Antibacterial resistance patterns in Streptococcus pneumoniae isolated from elderly patients: PROTEKT years 1–5 (1999–2004)

Ünal, Serhat; Farrell, David J.

doi:10.1016/j.ijantimicag.2007.07.025

Cited by 9 publications

(9 citation statements)

References 14 publications

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“…The ill effects of primary and secondary pulmonary bacterial infections are increasingly being felt in older populations, with Streptococcus pneumoniae ( S. pne ) being the most causative organism in both immunocompromised and non-immunocompromised populations (7). With the increased emergence of antibiotic strains of S. pne and increased incidence of co-infections, it is imperative to elucidate the mechanisms that underlie age associated impairments in innate immunity and devise therapeutic treatment strategies to augment these responses (8-11). …”

Section: Introductionmentioning

confidence: 99%

Age-Enhanced Endoplasmic Reticulum Stress Contributes to Increased Atg9A Inhibition of STING-Mediated IFN-β Production during Streptococcus pneumoniae Infection

Mitzel

Lowry

Shirali

et al. 2014

The Journal of Immunology

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Pneumococcal infections remain a leading cause of death in persons ≥ 65 years of age. Recent reports have illustrated detrimental changes in the ER stress response or unfolded protein response (UPR) in aging and age-related diseases; however the relationship between aging, the UPR, and innate immune responses to Streptococcus pneumoniae has not been fully elucidated. Our results illustrate that STING mediated production of IFNβ during S. pneumoniae infection is decreased in aged hosts. Enhanced ER stress in response to S. pne umoniae augmented IRE1/XBP1 mediated production of Atg9a. Knockdown of Atg9a or treatment with gemcitabine HCL resulted in enhanced STING mediated production of IFNβ by aged macrophages. Consecutive treatments with gemcitabine during in vivo S. pneumoniae infection decreased morbidity and mortality in aged hosts which was associated with decreased Atg9a expression, increased IFNβ production, and improved bacterial clearance from lung tissue. Taken together, data presented in this study provide new evidence as to why older persons are more susceptible to S. pneumoniae and provide a possible mechanism to enhance these responses, thereby decreasing morbidity and mortality in this population.

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Section: Introductionmentioning

confidence: 99%

Age-Enhanced Endoplasmic Reticulum Stress Contributes to Increased Atg9A Inhibition of STING-Mediated IFN-β Production during Streptococcus pneumoniae Infection

Mitzel

Lowry

Shirali

et al. 2014

The Journal of Immunology

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“…Antimicrobials have been used successfully for the treatment of many infectious diseases; however, the continuous increase in resistance among many bacteria in the community, as well as in the hospital setting, has led to research for new classes of antibiotics with a broader range of activity against pathogenic microorganisms (2,6,17,18). Tigecycline is a novel antibiotic, a 9-t-butylglycylamido derivative of minocyline, which inhibits protein synthesis in the presence of tetracycline-resistant, tet(M)-protected ribosomes (30); it belongs to a new semisynthetic class of antimicrobials named glycylcyclines (37).…”

mentioning

confidence: 99%

Tigecycline Therapy Significantly Reduces the Concentrations of Inflammatory Pulmonary Cytokines and Chemokines in a Murine Model of Mycoplasma pneumoniae Pneumonia

Salvatore¹,

Techasaensiri²,

Tagliabue

et al. 2009

Antimicrob Agents Chemother

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Antimicrobials have been used successfully for the treatment of many infectious diseases; however, the continuous increase in resistance among many bacteria in the community, as well as in the hospital setting, has led to research for new classes of antibiotics with a broader range of activity against pathogenic microorganisms (2,6,17,18). Tigecycline is a novel antibiotic, a 9-t-butylglycylamido derivative of minocyline, which inhibits protein synthesis in the presence of tetracycline-resistant, tet(M)-protected ribosomes (30); it belongs to a new semisynthetic class of antimicrobials named glycylcyclines (37). It has been shown to have activity against a wide range of microorganisms, both gram-positive and gram-negative bacteria, as well as anaerobes (16,29,39). Moreover tigecycline has activity in vitro against rapidly growing mycobacteria, such as Mycobacterium chelonae and Mycobacterium fortuitum, as well as atypical respiratory pathogens, such as Mycoplasma pneumoniae (20,21,41). In animal pneumonia models, tigecycline has been shown to have effective activity against Legionella pneumophila, Pseudomonas aeruginosa, and Streptococcus pneumoniae pulmonary infections (33).M. pneumoniae is an "atypical" bacterium that lacks a cell wall and plays an important role in acute lower respiratory tract infections in children and adults; approximately 20 to 30% of community-acquired pneumonia in the general population is due to M. pneumoniae (1,3,27,42). In the last few decades, M. pneumoniae respiratory infection has drawn increasing attention for its association with reactive airway disease and asthma (22)(23)(24). Clinical studies have shown that therapy with macrolides or tetracyclines, which are considered the drugs of choice for M. pneumoniae (11), is able to reduce the morbidity of pneumonia, shorten the duration of symptoms, and decrease the recurrence of wheezing (5,7,8,12,25,26). However, even though treatment with macrolide, ketolide, and peptide deformylase inhibitor antimicrobials significantly improves pulmonary inflammation in animal M. pneumoniae pneumonia investigations, M. pneumoniae is not eradicated from the lungs in these in vivo investigations (10,15,31,32). Of note, in these experimental investigations examining the effects of antimicrobials for M. pneumoniae pneumonia, a disassociation is often found between the microbiologic response and the significant improvement observed in other markers of disease severity. While tigecycline demonstrates in vitro activity against M. pneumoniae, tigecycline therapy in vivo for M. pneumoniae pneumonia has not been evaluated. In the present study, we investigate the effect of tigecycline on microbiologic, histologic, and immunologic (pulmonary cytokine and chemokine) parameters in our established murine model of M. pneumoniae pneumonia (9, 10, 14, 15).

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“…In the same surveillance, ciprofloxacin resistance (MIC ≥ 4 μg/mL) was around 5%–7%,31,37 but >85% of these isolates were susceptible to levofloxacin and moxifloxacin. From these data it is deduced that rates of nonsusceptibility to respiratory fluoroquinolones (levofloxacin and moxifloxacin) are not >1% 36.…”

Section: Current Resistances In Respiratory Isolates In the Communitymentioning

confidence: 89%

Drug resistance in community-acquired respiratory tract infections: role for an emerging antibacterial

Aguilar

Giménez²,

Barberán³

2010

IDR

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The nasopharynx is the ecological niche where evolution towards resistance occurs in respiratory tract isolates. Dynamics of different bacterial populations in antibiotic-free multibacterial niches are the baseline that antibiotic treatments can alter by shifting the competitive balance in favor of resistant populations. For this reason, antibiotic resistance is increasingly being considered to be an ecological problem. Traditionally, resistance has implied the need for development of new antibiotics for which basic efficacy and safety data are required prior to licensing. Antibiotic development is mainly focused on demonstrating clinical efficacy and setting susceptibility breakpoints for efficacy prediction. However, additional information on pharmacodynamic data predicting absence of selection of resistance and of resistant subpopulations, and specific surveillance on resistance to core antibiotics (to detect emerging resistances and its link with antibiotic consumption in the community) are valuable data in defining the role of a new antibiotic, not only from the perspective of its therapeutic potential but also from the ecologic perspective (countering resistances to core antibiotics in the community). The documented information on cefditoren gleaned from published studies in recent years is an example of the role for an emerging oral antibacterial facing current antibiotic resistance in community-acquired respiratory tract infections.

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Antibacterial resistance patterns in Streptococcus pneumoniae isolated from elderly patients: PROTEKT years 1–5 (1999–2004)

Cited by 9 publications

References 14 publications

Age-Enhanced Endoplasmic Reticulum Stress Contributes to Increased Atg9A Inhibition of STING-Mediated IFN-β Production during Streptococcus pneumoniae Infection

Age-Enhanced Endoplasmic Reticulum Stress Contributes to Increased Atg9A Inhibition of STING-Mediated IFN-β Production during Streptococcus pneumoniae Infection

Tigecycline Therapy Significantly Reduces the Concentrations of Inflammatory Pulmonary Cytokines and Chemokines in a Murine Model of Mycoplasma pneumoniae Pneumonia

Drug resistance in community-acquired respiratory tract infections: role for an emerging antibacterial

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