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Previous Article | Next Article 
Journal of Clinical Microbiology, February 2001, p. 733-737, Vol. 39, No. 2
Institut National de Santé Publique du
Québec-Laboratoire de Santé Publique du Québec,
Sainte-Anne-de-Bellevue, Quebec H9X 3R5,1
Unité de Maladies Infectieuses, Régie
Régionale de la Santé et des Services Sociaux de
Montréal-Centre, Montreal, Quebec H2L
1M3,2 Faculté de Médecine,
Université de Sherbrooke, Sherbrooke, Quebec J1H
5N4,3 Centre Hospitalier
Universitaire de Montréal, L'Hôpital Saint-Luc, Montreal,
Quebec H2X 3J4,4 and McGill
University Health Centre, Royal Victoria Hospital, Montreal, Quebec H3A
1A1,5 Canada
Received 21 July 2000/Returned for modification 28 September
2000/Accepted 5 November 2000
In the province of Quebec, Canada, from 1996 to 1998, 3,650 invasive Streptococcus pneumoniae infections were reported.
A total of 1,354 isolates were serotyped and tested for antimicrobial susceptibility. The distribution of serotypes remained stable over the
3 years, with serotypes 14, 6B, 4, 9V, 23F, and 19F accounting for 61%
of the isolates. Overall, 90% of isolates were included in the current
23-valent vaccine and 67% were included in the 7-valent conjugate
vaccine. We were able to determine that resistance to penicillin and to
other antibiotics is increasing.
Streptococcus pneumoniae
is a significant bacterial pathogen causing pneumonia, meningitis,
otitis media, and bacteremia (17). There is a worldwide
increase in the incidence of pneumococcal resistance to several
antimicrobial agents (3, 9, 15, 16, 18, 33). In some areas
of the United States, as many as 35% of invasive isolates have been
reported to be nonsusceptible to penicillin (5, 6). In
Canada, prior to 1990, the rates of
penicillin resistance were less than 5%
(1, 8, 13, 19, 23). During the last decade, reports from
Canada have identified increasing rates of nonsusceptibility to
penicillin, ranging from 7.8 to 20% for invasive isolates (21,
32). In Quebec, resistant strains, especially those of serotype
23F, as well as multiresistant strains have been identified
(14). The Laboratoire de Santé Publique du
Québec (LSPQ) initiated, in November 1995, a surveillance program
in order to monitor the invasive pneumococcal infections in Quebec and
to provide the Ministry of Health with data to be used in establishing
pneumococcal vaccination policies. In this article, we report the data
obtained from 1996 to 1998.
Since the beginning of this surveillance program, all hospital
laboratories (134 in 1996 to 114 in 1998) have reported on a monthly
basis the total number of S. pneumoniae strains isolated from normally sterile body fluids, using a questionnaire sent to the
LSPQ. The total population of the province of Quebec was estimated at
7,396,742 people in 1996 (28). The surveillance case
definition was the isolation of S. pneumoniae in a normally sterile body fluid such as blood or cerebrospinal fluid from patients of any age (one isolate per patient per 14-day period). Twenty-seven hospitals, located throughout major regions of the province and cities,
were enrolled as sentinel units and asked to send all of their
invasive pneumococcal isolates to the LSPQ. Identification of isolates
was confirmed by colony morphology, susceptibility to
ethylhydrocuprein, and agglutination with antipneumococcal polysaccharide capsule antibodies by a Quellung reaction
(22). Serotyping was performed by the capsular swelling
method (22) using antisera from Statens Seruminstitut,
Copenhagen, Denmark, in collaboration with Marguerite Lovgreen,
National Center for Streptococcus, University of Alberta, Edmonton,
Canada. Testing of susceptibility to penicillin G, ceftriaxone and
ofloxacin was performed by using the broth microdilution method, and
testing of susceptibility to chloramphenicol, erythromycin,
rifampin, trimethoprim-sulfamethoxazole (TMP-SMX), and vancomycin
was performed by the agar dilution method during the first half of the
study and by broth microdilution thereafter. Both methods were
performed in accordance with those of the National Committee for
Clinical Laboratory Standards (25, 26). Antibiotic powders
were purchased from Sigma Chemical Co., St. Louis, Mo. We defined
reduced susceptibility as including intermediate and resistant
categories and multiple resistance as including reduced susceptibility
to three or more classes of antimicrobial agents. Information on age,
sex, type of infection, and clinical outcome for each patient at the
time the isolate was shipped to the LSPQ was provided by each sentinel unit. Statistical analysis of the data was performed by the chi-square test (34). A P value of <0.05 was considered
statistically significant.
During the 3-year period of this study, a total of 3,650 cases of
invasive S. pneumoniae infection were reported, for a mean incidence of 16.5 per 100,000 persons annually (15.5 during 1996, 17.3 during 1997, and 16.6 during 1998). Although the total number of cases
remained stable over these years (1996, 1,139; 1997, 1,280; 1998, 1,231), the distribution was seasonal, reflecting the influence, during
the winter, of the respiratory viral infection season on the risk of
acquiring pneumococcal pneumonia.
A total of 1,354 isolates representing 37% of all reported
isolates were received at the LSPQ (450 during 1996, 434 during 1997, and 470 during 1998) for analysis. Strains were isolated from
blood (93.4%), cerebrospinal fluid (4.1%), or other normally sterile
sites (2.5%). Table 1 shows the
distribution of the serotypes by age. Overall, 90% of the isolates
(1,217 of 1,354) were included in the current 23-valent vaccine and
67% (904 of 1,354) were included in the new 7-valent conjugate
vaccine.
0095-1137/01/$04.00+0 DOI: 10.1128/JCM.39.2.733-737.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Surveillance of Invasive Streptococcus pneumoniae
Infection in the Province of Quebec, Canada, from 1996 to 1998:
Serotype Distribution, Antimicrobial Susceptibility, and Clinical
Characteristics
ABSTRACT
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TABLE 1.
Distribution of serotypes with respect to the age of the
patient and serotype inclusion in the 23-valent vaccine or in the
7-valent conjugated vaccine
Globally, 25% (342 of 1,354) of the isolates were nonsusceptible to
one or more of the antimicrobial agents studied. Table 2 shows the percentage of isolates with
reduced susceptibility to each antibiotic tested over the 3 years. Globally, nonsusceptibilities to penicillin, ceftriaxone,
chloramphenicol, erythromycin, and TMP-SMX were 11.7, 7.7, 2.7, 8.1, and 20.2%, respectively. Nine isolates were found to be
nonsusceptible to ofloxacin during 1998, including eight intermediate
isolates (MICs of 4 µg/ml). One isolate showing an ofloxacin MIC of
16 µg/ml was also intermediate to penicillin and resistant to
TMP-SMX. All isolates were susceptible to vancomycin. The serotypes of
the 158 penicillin-nonsusceptible isolates were those commonly
associated with penicillin resistance: 9V (55 isolates), 14 (30 isolates), 23F (27 isolates), 6B (19 isolates), 19A (9 isolates), 6A (9 isolates), 19F (6 isolates), 17F (2 isolates), and 35B (one isolate),
with the last being the only one not included in the 23-valent vaccine.
Among the 36 penicillin-nonsusceptible isolates recovered from patients
under 2 years old, 34 (94%) were included in the 7-valent conjugate
vaccine. Among the 79 meningitis cases, five and six isolates were
intermediate and resistant to penicillin, respectively, and six
isolates were intermediate to ceftriaxone (MIC of 1 µg/ml). There
were nine fatal cases of meningitis, all caused by strains susceptible
to both antibiotics. During 1998, we observed that the proportion of
penicillin-nonsusceptible isolates was significantly higher for
patients under 2 years of age than for older patients (25.3 versus
11.2%) (P < 0.01). Also, the proportion of
nonsusceptible isolates among young children was found to increase over
the years from 7.9 to 25.3% (P < 0.005, chi-square for
trend). Multiple resistance patterns were observed in 56 of the 1,354 isolates (4.1%). The isolates were resistant to 
-lactams (except
for four isolates) and to at least two of the following agents:
erythromycin, chloramphenicol, TMP-SMX, and ofloxacin.
|
The types of infection and the clinical outcomes with respect to
serotypes in both pediatric and adult groups are shown in Fig.
1 and 2. In
pediatric patients, bacteremia without a primary focus of infection was
most frequent (42%), while pneumonia was predominant (61.5%) in
adults. The overall mortality rate was 7.2% (97 of 1,354 patients).
This fatality rate, which is lower than the 12% reported in the United
States (10), could be explained partly by the fact that
the present study used clinical information that was available at the
time the isolates were sent to the LSPQ by the sentinel units. Thus,
the mortality rate does not include those patients who may have died
after the clinical information and isolates were forwarded. However,
the mortality rate increased in relation to age, with a rate of 1.3%
(5 of 388) in patients under 18 years of age (including 4 under 2 years
of age), 7.4% (34 of 458) in patients between 18 and 64 years old, and
11.4% (58 of 508) in those 
65 years old (P < 0.05).
|
|
The observed mean incidence rate is lower than that of 24.1/100,000 reported among persons of all ages in the United States during 1998 by the Centers for Disease Control and Prevention (Active Bacterial Core Surveillance Report [http://www.cdc.gov/ncidod/dbmd/abcs]) but is consistent with a rate of 14.7/100,000 reported in metropolitan Toronto and the Peel region in 1995 (J. D Kellner et al., Abstr. 38th Intersci. Conf. Antimicrob. Agents Chemother., abstr. L-44, 1998).
As observed a decade ago in Quebec (13) and in other parts of Canada (21), the serotype coverage of the 23-valent vaccine remains at least 90% for adult patients and those aged 2 to 18 years. In the event that the 7-valent conjugate vaccine (29, 31) is licensed for use in Canada, 90% of infections occurring among children <2 years of age could potentially be prevented by immunization. Considering that the conjugate 7-valent vaccine has been licensed in the United States for use in children under 10 years of age, 87.2% of cases in this age group would be preventable. If the recommendations were to vaccinate younger children under 5 years of age, 88% of cases would then be preventable.
Since our last report (13), the prevalence of isolates with reduced susceptibility to penicillin increased dramatically, from 1.6% (6 of 468 isolates) to 11.7% (158 of 1 354 isolates). Ten years ago, no fully penicillin-resistant isolates were found, while this study identified 7.0% of such strains. This increase in the number of isolates showing reduced susceptibility to penicillin is consistent with observations in Canada (20, 21, 30) and worldwide (2, 9, 12, 16, 18, 33). The most frequent serotype among penicillin-nonsusceptible isolates was serotype 9V, accounting for 35% of such isolates. A study conducted in Canada from 1991 to 1998 (D. Greenberg et al., Abstr. 39th Intersci. Conf. Antimicrob. Agents Chemother., abstr. 1030, 1999) concluded that this serotype appeared in Quebec, spreading to Ontario, Alberta, and British Columbia and was related to a Spanish-French clone (20, 24). As reported elsewhere (21, 27, 35), erythromycin resistance has also increased in Quebec, from 0.4% during 1984 to 1986 (13) to 4.9% in 1996 and 10% in 1998 (P < 0.05). The high proportion of isolates with reduced susceptibility to TMP-SMX observed is consistent with Canadian surveys reporting rates of 18.5% (32) and 19.5% (21). The ofloxacin nonsusceptibility rate is similar to that in other Canadian studies reporting <2.0% of strains as nonsusceptible to fluoroquinolones (J. A. Karlowsky, G. G. Zhanel, and D. J. Hoban, Abstr. 39th Intersci. Conf. Antimicrob. Agents Chemother., abstr. 822, 1999) (7), confirming that resistance to fluoroquinolones is very low in Quebec.
We observed a mortality rate of 11.4% in the elderly, confirming that age by itself is one of the most important factors associated with fatal pneumococcal pneumonia (4, 11, 13).
This study has shown that the formulation of the current 23-valent vaccine and the recently licensed 7-valent conjugate vaccine will cover the great majority of isolates implicated in the respective target groups, supporting the use of vaccination programs as a means to prevent pneumococcal infection.
Since the fall of 1999, in the province of Quebec, the Ministry of Health has funded a vaccination program for persons 2 years old and older with risk factors for severe pneumococcal infections. This program will be extended to the elderly (65 years and older) during the fall of 2000. The implementation of an immunization program with the 7-valent conjugate vaccine must await its licensing for use in Canada.
Our continuing surveillance program will enable us to monitor the impact of new publicly funded antipneumococcal vaccination programs in Quebec.
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ACKNOWLEDGMENTS |
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We acknowledge Stéphane Charbonneau, Lucie Cormier, Martial Demers, Robert Langevin, and François Robillard for their technical assistance. We are grateful to Luc Massicotte for the supervision of medium preparation and to Johanne Lefevbre for identification expertise. We also thank all the technologists in hospital microbiology laboratories who sent us pneumococcal strains. We acknowledge Marguerite Lovgren of the National Centre for Streptococcus, University of Alberta, Edmonton, Canada, for her contribution to the serotyping. Finally, we thank Lucie Carrière for secretarial assistance.
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FOOTNOTES |
|---|
* Corresponding author. Mailing address: INSPQ-Laboratoire de Santé Publique du Québec, 20 045 Chemin Sainte-Marie, Sainte-Anne-de-Bellevue, Quebec H9X 3R5, Canada. Phone: (514) 457-2070. Fax: (514) 457-6346. E-mail: ljette{at}lspq.org.
Pneumococcus Study Group members are as follows: M. Audy, Centre de Santé Tulattavik de I'Ungava, Kuujjuaq, Quebec
JOM 1CO, Canada; J. F. Boisvert, CHAUQ (Pavillon Saint-Sacrement),
Quebec City, Quebec G1S 4L8, Canada; H. Brodeur, Carrefour Santé
du Granit, Lac Mégantic, Quebec G6B 1A5, Canada; J. Caron,
CLSC-Centre Hospitalier et d'Hébergement Memphrémagog,
Magog, Quebec J1X 3X3, Canada; C. Chouinard, CHUM-Hôtel-Dieu,
Montreal, Quebec H2W 1T8, Canada; J. P. Côté, Les
CLSC., C.H. et C.H.L.S.D. de la MRC d'Asbestos, Asbestos, Quebec J1T
1X6, Canada; L. Côté, Centre Hospitalier Universitaire de
Québec-Pavillon CHUL, Quebec City, Quebec G1V 4G2, Canada; M. Cousineau, Centre de Santé Inuulitsivik, Purvinituq, Quebec JOM
1PO, Canada; L. Dion, Centre Universitaire de Santé de I'Estrie
(Site Bowen), Sherbrooke, Québec J1G 2E8, Canada; P. Flamand,
CHUM-Hôpital Notre-Dame, Montreal, Quebec H2L 4M1, Canada; G. Gagnon, Centre Régional S.S.S. de la Baie-James, Radisson, Quebec
JOY 2X0, Canada; C. Gaudreau and P. Turgeon, CHUM-Hôpital
Saint-Luc, Montreal, Quebec H2X 3J4, Canada; S. Landry, Centre
Régional S.S.S. de la Baie-James, Matagami, Quebec JOY 2AO,
Canada; J. R. Lapointe, Hôpital Sainte-Justine, Montreal, Quebec H3T 1C5, Canada; M. Laverdière, Hôpital
Maisonneuve-Rosemont, Montreal, Quebec H1T 2M4, Canada; J. McDonald,
L'Hôpital de Montréal pour Enfants, Montreal, Quebec H3N
1P3, Canada; M. A. Miller, Hôpital Général Juif
S.M.B.D., Montreal, Quebec H3T 1E2, Canada; F. Morin-Coutu, Centre
Universitaire de Santé de I'Estrie (Site King), Sherbrooke,
Quebec J1G 1B1, Canada; A. Paradis, CHAUQ (Pavillon Enfant-Jésus), Quebec City, Quebec G1J 1Z4, Canada; J. F. Paradis, Complexe Hospitalier de la Sagamie (Pavillon St-Vallier),
Chicoutimi, Quebec G7H 5H6, Canada; S. Richard, Conseil Cri SSS de la
Baie James, Chisasibi, Quebec JOM 1EO, Canada; H. G. Robson,
Hôpital Royal Victoria, Montréal, Quebec H3A 1A1, Canada;
C. Sinave, Centre Universitaire de Santé de I'Estrie (Site
Fleurimont), Fleurimont, Quebec J1H 5N4, Canada; M. Soulard, Centre
Régional S.S.S. de la Baie-James, Chibougamau, Quebec G8P 1N1,
Canada; B. Thivierge, Hôpital du Sacré-Coeur de
Montréal, Montreal, Quebec H4J 1C5, Canada; F. Tourangeau, Centre
Hospitalier de Rimouski, Rimouski, Quebec G5L 5T1, Canada; and M. Trousdell, Institut Universitaire de Gériatrie-Sherbrooke
(Pavillon Argyll), Sherbrooke, Quebec J1J 3H5, Canada.
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