus infection
in New York City hospitals. Emerg Infect Dis 1999, 5: 9-17
Ref ID: 382
Abstract: We modeled estimates of the incidence, deaths, and direct medical
costs of Staphylococcus aureus infections in hospitalized patients in the
New York City metropolitan area in 1995 by using hospital discharge data collected
by the New York State Department of Health and standard sources for the costs
of health care. We also examined the relative impact of methicillin-resistant
versus -sensitive strains of S. aureus and of community-acquired versus nosocomial
infections. S. aureus-associated hospitalizations resulted in approximately
twice the length of stay, deaths, and medical costs of typical hospitalizations;
methicillin-resistant and -sensitive infections had similar direct medical
costs, but resistant infections caused more deaths (21% versus 8%). Community-acquired
and nosocomial infections had similar death rates, but community-acquired
infections appeared to have increased direct medical costs per patient ($35,300
versus $28,800). The results of our study indicate that reducing the incidence
of methicillin-resistant and -sensitive nosocomial infections would reduce
the societal costs of S. aureus infection. ZZ
42. Salyers AA: An overview of the genetic basis of antibiotic
resistance in bacteria and its implications for agriculture. Anim Biotechnol
2002, 13: 1-5
Ref ID: 951
43. Stock I and Wiedemann B: Natural antibiotic susceptibility
of Salmonella enterica strains. Int J Antimicrob Agents 2000, 16: 211-217
Ref ID: 506
Abstract: The susceptibility of 100 Salmonella enterica strains belonging
to S. enterica subsp. enterica (n=90) and S. enterica subsp. arizonae (n=10)
was examined to 71 antibiotics. Within S. enterica subsp. enterica, strains
of different serovars (typhimurium (n=17), enteritidis (n=17), dublin (n=10),
typhi (n=16), paratyphi A (n=6), others (n=24)) were studied. MICs were determined
using a microdilution procedure and apart from fosfomycin there were no significant
differences in susceptibility between the subspecies and serovars of S. enterica.
All salmonellae were sensitive or intermediately resistant to tetracyclines,
aminoglycosides, most beta-lactam antibiotics, quinolones, co- trimoxazole
group antibiotics, chloramphenicol, nitrofurantoin and azithromycin. S. enterica
strains were intrinsically resistant to benzylpenicillin, oxacillin, most
macrolides, rifampicin, lincosamides, streptogramins, glycopeptides and fusidic
acid. Apart from some slight differences in antibiotic susceptibility between
strains of S. enterica subsp. enterica and S. enterica subsp. arizonae, only
the susceptibility to fosfomycin varied among the taxa studied. Whereas 'enteric'
salmonellae including S. enterica subsp. arizonae were sensitive to fosfomycin,
'typhoid' salmonellae were intrinsically resistant. A database of the antibiotic
susceptibility of S. enterica was set up. It may be of use to validate antibiotic
susceptibility test results of these bacteria
44. SŽaenz Y, Zarazaga M, Lantero M, Gastanares MJ, Baquero
F, and Torres C: Antibiotic resistance in Campylobacter strains isolated from
animals, foods, and humans in Spain in 1997-1998. Antimicrob Agents Chemother
2000, 44: 267-271
Ref ID: 565
Abstract: Colonization by Campylobacter strains was investigated in human,
broiler, and pig fecal samples from 1997-1998, as well as in foods of animal
origin, and antibiotic susceptibility testing was carried out for these strains.
Campylobacter strains were isolated in the foods of animal origin (55 of 101
samples; 54.4%), intestinal samples from broilers (85 of 105; 81%), and pigs
(40 of 45; 88.9%). A total of 641 Campylobacter strains were isolated from
8,636 human fecal samples of clinical origin (7.4%). Campylobacter jejuni
was the most frequently isolated species from broilers (81%) and humans (84%),
and Campylobacter coli was most frequently isolated from pigs (100%). An extremely
high frequency of ciprofloxacin resistance was detected among Campylobacter
strains, particularly those isolated from broilers and pigs (99%), with a
slightly lower result for humans (72%); cross-resistance with nalidixic acid
was almost always observed. A higher frequency of resistance to erythromycin
(81.1%), ampicillin (65.7%), gentamicin (22.2%), and amikacin (21.6%) was
detected in C. coli strains isolated from pigs compared to those isolated
from humans (34.5, 29.3, 8.6, and 0%, respectively). A low frequency of erythromycin
resistance was found in C. jejuni or C. coli isolated from broilers. A greater
resistance to ampicillin and gentamicin (47.4 and 11.9%, respectively) was
detected in C. jejuni isolated from broilers than in human strains (38 and
0.4%, respectively). Beta-lactamase production was found in 81% of the Campylobacter
strains tested, although 44% of them were characterized as ampicillin susceptible.
The increasing rates of Campylobacter resistance make advisable a more conservative
policy for the use of antibiotics in farm animals
45. Teuber M: Veterinary use and antibiotic resistance.
Curr Opin Microbiol 2001, 4: 493-499
Ref ID: 623
Abstract: Globally, an estimated 50% of all antimicrobials serve veterinary
purposes. Bacteria that inevitably develop antibiotic resistance in animals
comprise food-borne pathogens, opportunistic pathogens and commensal bacteria.
The same antibiotic resistance genes and gene transfer mechanisms can be found
in the microfloras of animals and humans. Direct contact, food and water
link animal and human habitats. The accumulation of resistant bacteria by
the use of antibiotics in agriculture and veterinary medicine and the spread
of such bacteria via agriculture and direct contamination are documented
46. Tollefson L, Altekruse SF, and Potter ME: Therapeutic
antibiotics in animal feeds and antibiotic resistance. Rev Sci Tech 1997,
16: 709-715
Ref ID: 171
Abstract: Recent statutory changes involving animal drugs are expected to
facilitate the therapeutic use of antibiotics in animal feeds in the United
States of America. The use of antibiotics in animal feeds is controversial
due to the potential development of resistant bacterial pathogens in food-producing
animals which are exposed to the antibiotics and the resultant public health
risk. Zoonotic micro-organisms can be transmitted to humans through contact
with animal populations, either directly or through the consumption of contaminated
food. Recommendations to address the public health concerns include the strengthening
of professional education in the areas of infectious diseases and the appropriate
selection and use of antimicrobial agents, the development of a comprehensive
food safety education programme for food-animal veterinarians and animal producers,
and the development of surveillance programmes to monitor antimicrobial resistance
among zoonotic pathogens. Early identification of emerging resistance can
facilitate a timely and appropriate public health response. ZZ
47. Tollefson L and Miller MA: Antibiotic use in food
animals: controlling the human health impact. J AOAC Int 2000, 83: 245-254
Ref ID: 433
48. Torrence ME: Activities to address antimicrobial
resistance in the United States. Prev Vet Med 2001, 51: 37-49
Ref ID: 656
Abstract: Antimicrobials are essential for the prevention and treatment
of bacterial infections in humans and animals. Subtherapeutic antimicrobials
have been used as growth promoters for >40 years. The subject of antimicrobial
resistance is not new but has gained increasing attention due to public-health
concerns about multi-resistant pathogenic organisms. Numerous United States'
activities do exist to address antimicrobial resistance. A surveillance system
(the National Antimicrobial Resistance Monitoring System) was established
in 1996 to monitor changes over time in resistance for 17 antibiotics in humans
and animals. Educational campaigns have been created to promote the judicious
therapeutic use of antimicrobials. Producer groups are developing guidelines
for judicious therapeutic antimicrobial use for their prospective species.
Basic and applied research programs are being expanded to answer many of
the unsolved questions regarding development, persistence, and transmission
of antimicrobial resistance. This paper focuses on a federal inter-agency
public-health action plan to combat antimicrobial resistance; the plan was
released for public comment in 2000. This plan addresses goals and actions
to combat antimicrobial resistance in humans and agriculture in four areas:
surveillance; research; prevention and control; product development
49. Witte W: Selective pressure by antibiotic use
in livestock. Int J Antimicrob Agents 2000, 16 Suppl 1: S19-S24
Ref ID: 496
Abstract: Selective pressure exerted by the use of antibiotics as growth
promoters in food animals appears to have created large reservoirs of transferable
antibiotic resistance in these ecosystems. This first became evident for oxytetracycline
and later for the streptothricin antibiotic nurseothricin, for which a transfer
of relevant resistance determinants (sat genes) to bacterial pathogens of
humans was demonstrated. With the emergence of glycopeptide resistance in
Enterococcus faecium outside hospitals, a large reservoir of transferable
resistance (vanA gene cluster) was identified in animal husbandry due to
the use of avoparcin as feed additive. The spread of resistance, which reaches
the human enterococcal flora via meat products, is probably due to the dissemination
of the vanA gene cluster integrated into different conjugative plasmids among
a variety of different strains. Streptogramin resistance associated with
the resistance genes vatA and vatG has been found in E. faecium of animal
and of clinical origin. Because virginiamycin has been used as growth promoter
in animals but streptogramins have been used infrequently in human medicine,
this again suggests an animal origin of resistance. Since the use of avoparcin
ended, a decline in the rates of glycopeptide-resistant E. faecium (GREF)
from animals and humans in the community has been recorded. This supports
the ban of antibacterial growth promoters that might interfere with human
chemotherapy that has been introduced in European Union countries
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