Administrative Office
St. Joseph's Hospital Site, L301-10
50 Charlton Avenue East
HAMILTON, Ontario, CANADA L8N 4A6
PHONE: (905) 521-6141
FAX: (905) 521-6142
http://www.fhs.mcmaster.ca/hrlmp/
Issue No. 37
QUARTERLY NEWSLETTER
June, 1994
THE PROBLEM OF ANTIMICROBIAL RESISTANCE
In the preantibiotic era, infections were the leading cause of hospital admission and mortality in almost all
age groups. With the introduction of the sulfonamides in the 1930's and penicillin in the 1940's, it appeared
that modern medicine had conquered the infectious diseases. However, within three years of clinical use of
penicillin, reports appeared of penicillin resistance in strains of Staphylococcus aureus. History has shown
that this is a repeating pattern; as each new drug is introduced, it is almost always followed by bacterial
resistance.
Bacterial mechanisms to counteract antibiotics can be divided into four main categories:
1.
2.
3.
4.
changes in cell wall permeability to prevent influx of the compound;
production of pumps to expel the drug from the cell;
production of enzymes to inactivate or destroy antibiotics;
changes in the target site.
Highly resistant organisms may employ any combination of these mechanisms. For example, the gene for
resistance to methicillin and cloxacillin in Methicillin-Resistant Staphylococcus aureus (MRSA) is called
mecA. These drugs work by binding to components of the bacterial cell wall called Penicillin-binding Proteins
(PBPs) thus interfering with growth of the cell wall and eventually resulting in cell death. MecA encodes for
an altered PBP so the antibiotics can no longer bind to their target site. This gene can be associated with
genes encoding resistance for other antibiotics such as tetracycline and aminoglycosides, through quite
different mechanisms.
Where do these resistance genes come from? In some cases, they are part of the original or wild type
genome or arise from chromosomal mutations in genes encoding for essential structural or metabolic
enzymes. Bacteria may also acquire new genetic material both within and between species by three
mechanisms: transformation in which genetic material is transferred from the host cell to the recipient;
transduction where fragments of DNA are transported by a bacteriophage into the recipient bacterium; and
conjugation where DNA is transmitted through a specialized cellular appendage. The genetic material which
is exchanged may be extrachromosomal in the form of plasmids or may be specialized segments of
chromosomal DNA called transposons which have sticky ends that facilitate incorporation into the recipient
cell's genome. In some cases, the resistance genes have been traced back to organisms which naturally
produce antibiotics such as Streptomyces, the original source of Streptomycin. It makes sense for these
organisms to have a means of protecting themselves against their own life-threatening products.
Selection pressure for the development of antibiotic resistance is generated not only by antibiotic use in
man but also in veterinary medicine and agriculture where antimicrobials are often used to promote growth.
Ampicillin resistance in Salmonella has been traced back to chicken feed where the drug is routinely added
to encourage weight gain in poultry. Every time we use antibiotics in human or animal subjects,
subtherapeutic concentrations of the drug are found in certain sites, e.g. the skin. Organisms that colonize
these sites are selected for resistance and become reservoirs for resistance genes that may be transmitted
to pathogens at other sites.
Examples of resistance in the community. Antibiotic-resistant bacteria are not a purely hospital-based
problem. In the 1980's, the pattern of MRSA infections was one of nosocomial outbreaks, particularly
amongst burn and intensive care units. However, as some of those patients survived, became colonized and
were discharged back into the community, the pattern of MRSA in Hamilton today shows a mixture of
hospital- and community-acquired infections. Penicillin resistance in pneumococci is predominantly seen in
community-acquired isolates. In the last six months at St. Joseph's Hospital, we have seen two lifethreatening pneumococcal infections, a bacteraemia and a meningitis, where the MICs are only in the
moderately susceptible range. In clinical terms, this translates into a setting where even high-dose penicillin
therapy is likely to fail. One microbiologist in Toronto is finding up to 10% of his pneumococcal isolates are
resistant to penicillin. This was virtually unheard of in North America ten years ago.
Will there always be an alternative antibiotic? There is a prevailing sense of complacency that there will
always be newer and better drugs to combat bacterial infections. From the 1950's to the 1980's, the
pharmaceutical industry devoted vast resources to antimicrobial development but as the market became
glutted, attention was focused to newer and greener pastures. In the past decade, only one new class of
antibiotics was introduced, namely the quinolones. At present, no new classes are on the horizon. The
experience with Ciprofloxacin is a chastening one. When first released, it was touted as the solution to
bacterial resistance. Indeed, it was effective in clearing MRSA from colonized individuals as well as treating
MRSA infections. At the Henderson Hospital in 1988, 100% of Pseudomonas aeruginosa isolates and
more than 90% of Staphylococcus epidermidis isolates were sensitive to Ciprofloxacin. By 1993,
sensitivity rates were down to 80% and 60% respectively. When only ICU isolates are assessed, only 60%
of Pseudomonas aeruginosa isolates were sensitive in 1993.
Controlling the development of resistance. Antibiotic resistance in bacteria is a problem that is here to
stay. Unchecked, it leads to morbidity and mortality in our patients and rising health care costs due to the
need to use more expensive drugs, prolonged courses of these drugs and prolonged hospital stays. The
most important thing we can do to minimize the development of bacterial resistance is to use antibiotics only
when clearly clinically indicated and only for the correct duration. Strategies should also include abandoning
indiscriminate use of antibiotics in agriculture and animal husbandry, and employment of good hygiene and
isolation practices. Preventing antibiotic resistance is a responsibility everyone shares.
E.R. Jeans, MD, FRCPC
We are looking forward to providing further improvements in service, and welcome comments and enquiries.
Feel free to phone us at 521-5084, or 521-2100, extension 3710.
*********************
The Hamilton Health Sciences Laboratory Program is a collaborative program of Hamilton Civic, St.
Joseph's and Chedoke-McMaster Hospitals, which operate Community Laboratory Services as a service to
Hamilton Physicians and their patients.
For further information concerning the Laboratory Program call Mr. A.J. Bailey at 572-7575 and for
Community Laboratory Services telephone Mrs. K. Williams at 521-6052.
Ancaster Centre
226 Wilson Street E.
Ancaster, Ontario
Tel: (905) 648-4080
COMMUNITY LABORATORY SERVICES
Collection Centres
Charlton Centre
Dundas Centre
25 Charlton Ave. E.
16 Cross St.
Hamilton, Ontario
Dundas, Ont.
Tel: (905) 521-6052
Tel: (905) 627-3814 or
(905) 627-7190
Carlisle Centre
Concession Centre
1493 Centre Rd.
688 Concession St.
Carlisle, Ontario
Hamilton, Ontario
Tel: (905) 689-0818
Tel: (905) 383-2021
Fennell Centre
836 Fennell Street E
Hamilton, Ontario
Tel: (905) 383-0505 or
(905) 383-9953
George St. Centre
East Hamilton Centre
196 George St.
1463 Main St. East
Hamilton, Ontario
Hamilton, Ontario
Tel: (905) 525-1562
Tel: (905) 549-5004
For Housecalls
First Place Centre
North Hamilton Centre Stoney Creek Centre
throughout the region,
350 King St. E., Ste. 103 554 John St. North
2757 King Street E.
telephone Mrs. K.
Hamilton, Ontario
Hamilton, Ontario
Hamilton, Ontario
Williams at (905) 521Tel: (905) 522-8765/66
Tel: (905) 522-4197
Tel: (905) 573-4824
6052
For Laboratory Reference Centre Services phone Mrs. B. Baltzer at (905) 521-6065 or fax requests for
information to (905) 528-1464