This document discusses antimicrobial resistance as a major infectious disease threat to public health. It notes that while antibiotics and other public health measures have led to declines in infectious disease deaths, antimicrobial resistance is now a growing problem affecting both healthcare and community settings. The document emphasizes that inappropriate antibiotic prescribing, particularly the overuse and misuse of broad-spectrum antibiotics, is the most important driver of growing resistance. Other factors like agricultural use of antibiotics can also contribute to the spread of resistant bacteria. A multifaceted approach is needed to address antimicrobial resistance that includes optimizing antibiotic use in humans and animals as well as public education campaigns.
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ND Health Officer Discusses Antimicrobial Resistance and Stewardship
1. Terry L Dwelle MD MPHTM FAAP CPH
State Health Officer
North Dakota Department of Health
2.
Antibiotics first employed in the 1940’s
Antibiotics + Vaccination + Sanitation =
Marked decline in deaths from ID’s
Antimicrobial resistance is a major ID threat to
PH
Much attention given to nosocomial infections
– ie VRE
Community acquired resistance is rising – St
Pneu., E Coli, Salmonella, etc.
Is an evolving problem – spans all health care
settings.
2
6.
160 days of illness per year
½ of the 10.9 million deaths per year
Magnifies the effect of diseases like measles
and malaria
7.
Swine – 3-9% improved weight gain, 3-7%
improved feed efficiency.
Greatest benefit when feed
composition, management practices and health
status of animals is not optimal.
Action
Eliminate bacteria that steal essential nutrients
Reduce competition with beneficial bacteria that produce
essential nutrients for the animal.
Control growth of bacteria that cause low-grade
infections or produce toxins – decreasing nutrient
absorption.
10.
Inappropriate antimicrobial prescribing – most
important
Overuse – 30-60% prescriptions are inappropriate
Inappropriate dosing
Use of broad spectrum AB’s as first line Rx
Animal applications (food)
10
12. •
•
•
•
46% of patients with common cold or nonspecific URI’s received antibiotics
Broad spectrum antibiotics used; 54%
general, 51% colds, 53% sinusitis, 62% acute
bronchitis, 65% OM
Lower BS use – blacks, lack of insurance, HMO
membership
Greater use of BS- Northeast and South
JAMA 2003;289:719-725
12
13.
12% recently taken antibiotics
27% believed taking antibiotics during a cold
made them better
32% believed taking antibiotics during a cold
prevented more serious illness
48% expected antibiotics when seeking medical
care with a cold
58% not aware of the health risks of antibiotics
Emerg Inf Dis: 9;9, pp 1128-1134 – JD Eng, et al
13
14.
Human health hazards
Antibiotic resistance particularly with low dosing
(ie Salmonella)
Glycopeptide resistant E faecium of animal origin
– find in stools for 14 + days after ingestion of
meat
Cross resistance
ie Virginimycin and Quinupristin-dalfopristin in
enterococci
Sorensen TL, NEJM 2001;3435:1161-6, Welton LA et al AntiAgChem
1998;42:705-8
14
16.
Europe – 1990’s – Avoparin use associated with
vancomycin resistance in humans
US – 1990’s – Campylobacter resistance to
fluoroquinolones
17.
Use antibiotics only when indicated
Least broad spectrum antibiotics first
Least time exposure possible
Use adequate therapeutic doses
Use non-human antibiotics when possible
With crossover drugs use those where
potential resistance will have the least impact
on humans
Appropriately monitor cultures and
sensitivities
18.
PRSP rose from 0% (1988) to 20% (1993)
Information campaign – physicians
Regulatory change – patients paid for
prescription drugs
PRSP declined to 15% (1995)
Stephenson J, JAMA 1996;275-175, Gunnlaugsson A, AntiAgChem
Conf, 1999, Abstract 1026
18
19.
Macrolide use tripled in the 1980’s
Erythromycin resistance for Gp A strep rose
sharply (17%) in the early 1990’s
National campaign for physicians
Resistance declined to 9% from 1992 to 1996
19
20.
1980’s
Appropriate use of advanced spectrum
antibiotics – 65%
All advanced spectrum antibiotic orders
received a form to be completed within 24
hours (justification of usage)
No adequate response – consult or could result
in loss of privileges
Appropriate use increased to > 95%
20
21.
Europe – Vancomycin resistance
Denmark – reduction in resistance in E
Faecium in broiler chickens (from 60-80% to 535%) WHO Internation Panel Ruling, Nov,
2002)
22.
Public Information Campaigns
Intensive Information Campaigns for
Physicians
Proactive Hospital Antibiotic Usage Programs
Collaborative task force –
Veterinarians, Physicians, and Public Health
22
Hinweis der Redaktion
This talk is about antimicrobial resistanceWhat can we do in human and veterinary medicine to control this issue.
This slide just lists the major antibiotic categories we utilize now – 71 years after Florey and Chain. Aminoglycosides – gentamicin, neomycin, kanamycin Beta lactams – penicillins (peni, amox, amp, augmentin), cephalosporins (1sr, 2nd, 3rd generation), carbapenems (imipenem, meropenem, doripenem), monbactams (aztreonam, tigemonam,nocardicin A, tabtoxin)Flouroquinolones (cipro, levoflox, moxifloxicin, naldixic acid)Glycopeptides (vancomycin, avoparcin)Ketolides (telithromycin,cethromycin, selithromycin)Lincosamides (lincomycin, clindamycin) Macrolides (erythromycin, azithromycin, vilprafen, tylosin)Oxazolidinones (linizolid, posizolid,torezolid, radezolid, cycloserine)Streptogramins (quinupristin/dalfopristin, pristinamycin, virginiamycin) Sulfonamides (sulfamethoxazole, sulfadiazine, sulfacetamide, sulfadoxime)Tetracyclines (demeclocycline, doxycycline, minocycline)Levomycetinums – (chloramphenicol)Ionophores– (A23187, Beauvericin, Calcimycine, Enniatin, Gramicidin A, Ionomycin, Lasalocid, Monensin, Nigericin, Nonactic, Nystatin, Salinomycin, Valinomycin) – inhibit various membrane ions from transfering. Bambermycins – (flavophosphlipols, moenomycins A and C) from streptomycesbambergiensis – used in animal feeds – swine, poultry, cattle.Polypeptides – (bacitracin)The field of antibiotics is vast - not only for human use but animal use.
Why do we use antibiotics?Treat infections – animals and humansPrevent infections Humans - surgical wounds, dental prophylaxis for endocarditis, neutropeniaAnimals – prevent disease when animals are susceptiblePromote growth – cattle, poultry and swineHelp meet the food needs for a growing world – significant concern
This is estimated data from 2010There were 925 million hungry people worldwide in 2010 (13.7% of the 6.8 billion people in the world);88% SS Africa, Asia and Pacific
Children are the greatest at risk group for undernutrition / malnutritionMalnourished - 160 days of illness per yearMalnutrition associated - ½ of the 10.9 million deaths per year Malnutrition - magnifies the effect of diseases like measles and malariaDiseases like diarrhea, measles, malaria and pneumonia may exacerbate or cause malnutrition. Adequate food production for the expanding population particularly children who are growing is key. Animal proteins are more bioavailable that plant proteins – amino acid profiles of animal proteins – more similar to human profiles therefore more easily absorbed. Increasing animal and plant protein in important for the future of the world – deal with human hunger issues.
Antibiotics and animal growthStudies from the 1950’s – animals given low does of antibiotics for a long time – gained more weight for a given amount of feed versus untreated animals.Swine – 3-9% improved weight gain with a 3-7% improvement in feed efficiency versus those not given low does of antibiotics.Greatest benefit when feed composition, management practices and health status of animals is not optimal.Studies suggest - no benefit is seen when these factors are optimal. Potential action – antibiotics and animal growthEliminate bacteria that steal essential nutrientsReduce competition with beneficial bacteria that produce essential nutrients for the animal.Control growth of bacteria that cause low-grade infections or produce toxins – decreasing nutrient absorption.
This lists some common antibiotics used in both human medicine and also used to stimulate animal growth.Tetracyclines (chlortetracycline)SulfonamidesPenicillins (penicillin)Macrolides (tylosin)FluoroquinolonesCephalosporinsAminoglycosidesChloramphenicolsStreptogramins (virginiamycin)Polypeptides (bacitracin)The second column lists the antibiotics used almost exclusively for animal growthIonophores (lasalocid,monesin) BambermycinsDepending - choice of antibiotics for supporting animal growth - significant overlap in many categories except for the ionophores – Nystatin used in candidiasis- and bambermycins. Choice is important.
This slide just lists some of the orgranisms that have caused concern due to development of resistance over the past few decades.Strep. Pneumoniae– peni,ceph, ery, quinolonesMoraxella Catarrhalis and Hem Influenza Type B – beta lactamase producers – attacks beta lactam antibiotics (peni, ceph, monobactams, carbapenams)Strep Pyogenes – Ery, fortunately peni sensitivity remains E. Coli – amp, t/s, quinolonesNeis. Gonorrhea – Peni, quinolones (cipro), cephNeis. Meningitidis– Peni (Spain – 71% in 1997)Campylobacter – C. Jejuni - Cipro (Spain 75-81% in 1998, Thailand – 84% in 1995)Salmonella – Amp, chloro, tetra, sulfonamides – DT104 decreased sens quinolones in Europe – rising ceph – 27% S typhimurium resist 5+ antibiotics. NEJM study 2001 – Ground meat – 20% samples + for Sal – 53% resist at least 3 antibiotics – 16% resist ceftriaxoneShigella – Minn, 1999 – 85% not suscept amp, 25% resist T/SStaph Aureus – MRSA 19-80% colonization – group studied (Samoan’s, N Amer, develop disabled residents – 45% resist to mupirocin.Enterococcus - VREMycobacterium Tuberculosis – MDR and XDRPertussis – Ery (Minn, 2000)
Another study – adults and children – 2003 -confirms46% of patients with common cold or non-specific URI’s received antibioticsBroad spectrum antibiotics – narrower spectrum could have been used.
Europe – 1990’s – Avoparin – glycopeptide - use to boost growth characteristics of chickens and pigs Avoparin resistant bacteria emerged in these animals Vancomycin resistance in humans noted at the same time.European Union banned use of avoparin to improve animal growth in 1997.Avoparin resistant bacteria in poultry and swine decreased to near zero.Resistance to vancomycin in humans saw an identical drop Resistance can be reversed.US – 1990’s – Campylobacter resistance to fluoroquinolones - increasedCamplylobacter is a commensal in the intestine of chickens.People can get infected by eating undercooked chicken - diarrhea1989 – none of the Campylobacter strains from ill people were fluoroquinolone resistant.1995 the FDA approve the use of quinolones in poultry.Soon afterward Campy strains from ill humans were noted resistant to quinolones. Doubt coincidence
Use antibiotics only when indicatedUtilize the least broad spectrum antibiotic possibleUse antibiotics for the least amount of time possible – This decreases the time organisms have to develop resistance mechanisms.Use adequate therapeutic doses (e.g. adequate doses of amox can actually treat intermediate resistant peni resistant St. Pneumo)The last two are particularly related to animal usage.Use non-human categories in animals when possible (ionophores, bambermycins)When using crossover drugs (used in both animals and humans) use antibiotics in animals that will have the least impact on humans – If resistance occurs it will influence the least number of people possible.Appropriately monitor cultures and sensitivities. Many human clinicians use non-culture techniques to diagnose and commonly fail to survey for sensitivities via culture.
Maintaining resistance takes energy.When antibiotic exposure is reduced below some threshold, antibiotic resistance decreases.Europe – FollowingAvoparin being banned, vancomycin resistance in humans decreased.Denmark – reduction in resistance in E Faecium in broiler chickens (from 60-80% to 5-35%) WHO Internation Panel Ruling, Nov, 2002)