md frcpc organisms – a canadian paediatric society. health...

rec om mended pro vided that the vac cine was ad min is teredprop erly (8).

The lack of uni ver sal ‘free’ catch- up pro grams is of con -cern. The longer the de lay in achiev ing a uni ver sally im mu -nized ado les cent popu la tion, the more new cases of hepa ti tisB will likely oc cur and the less con fi dence the pub lic will havein the pro gram. Our pro vin cial min is tries of health must lookclosely at meas ures to ex pand cov er age be yond these pre -ado les cent school- based pro grams. Un for tu nately, a uni ver -sal health care sys tem in which pre ven tion pro grams re ceivehigh pri or ity is still a long way from re al ity in Can ada (9).

REF ER ENCES1. Delage G, Carter AO. Hepatitis B infection in Canada.

Epidemiology and implications for control. Can Fam Physician1992;38:2656-6.

2. Alter MJ, Hadler SC, Margolis HS, et al. The changingepidemiology of hepatitis B in the United States. JAMA1990;263:1218-22.

3. National Advisory Committee on Immunization. Statement onuniversal immunization against hepatitis B. Can Dis Wkly Rep1991;17:165-72.

4. Infectious Disease and Immunization Committee, CanadianPaediatric Society. Hepatitis B in Canada: the case for universal immunization. Can Med Assoc J 1992;146:25-8.

5. Hepatitis Working Goup. Report of the Hepatitis Working Group.Can Dis Wkly Rep 1994;20:105-12.

6. Bloom BS, Hellman AI, Fendrick AM, et al. A reappraisal ofhepatitis B virus vaccination strategies using cost-effectivenessanalysis. Ann Intern Med 1993;118:298-306.

7. Dobson SR, Scheifele DW, Bell A. Evaluation of a universalhepatitis B vaccination program for adolescents in BritishColumbia. Pediatr Res 1993;33:167A. (Abst 982)

8. National Advisory Committee on Immunization. CanadianImmunization Guide, 4th edn. Ottawa: Health Canada,1993:46-57.

9. Infectious Disease and Immunization Committee, CanadianPaediatric Society. Health care budgets and vaccine programs:a time for review and prioritization. Can Med Assoc J1994;150:1555-6.

NE Mac Don ald MD FRCPC

Chief, Di vi sion of In fec tious Dis easeChil dren’s Hos pi tal of East ern On tario

Ot tawa, On tario

ADULT IN FEC TIOUS DIS EASE NOTES

Confronting antibiotic-resistantorganisms – A Canadian

perspectiveANTIBIOTIC- RESISTANT OR GAN ISMS (AROS) AND WITH THEM THE

threat of new and ree mer gent in fec tious dis eases are on the rise world wide. This ris ing tide of re sis tance to an ti mi cro -bial drugs has been re ferred to as a ‘worl dwide ca lam ity’ (1).Since the be gin ning of this dec ade, cli ni cians, mi cro bi olo gistsand pub lic health of fi cials have con fronted an un prece dentednumber of epi dem ics of ‘new’ in fec tious dis eases and re sur -gent ‘old’ in fec tious dis eases on a truly in ter na tional scale.Ex am ples are the han ta vi rus pul mo nary syn drome in theUnited States, hu man T cell lym pho trophic vi rus in the Car ib -bean, Sabia vi rus in Bra zil, Gua narito vi rus in Vene zuela,Escheri chia coli O157:H7 dis ease and cryptospo ridio sis in theUnited States, Vi brio chol erae 01 in Latin Amer ica and 0139in Asia, Rift Val ley fe ver in Egypt, multidrug- resistant tu ber cu -

lo sis in Asia and the United States, bu bonic plague in In dia,and AROs in Europe, Latin Amer ica and the United States(2,3). Of the ree merg ing in fec tious dis eases, AROs ar gua blyrep re sent the most im me di ate threat to hu man health andwel fare. The pros pect and in deed re al ity of at tempt ing to treatmul ti ply drug- resistant en te ro coc cal, pneu mo coc cal and tu -ber cu lous in fec tions have been brought to the at ten tion ofboth the sci en tific com mu nity and the lay press (3-5). Themost se ri ous threat is the ac qui si tion of re sis tance to van co -my cin ei ther by methicillin- resistant Staphy lo coc cus au reusor by mac rolide penicillin- resistant Strep to coc cus pneu mo -niae, which could cre ate in va sive clones for which there arefew or no eas ily avail able thera peu tic agents. The suc cess fultrans fer and ex pres sion of vancomy cin-r esi stant genes to S

In fec tious dis ease notes

130 CAN J INFECT DIS VOL 6 NO 3 MAY/JUNE 1995

au reus have been dem on strated in vi tro (6). The emer gence ofvan co my cin-r esi stant strains of S au reus in clini cal strainswas con sid ered to be only a mat ter of time and there are nowre ports of such strains in Vene zuela (7).

There are many spe cific ex am ples of AROs and the mostcom monly en coun tered or gan isms in clude mul ti ply drug- resistant My co bac te rium tu ber cu lo sis (8,9), methicillin- resistant S au reus (10), vancomycin- resistant en te ro cocci(11), penicillin- resistant pneu mo cocci (12,13), mul ti ply re sis -tant Shigella spe cies and Sal mo nella ty phi (14,15), ex tendedspec trum beta- lactam (in clud ing third- generation cepha lo -sporin re sis tance) re sis tant en teric Gram- negative ba cillisuch as Klebsiella- Enterobacter spe cies (16) and mul ti ply re -sis tant Aci ne to bac ter spe cies (17).

There are many rea sons for the emer gence of AROs, butclearly the re mark able and ex traor di nary ca pac ity for mi cro or -gan isms to adapt to their chang ing en vi ron ment is the mostim por tant fac tor. The Dar win ian the ory of evo lu tion with re -spect to ‘su rvival of the fit test’ may be no more aptly ap pliedthan in the set ting of mi cro or gan isms that are re peat edly ex -posed to antimi cro bial agents. It is widely ac knowl edged thatanti- microbial re sis tance is spawned in large part by the se -lec tive pres sures of an ti bi otic use and abuse (1,18,19). Thedis cov ery, over use and de vel op ment of re sis tance to new an -ti mi cro bi als is a pre dict able pat tern. World wide us age of an ti -mi cro bi als is stag ger ing. In 1990 in the United Statesan ti bi ot ics were the most com monly pre scribed cate gory ofdrugs, and the sales of an ti bi ot ics to drug stores and hos pi talshave amounted to over $5 bil lion an nu ally since 1991. In thirdworld coun tries where an ti mi cro bi als are avail able over thecoun ter, there is a great pro pen sity for the de vel op ment andspread of re sis tance in the set ting of a huge bur den of in fec -tious dis eases, with poor sani ta tion, over crowd ing and in ap -pro pri ate us age. An ex pand ing popu la tion of very old andvery young in di vidu als who may be par ticu larly sus cep ti ble toin fec tious dis eases, a grow ing popu la tion of in di vidu als withim mu no de fi ciency (AIDS), im mu no sup pres sion (can cer che -mo ther apy, trans plan ta tion), so cie tal be hav ioural changes(pub lic de mand for an ti mi cro bi als, in creased use of day care,sex ual prom is cu ity) and tech no logi cal ad vances are all con -trib ut ing fac tors to the spread of AROs. The con tri bu tion of an -ti mi cro bial us age in ag ri cul ture has been specu lated asan other fac tor con trib ut ing to the de vel op ment and spread ofAROs, but it is proba bly mi nor in com pari son with hu man an ti -mi cro bial us age (20).

The spread of AROs is a com plex and dy namic pro cess and we do not fully un der stand the com plexi ties of this spread.Through out the world, there may be high rates of AROs withinone re gion or coun try and lit tle to no re sis tance in ad join ing re -gions or coun tries. For ex am ple, Por tu gal is rela tively freefrom penicillin- resistant pneu mo cocci whereas Spain hasrates ex ceed ing 50% (21). Simi larly the United States hasma jor prob lems with methicillin- resistant S au reus,vancomycin- resistant en te ro cocci, multidrug- resistant M tu -ber cu lo sis and penicillin- resistant pneu mo cocci, whereas inCan ada there is very lit tle re sis tance to any of these or gan -isms. A col la tion of re gional data (per sonal com mu ni ca tion)

sug gests that the fre quency of iso la tion of methicillin- resistant S au reus is less than 2%, iso la tion of vancomycin- resistanten te ro cocci is ex traor di nar ily rare (22) and high level re sis -tance to S pneu mo niae is re ported as 1.9% in a na tion widesur vey (23).

The rea sons for these dif fer ences are un clear, but an ti bi -otic con trol, con sid ered a cor ner stone of deal ing with mul tire -sis tant or gan isms (1,24,25), par ticu larly in the hos pi tal set ting may of fer some ex pla na tion. Sur veys of hos pi tal phar ma ciesin Can ada and the United States in di cate that 75% of Ca na -dian but only 34% of Ameri can hos pi tal for mu lar ies used pre -scrib ing re stric tions (per sonal com mu ni ca tion, 26). Theremay also be dif fer ences in in fec tion con trol prac tices and fun -da men tal dif fer ences in the de liv ery and ac cess to health care that could also of fer an ex pla na tion for the dif fer ences. What -ever the rea sons there should be no com pla cency with re -spect to AROs in Can ada given the ca pa bil ity formi cro or gan isms to adapt to their sur round ings.

The ap proaches to con trol ling the de vel op ment andspread of AROs have been out lined in sev eral docu ments andre ports (3,4,24,27- 29) in clud ing the Lac Trem blant Dec la ra -tion of The Ca na dian Ex pert Work ing Group on Emerg ing In -fec tious Dis ease Is sues (30). In gen eral, the rec om mendedstrate gies in clude sur veil lance for AROs, im proved an ti mi cro -bial us age in clud ing an ti bi otic re stric tion when ap pro pri ate,re duced en vi ron mental con tami na tion and im prov ing theprac tices of in fec tion con trol to re duce po ten tial cross- transmission of mi cro or gan isms. The prac tice of sound in fec -tion con trol tech niques need not be ap plied only to the in sti tu -tional set ting – day ca res, hos pices and other set tings shouldalso be in cluded. Al though in Can ada, com pared with othercoun tries, AROs do not ap pear to be com mon place at thistime, meas ures to achieve the nec es sary evo lu tion ary bal -ances be tween mi crobe and an ti mi cro bial can, we hope, beachieved with ap pro pri ate pre ven tive ac tion.

REF ER ENCES1. Kunin CM. Perspective: resistance to antimicrobial drugs – A

world-wide calamity. Ann Intern Med 1993;118:557-61.2. Kain K. Emerging pathogens: the birth of plagues. Ann RCPSC

1995;28:141-5.3. Centers for Disease Control and Prevention. Addressing

emerging infectious disease threats: a prevention strategy forthe United States (Executive Summary). MMWR 1994;43(NoRR-5):1-18.

4. Institute of Medicine. Emerging infectious-microbial threats tohealth in the United States. Washington: National AcademyPress, 1992.

5. Begley S. The end of antibiotics. Newsweek 1994;March28:47-9.

6. Noble WC, Virani Z, Cree RGA. Co-transfer of vancomycin andother resistance genes from Enterococcus faecalis NCTC 12201 to Staphylococcus aureus. FEMS Microbiol Lett 1992;72:195-8.

7. Casellas JM, Blanco MG, Eugenia M. The sleeping giant –antimicrobial resistance. Infect Dis Clin North Am 1994;8:29-44.

8. Bloom BR, Murray CJL. Tuberculosis: commentary on are-emergent killer. Science 1992;257:1055-64.

9. Frieden TR, Sterling T, Pablos-Mendez A, Kilburn JO, CauthenGM, Dooley SW. The emergence of drug-resistant tuberculosisin New York City. N Engl J Med 1993;328:521-6.

10. Blumberg HM, Rimland D, Carroll DJ, Terry P, Wachsmuth IK.


CAN J INFECT DIS VOL 6 NO 3 MAY/JUNE 1995 131

Rapid development of ciprofloxacin resistance inmethicillin-susceptible and -resistant Staphylococcus aureus. JInfect Dis 1991;163:1279-85.

11. Leclerq R, Derlot E, Dewal J, Courvalin P. Plasmid-mediatedresistance to vancomycin and teichoplanin in Enterococcusfaecium. N Engl J Med 1988;319:157-61.

12. Reichler MR, Allphin AA, Breiman RF, et al. The spread ofmultiply resistant Streptococcus pneumoniae at a daycarecenter in Ohio. J Infect Dis 1992;166:1346-53.

13. Marton A, Gulyas M, Muoz R, Tomasz A. Extremely highincidence of antibiotic-resistance in clinical isolates ofStreptococcus pneumoniae in Hungary. J Infect Dis1991;163:542-8.

14. Tauxe RV, Puhr ND, Wells JG, Hargrett-Bean N, Blake PA.Antimicrobial resistance of shigella isolates in the USA: theimportance of international travelers. J Infect Dis1990;162:1107-11.

15. Mourad AS, Metwally M, Nour EL, et al. Multiple-drug- resistantSalmonella typhi. Clin Infect Dis 1993;17:135-6.

16. Burwen DR, Banerjee SN, Gaynes RP, and the NationalNosocomial Infections Surveillance System. Ceftazidimeresistance among selected nosocomial gram-negative bacilli inthe United States. J Infect Dis 1994;170:1622-5.

17. Shalit I, Dan M, Gutman R, Gorea A, Berger SA. Crossresistance to ciprofloxacin and other antimicrobial agents among clinical isolates of Acinetobacter calcoaceticus biovar anitratus.Antimicrob Agents Chemother 1990;34:494-5.

18. Cohen ML. Epidemiology of drug-resistance: implications for apost-antimicrobial era. Science 1992;257:1050-4.

19. O’Brien T. Global surveillance of antibiotic resistance. N Engl J Med 1992;329:339-40.

20. Kayeer FH. Evolution of resistance in microorganisms of humanorigin. Vet Microbiol 1993;35:257-67.

21. Otis CL, Monoz TJ, Sala IS. Antibiotic susceptibility of

Streptococcus pneumoniae isolates from paediatric patients. JAntimicrob Chemother 1988;22:659-65.

22. Low DE, Willey BM, McGeer AJ. The threat of the emergence ofantimicrobial-resistant Gram-positive pathogens in Canada. Can J Infect Dis 1994;5(Suppl C): 9C-14C.

23. Low DE, McGeer A and the Canadian Bacterial SurveillanceNetwork. Streptococcus pneumoniae. Canadian BacterialSurveillance Network Newsletter 1995;April:2-3.

24. Marr JJ, Moffet HL, Kunin CM. Guidelines for improving the useof antimicrobial agents in hospitals: a statement by theInfectious Disease Society of America. J Infect Dis1988;157:869-76.

25. Murray BE. Can antibiotic resistance be controlled? N Engl J Med 1994;330:1229-30.

26. Crawford SY, Myers CE. ASHP national survey of hospital-based pharmaceutical services, 1992. Am J Hosp Pharm1993;50:1371-404.

27. Tomasz A. Multiple-antibiotic-resistant pathogenic bacteria – areport on the Rockefeller University Workshop. N Engl J Med1994;330:1247-51.

28. McGowan JE. Antibiotic-resistant bacteria and healthcaresystem: four steps for effective response. Infect Control HospEpidemiol 1995;16:67-70.

29. Cassell GH. ASM Task Force urges broad program onantimicrobial resistance. ASM News 1995;61:116-20.

30. Expert Working Groups on Emerging Infectious Disease Issues.Lac Tremblant Declaration. Can Commun Dis Rep1994;2052:1-19.

JM Conly MD FRCPC

To ronto, On tarioSD Sha fran MD FRCPC

Ed mon ton, Al berta


132 CAN J INFECT DIS VOL 6 NO 3 MAY/JUNE 1995

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