Clinical Study
Serotypes, antimicrobial resistance and genotypes of Streptococcus pneumoniae associated with infections in cancer patients in Brazil

https://doi.org/10.1016/j.diagmicrobio.2016.11.017Get rights and content

Highlights

  • Pneumococcal isolates causing diseases in cancer patients were characterized.

  • A large diversity of genotypes and capsular types were detected.

  • Globally disseminated clones associated with resistance were found.

  • Some genotypes seem to have a regional dissemination.

  • Combined vaccination might reduce burden of pneumococcal diseases in such patients.

Abstract

We sought to characterize pneumococcal isolates associated with bacteremia, pneumonia and meningitis in cancer patients and to estimate the coverage of the available pneumococcal vaccines. Fifty isolates recovered from 49 patients attending a cancer reference center over a 1-year period were analyzed. The prevalent serotypes were: 23F (12%), 6A (8%), 3, 4, 20, and 23A (6% each). All isolates were susceptible to chloramphenicol, levofloxacin, rifampicin, and vancomycin. Resistance or reduced susceptibility to penicillin made up 14%, and one isolate was also intermediately resistant to ceftriaxone. The three (6%) erythromycin-resistant isolates presented the M or cMLSB phenotypes and harbored the mef(A/E) gene exclusively or along with the erm(B) gene. Twenty-two (44%) isolates were closely related to 11 international clones, being strongly associated with penicillin non-susceptibility. Combined immunization with the 13-valent conjugate and the 23-valent polysaccharide vaccines might contribute to reduce (76%) the burden of the pneumococcal infections in the population investigated.

Introduction

Pneumonia, bacteremia and meningitis constitute the major clinical syndromes of severe pneumococcal infections. They are strongly associated with a variety of predisposing conditions, particularly pulmonary disease (CDC, 2015). Among the other conditions, decreased immune function plays a significant role in increasing the risk to acquire pneumococcal infections (Wong et al., 2010).

Cancer patients with hematological malignancies and/or solid tumors are more prone to develop bacterial infections, mostly bloodstream infections, and Gram-positive microorganisms are the predominant pathogens among these patients (Bos et al., 2013, Rolston et al., 2013, Wisplinghoff et al., 2004). In patients with untreated multiple myeloma, Streptococcus pneumoniae is a leading cause of infections, particularly pneumonia (Kalambokis et al., 2009). Moreover, an increased risk for invasive pneumococcal diseases has been observed in children with acute lymphoblastic leukemia (Meisel et al., 2007).

Among S. pneumoniae isolates, antimicrobial resistance most often reflects the spread of a few internationally disseminated clones recognized by the Pneumococcal Molecular Epidemiology Network (PMEN; http://www.pneumogen.net/pmen/). These clones are frequently associated with diseases, widely distributed geographically and usually resistant to one or more clinically relevant antibiotics (McGee et al., 2001). Additionally, susceptible pneumococcal clones known to be globally important as causes of disease are also considered by the PMEN.

Despite the availability of studies on the prevalence of pneumococcal infections in cancer patients, little is known about the characteristics of pneumococcal isolates associated with diseases in these patients. Hence, the aim of the present study was to determine the distribution of capsular types, antimicrobial resistance and the population structure of pneumococcal isolates recovered from patients with severe infections admitted to an oncological reference center in Brazil, and to estimate the theoretical coverage of the available pneumococcal vaccines in the population investigated.

Section snippets

Patients and pneumococcal isolates

Fifty pneumococcal isolates from 49 patients with pneumococcal diseases receiving medical assistance at the Instituto Nacional de Câncer (INCA/RJ), Rio de Janeiro, Brazil, from April 2013 to April 2014, were included in the study. In one case, two different isolates were obtained from a single patient 5 months apart. Supplementary file provides the clinical and demographical data of the patients.

The age range of the patients varied from 1 to 87 years old (IQR: 26.5–65 years old), 43 (87.8%) of

Results

All the 50 isolates were α-hemolytic and soluble in the presence of bile salts. Three isolates were resistant to optochin: one isolate was uniformly resistant and the other two presented subpopulations of both optochin susceptible and resistant cells. Only two isolates were negative when tested by the Slidex pneumo-kit®, but confirmed as S. pneumoniae based on typical results in the other tests: α-hemolytic, susceptible to optochin, and soluble in bile salts.

Twenty-seven different capsular

Discussion

Pneumococcal diseases are a global public health concern, particularly in low-and lower-middle-income countries, where epidemiological data are still limited and, when available, the focus is often related to children under 5 years old, considered the major target population for pneumococcal infections. On the other hand, other individuals, including cancer patients, are at high-risk for development of severe pneumococcal diseases and studies focusing on such populations are rare worldwide.

The

Conflicts of Interest

None.

Acknowledgements

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), and Pró-Reitoria de Pesquisa, Pós-Graduação e Inovação da Universidade Federal Fluminense (PROPPi/UFF).

We thank the Plataforma de Sequenciamento de DNA (DNA Sequencing Platform) of the Universidade Federal Fluminense.

References (29)

  • Clinical and Laboratory Standards Institute (CLSI)

    Performance standards for antimicrobial susceptibility testing

  • C.A. Dias et al.

    Diversity of mutations in the atpC gene coding for the c subunit of F0F1ATPase in clinical isolates of optochin-resistant Streptococcus pneumoniae from Brazil

    J Clin Microbiol

    (2007)
  • C.A. Dias et al.

    Sequential multiplex PCR for determining capsular serotypes of pneumococci recovered from Brazilian children

    J Med Microbiol

    (2007)
  • M.C. Enright et al.

    Multilocus sequence typing scheme for Streptococcus pneumoniae: identification of clones associated with serious invasive disease

    Microbiology

    (1998)
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