Increase in penicillin resistance of invasive Streptococcus pneumoniae in Brazil after 1999

Maria-Cristina C. Brandileone1,*, Silvana Tadeu Casagrande1, Maria-Luiza L. S. Guerra1, Rosemeire Cobo Zanella1, Ana-Lucia S. Sgambatti de Andrade2 and José-Luis Di Fabio3

1 Adolfo Lutz Institute, São Paulo, Brazil; 2 Institute of Tropical Pathology and Public Health, Federal University of Goiás, Goiás, Brazil; 3 Technology and Health Service Delivery, Pan American Health Organization (PAHO), Washington, DC, USA


* Corresponding author. Fax: +55-11-3085-3505; E-mail: brandi{at}ial.sp.gov.br

Keywords: S. pneumoniae , pneumococcal infections , antimicrobial resistance surveillance

Sir,

The emergence and spread of resistance in Streptococcus pneumoniae during recent decades has promoted improvement of the surveillance of S. pneumoniae in order to generate regional data to guide the empirical treatment of infections.1 In 1993, with the introduction of the SIREVA project in Brazil, proposed by the Pan American Health Organization to the Latin American countries,2 monitoring of pneumococcal resistance was initiated in the region.

In Brazil, the Adolfo Lutz Institute (IAL), the public health laboratory for São Paulo state, is the National Reference Centre for pneumococcal infections. The IAL systematically receives invasive pneumococcal isolates from hospitals and regional public health laboratories, dispersed throughout the country, through the network of the national surveillance system coordinated by the Minister of Health of Brazil. Pneumococcal strains isolated from normally sterile fluids of hospitalized patients with community-acquired infections are sent voluntarily to IAL with demographic data for monitoring antimicrobial resistance. We briefly report here the increase in penicillin resistance of invasive pneumococci in Brazil between 1998 and 2003.

At the IAL, the S. pneumoniae isolates were investigated for their penicillin resistance by MIC determination using broth microdilution methodology and interpretative criteria standardized by the Clinical and Laboratory Standards Institute/NCCLS.3 An external Quality Assurance Program coordinated by the National Centre for Streptococcus, Edmonton, Alberta, Canada has validated the performance of testing and the results. All information was recorded using EpiInfo software version 6.04 (Centers for Disease Control and Prevention, Atlanta, GA, USA) and statistical analyses were performed using SSPS software, version 10.0 (SPSS Inc., Chicago, IL, USA). Logistic regression was applied to assess the odds ratio (OR) and respective 95% confidence intervals of the non-susceptible pneumococci (NSP) isolation by year.

Between 1998 and 2003, 3914 pneumococci recovered from meningitis (69.4%), pneumonia (20.6%) or other invasive infections (10%) were studied. Approximately 50% were from children up to 5 years old. No significant differences were found in the frequency of isolates by clinical diagnosis and patient age, or in the criteria for sending isolates to IAL during the period of study.

Over the 6 years of the survey, the frequency of NSP in Brazil was 21.7%, with 17.2% of isolates showing intermediate resistance (IR) (MIC 0.12–1.0 mg/L) and 4.5% showing high resistance (HR) (MIC > 1.0 mg/L). The prevalence of NSP increased from 15.1% in 1998 to 26.8% in 2003. IR and HR rates have increased from 13.2% and 1.9% in 1998, to 19.6% and 7.2% in 2003, respectively (Table 1). A statistically significant increase in the prevalence of penicillin NSP was observed since the year 2000. The estimated risk of having HR isolates was almost four-fold (OR 3.99) higher in 2003 compared with 1998, while the risk for IR isolates was 1.61. Thus, although the frequency of isolates showing IR to penicillin was higher than the frequency of isolates with HR, analysis showed that the risk of detecting HR isolates in 2003 increased by 300% when compared with 1998, while the corresponding risk for IR was lower at 61%.


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Table 1. Percentage of pneumococci non-susceptible to penicillin by year in Brazil

 
Prior to 2000, resistance rates to penicillin in Brazil were lower than those found in other Latin American countries and were gradually increasing at a lower rate through the years.46 However, the present data show the rapid dissemination of penicillin NSP among invasive pneumococci in Brazil after 1999, mainly associated with a high level of resistance. Thus, we record the year 2000 as a transitional period towards a progressive emergence of penicillin NSP, reinforcing the continued national surveillance to promote appropriate antimicrobial use against invasive pneumococcal infection in the region.

Acknowledgements

We are grateful to the Pan American Health Organization (PAHO/WHO), Washington, DC, for providing the Quality Control Program for Antimicrobial Resistance of S. pneumoniae, and the National Centre for Streptococcus, Edmonton, Alberta, Canada, for performing this Quality Control Program. We also thank the National Coordination of the Public Health Laboratories (CGLAB, SVS), Ministry of Health, and the public health laboratories and other institutions in Brazil that have collaborated with the pneumococcal surveillance. This work received financial support from the Brazilian Council for Science and Technology Development (CNPq-Grants Research: 303348/2004-6, 308043/2004-9, 302628/2004-5), the Pan American Health Organization (PAHO), the Canadian International Development Agency (CIDA) and the Instituto Adolfo Lutz (IAL), São Paulo, Brazil.

References

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