Antibiotic Resistance in Streptococcus pneumoniae: What Does the Future Hold?

Nuermberger, Eric L.; Bishai, William R.

doi:10.1086/382696

Cited by 45 publications

(38 citation statements)

References 54 publications

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“…Serotype 3 is an important cause of adult pneumococcal disease that is not represented in the PPS-based conjugate vaccine presently used for children (32,33). Hence, antibody-based approaches to treatment of serotype 3 infections may be needed as an adjunct to present therapies in light of the continuing problem of pneumococcal drug resistance and the phenomenon of serotype replacement in PPS-vaccinated children (39,50). The treatment of resistant pneumococcal strains is an area of critical need.…”

Section: Discussionmentioning

confidence: 99%

A Human Monoclonal Immunoglobulin M Reduces Bacteremia and Inflammation in a Mouse Model of Systemic Pneumococcal Infection

Fabrizio

Groner

Boes

et al. 2007

Clin Vaccine Immunol

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Antibody-based approaches to pneumococcal disease may hold promise for immunocompromised patients in whom vaccines are less immunogenic and/or in the context of antimicrobial resistance. Antibody-mediated protection against experimental pneumococcal pneumonia has been shown to depend on immunoregulation, but the relationship between antibody and protection against pneumococcal sepsis and immunoregulation has not been examined. Similarly, the requirement for B and T cells for antibody efficacy is not known. In this study, we determined the efficacy of the human pneumococcal capsular polysaccharide serotype 3-specific, and SCID mice and investigated its effect on cytokine and chemokine expression in sera and spleens from mice with intact cellular immunity. A7 is known to be protective against systemic infection with serotype 3 and to require complement for efficacy. Compared to that of an isotype control antibody, A7 administration prolonged the survival of mice of each immunodeficient strain and was associated with a significant reduction in CFU in blood, lung, and spleen samples and a significantly reduced level of keratinocyte-derived chemokine (KC), interleukin-6 (IL-6), and macrophage inflammatory protein-2 (MIP-2) expression in normal and sIgM ؊/؊ mice. Studies with mice treated with penicillin revealed similar reductions in CFU and similar levels of IL-6, KC, or MIP-2 expression in A7-and penicillin-treated mice. These findings demonstrate that natural IgM and B and T cells are dispensable for A7-mediated protection against experimental pneumococcal sepsis and suggest that the efficacy of antibody-mediated protection depends on immunomodulation. Taken together, our data extend the association between antibody-mediated protection and immunomodulation to protection against systemic pneumococcal infection and to a clinically important serotype often responsible for pneumococcal sepsis.

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Section: Discussionmentioning

confidence: 99%

A Human Monoclonal Immunoglobulin M Reduces Bacteremia and Inflammation in a Mouse Model of Systemic Pneumococcal Infection

Fabrizio

Groner

Boes

et al. 2007

Clin Vaccine Immunol

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“…Antimicrobial resistance can be associated with a decrease in bacterial fitness (3,27). A measure of fitness of antimicrobial-resistant pathogens could aid in the prediction of the future rates of disease caused by these bacteria, guide recommendations for empiric therapy for some bacterial infections, and direct the development of new antimicrobial drugs.…”

Section: Discussionmentioning

confidence: 99%

Relative Fitness of Fluoroquinolone-resistantStreptococcus pneumoniae

Johnson

Briles

Benjamin

et al. 2005

Emerg. Infect. Dis.

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Fluoroquinolone resistance in Streptococcus pneumoniae is primarily mediated by point mutations in the quinolone resistance–determining regions of gyrA and parC . Antimicrobial resistance mutations in housekeeping genes often decrease fitness of microorganisms. To investigate the fitness of quinolone-resistant S. pneumoniae (QRSP), the relative growth efficiencies of 2 isogenic QRSP double mutants were compared with that of their fluoroquinolone-susceptible parent, EF3030, by using murine nasopharyngeal colonization and pneumonia models. Strains containing the GyrA: Ser81Phe, ParC: Ser79Phe double mutations, which are frequently seen in clinical QRSP, competed poorly with EF3030 in competitive colonization or competitive lung infections. However, they efficiently produced lung infection even in the absence of EF3030. The strain containing the GyrA: Ser81Phe, ParC: Ser79Tyr double mutations, which is seen more frequently in laboratory-derived QRSP than in clinical QRSP, demonstrated reduced nasal colonization in competitive or noncompetitive lung infections. However, the strain was equally able to cause competitive or noncompetitive lung infections as well as EF3030.

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“…Because nasopharyngeal colonization is the key event leading to cross-transmission on one hand and infection on the other (15,20), it appears to be extremely important to analyze the factors responsible for S. pneumoniae transmission in the population, like the impact of resistance described below. These factors also include high antigenic diversity, with about 90 serotypes described to date, and the effects of public health measures, e.g., the introduction of the pneumococcal conjugate vaccine and policies restricting antibiotic use applied in some countries, including France.…”

mentioning

confidence: 99%

Intrinsic Epidemicity of Streptococcus pneumoniae Depends on Strain Serotype and Antibiotic Susceptibility Pattern

Cellès

Opatowski

Salomon

et al. 2011

Antimicrob Agents Chemother

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Streptococcus pneumoniae is a major cause of invasive diseases worldwide. It spreads through an interindividual transmission, followed by usually harmless colonization of the host. Possible transmission differences reflecting intrinsic strain features (e.g., serotype and antibiotic susceptibility) have been little studied so far. In this study, we used epidemiological data from an interventional trial of S. pneumoniae carriage among kindergartners and developed a mathematical model to estimate the transmission parameters of the different strains isolated during that study. We found small but significant transmissibility differences between the observed serotypes: serotypes 3, 6A, and 19A were found to be the most epidemic, while serotypes 23F, 9V, and 14 were the least epidemic. Further analysis indicated that, within a serotype, susceptible and resistant strains had different abilities to be transmitted. Susceptible-to-resistant transmission rate ratios were computed for five serotypes; susceptible strains were significantly more epidemic than resistant strains for serotypes 6A (mean, 1.02) and 19F (1.05). Serotype 19A resistant strains were not outcompeted by susceptible strains (0.97). Nonsignificant trends were observed for serotypes 6B (1.01) and 15A (0.98). Our results support the existence of heterogeneous abilities of the different serotypes for host-to-host transmission. They also suggest that antibiotic susceptibility within a serotype affects this transmissibility. We conclude that pneumococcal strains should not be considered equally at-risk in terms of transmission. Further quantification of strain-specific epidemic potential is needed, especially in a context of extensive use of conjugate vaccines with the aim of preventing pneumococcal infections.

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Antibiotic Resistance in Streptococcus pneumoniae: What Does the Future Hold?

Cited by 45 publications

References 54 publications

A Human Monoclonal Immunoglobulin M Reduces Bacteremia and Inflammation in a Mouse Model of Systemic Pneumococcal Infection

A Human Monoclonal Immunoglobulin M Reduces Bacteremia and Inflammation in a Mouse Model of Systemic Pneumococcal Infection

Relative Fitness of Fluoroquinolone-resistantStreptococcus pneumoniae

Intrinsic Epidemicity of Streptococcus pneumoniae Depends on Strain Serotype and Antibiotic Susceptibility Pattern

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