scholarly journals Efficacy Profiles of Daptomycin for Treatment of Invasive and Noninvasive Pulmonary Infections with Streptococcus pneumoniae

2009 ◽  
Vol 54 (2) ◽  
pp. 707-717 ◽  
Author(s):  
Stefanie Henken ◽  
Jennifer Bohling ◽  
Jens Martens-Lobenhoffer ◽  
James C. Paton ◽  
A. David Ogunniyi ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Pneumococcal Disease ◽  
Pneumococcal Pneumonia ◽  
Therapeutic Option ◽  
Severe Pneumonia ◽  
Therapeutic Value ◽  
Excellent Activity ◽  
Biophotonic Imaging ◽  
Life Threatening ◽  
Lipopeptide Antibiotic

ABSTRACT Daptomycin is a novel lipopeptide antibiotic with excellent activity against Gram-positive bacterial pathogens, but its therapeutic value for the treatment of invasive pneumococcal disease compared to that for the treatment of pneumococcal pneumonia is incompletely defined. We investigated the efficacy of daptomycin in two models of Streptococcus pneumoniae-induced lung infection, i.e., pneumococcal pneumonia and septic pneumococcal disease. Mice were infected with a bioluminescent, invasive serotype 2 S. pneumoniae strain or a less virulent serotype 19 S. pneumoniae strain and were then given semitherapeutic or therapeutic daptomycin or ceftriaxone. Readouts included survival; bacterial loads; and septic disease progression, as determined by biophotonic imaging. Semitherapeutic daptomycin treatment fully protected the mice against the progression of septic disease induced by serotype 2 S. pneumoniae, while therapeutic treatment of the mice with daptomycin or ceftriaxone led to ∼70% or ∼60% survival, respectively. In contrast, mice infected with serotype 19 S. pneumoniae developed severe pneumonia and lung leakage even in the presence of increased intra-alveolar daptomycin levels, resulting in only 40% survival, whereas the ceftriaxone-treated mice had 100% survival. Together, although daptomycin demonstrates little efficacy in the treatment of pneumococcal pneumonia, daptomycin is highly effective in preventing S. pneumoniae-induced septic death, thus possibly offering a therapeutic option for patients with life-threatening septic pneumococcal disease.

scholarly journals Evaluation of Biophotonic Imaging To Estimate Bacterial Burden in Mice Infected with Highly Virulent Compared to Less Virulent Streptococcus pneumoniae Serotypes

2010 ◽  
Vol 54 (8) ◽  
pp. 3155-3160 ◽  
Author(s):  
Stefanie Henken ◽  
Jennifer Bohling ◽  
A. David Ogunniyi ◽  
James C. Paton ◽  
Vyvyan C. Salisbury ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Disease Progression ◽  
Bacterial Infections ◽  
Pneumococcal Disease ◽  
Bioluminescence Imaging ◽  
Disease Model ◽  
Real Life ◽  
Laboratory Animals ◽  
Mouse Strains ◽  
Biophotonic Imaging

ABSTRACT Bioluminescence imaging is an innovative, noninvasive tool to analyze infectious disease progression under real-life conditions in small laboratory animals. However, the relevance of bioluminescence imaging to monitor invasive compared to noninvasive bacterial infections of the lung has not been examined so far. In the current study, we systematically evaluated the importance of bioluminescence imaging to monitor pneumococcal disease progression by correlating biophotonic signals with lung bacterial loads in two mouse strains (BALB/c, C57BL/6) infected with either self-glowing, bioluminescent serotype 19 Streptococcus pneumoniae causing focal pneumonia or serotype 2 S. pneumoniae causing invasive pneumococcal disease. The best correlations between bioluminescence signals and lung CFU counts were observed in BALB/c mice compared to C57BL/6 mice just on day 3 after infection with invasive serotype 2 S. pneumoniae, while excellent correlations between photon counts and bacterial loads were observed in isolated lungs of BALB/c and C57BL/6 mice, irrespective of the employed pneumococcal serotype. Moreover, good correlations between biophotonic signals and CFU counts were also observed in mice upon infection with serotype 19 S. pneumoniae causing focal pneumonia in mice, again with best correlation values obtained for BALB/c mice at day 3 postinfection. Collectively, we show that the relevance of biophotonic imaging to monitor S. pneumoniae-induced lung infections in mice is largely influenced by the disease model under investigation. The provided data may be important for studies of infectious diseases.

scholarly journals Toll-Like Receptor 4 Agonistic Antibody Promotes Innate Immunity against Severe Pneumonia Induced by Coinfection with Influenza Virus and Streptococcus pneumoniae

2013 ◽  
Vol 20 (7) ◽  
pp. 977-985 ◽  
Author(s):  
Akitaka Tanaka ◽  
Shigeki Nakamura ◽  
Masafumi Seki ◽  
Kenji Fukudome ◽  
Naoki Iwanaga ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Influenza Virus ◽  
Streptococcus Pneumoniae ◽  
Pneumococcal Pneumonia ◽  
Survival Rates ◽  
Severe Pneumonia ◽  
Histopathological Study ◽  
Toll Like Receptor ◽  
Content Type ◽  
Monocyte Chemoattractant Protein 1

ABSTRACTCoinfection with bacteria is a major cause of mortality during influenza epidemics. Recently, Toll-like receptor (TLR) agonists were shown to have immunomodulatory functions. In the present study, we investigated the effectiveness and mechanisms of the new TLR4 agonistic monoclonal antibody UT12 against secondary pneumococcal pneumonia induced by coinfection with influenza virus in a mouse model. Mice were intranasally inoculated withStreptococcus pneumoniae2 days after influenza virus inoculation. UT12 was intraperitoneally administered 2 h before each inoculation. Survival rates were significantly increased and body weight loss was significantly decreased by UT12 administration. Additionally, the production of inflammatory mediators was significantly suppressed by the administration of UT12. In a histopathological study, pneumonia in UT12-treated mice was very mild compared to that in control mice. UT12 increased antimicrobial defense through the acceleration of macrophage recruitment into the lower respiratory tract induced by c-Jun N-terminal kinase (JNK) and nuclear factor kappaB (NF-κB) pathway-dependent monocyte chemoattractant protein 1 (MCP-1) production. Collectively, these findings indicate that UT12 promoted pulmonary innate immunity and may reduce the severity of severe pneumonia induced by coinfection with influenza virus andS. pneumoniae. This immunomodulatory effect of UT12 improves the prognosis of secondary pneumococcal pneumonia and makes UT12 an attractive candidate for treating severe infectious diseases.

scholarly journals 2473 Cardiac injury due to Streptococcus pneumoniae invasion during severe pneumococcal pneumonia in a novel nonhuman primate model

2018 ◽  
Vol 2 (S1) ◽  
pp. 6-6
Author(s):  
Luis F. Reyes ◽  
Cecilia A. Hinojosa ◽  
Nilam J. Soni ◽  
Julio Noda ◽  
Vicki T. Winter ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Pneumococcal Pneumonia ◽  
Troponin I ◽  
Cardiac Injury ◽  
Severe Pneumonia ◽  
Cardiac Events ◽  
Cardiac Damage ◽  
Nonhuman Primate Model ◽  
Primate Model ◽  
Adverse Cardiac Events

OBJECTIVES/SPECIFIC AIMS: The aims of this study are (1) to develop and characterize a novel nonhuman primate model of pneumococcal pneumonia that mimics human disease; and (2) determine whether Streptococcus pneumoniae can: (a) translocate to the heart, (b) cause adverse cardiac events, (c) induce cardiomyocyte death, and (d) lead to scar formation during severe pneumonia in baboons. METHODS/STUDY POPULATION: Six adult baboons (Papio cynocephalus) were surgically tethered to a monitoring system to continuously assess their heart rate, temperature, and electrocardiogram (ECG). A baseline transthoracic echocardiogram, 12-lead ECG, serum troponin-I levels, brain natriuretic peptide, and heart-type fatty acid binding protein (HFABP) levels were obtained before infection and at the end of the experiment to determine cardiovascular damage during pneumococcal pneumonia. Animals were challenged with 108 colony-forming units of S. pneumoniae in the right middle lobe using flexible bronchoscopy. Three baboons were rescued with ampicillin therapy (80 mg/kg/d) after the development of pneumonia. Cardiac damage was confirmed by examination of tissue sections using immunohistochemistry as well as electron and fluorescence microscopy. Western-blots and tissue staining were used to determine the presence of necroptosis (RIP3 and pMLKL) and apoptosis (Caspase-3) in the cardiac tissue. Cytokine and chemokine levels in the heart tissue were determined using Luminex technology. RESULTS/ANTICIPATED RESULTS: Four males (57%) and three (43%) females were challenged. The median age of all baboons was 11 (IQR, 10-19) years old, which corresponds to a middle-aged human. Infected baboons consistently developed severe pneumonia. All animals developed systemic inflammatory response syndrome with tachycardia, tachypnea, fever, and leukocytosis. Infection was characterized by initial leukocytosis followed by severe leukopenia on day 3 postinoculation. Non-specific ischemic alterations by ECG (ST segment and T-wave flattering) and in the premortem echocardiogram were observed. The median (IQR) levels of troponin I and HFABP at the end of the experiment were 3550 ng/mL (1717–5383) and 916.9 ng/mL (520.8–1323), respectively. Severe cardiomyopathy was observed using TEM and H&E stains in animals with severe pneumonia. Necroptosis was detected in cardiomyocytes of infected animals by the presence of pMLKL and RIP3 in cardiac tissues. Signs of cardiac remodeling indicated by disorganized collagen deposition was present in rescued animals but not in the other animals. DISCUSSION/SIGNIFICANCE OF IMPACT: We confirmed that baboons experience cardiac injury during severe pneumococcal pneumonia that is characterized by myocardial invasion, activation of necroptosis, and tissue remodeling in animals rescued by antimicrobial therapy. Cardiac damage by invading pneumococci may explain why adverse cardiac events that occur during and after pneumococcal pneumonia in adult human patients.

scholarly journals Outbreak of invasive pneumococcal disease among shipyard workers, Turku, Finland, May to November 2019

2019 ◽  
Vol 24 (49) ◽  
Author(s):  
Marius Linkevicius ◽  
Veronica Cristea ◽  
Lotta Siira ◽  
Henna Mäkelä ◽  
Maija Toropainen ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Invasive Pneumococcal Disease ◽  
Pneumococcal Disease ◽  
Pneumococcal Pneumonia ◽  
Blood Cultures ◽  
Occupational Hygiene ◽  
Hygiene Measures ◽  
Shipyard Workers

We report an outbreak of invasive pneumococcal disease and pneumococcal pneumonia among shipyard workers, in Turku, Southwest Finland. In total, 31 confirmed and six probable cases were identified between 3 May and 28 November 2019. Streptococcus pneumoniae serotypes 12F, 4 and 8 were isolated from blood cultures of 25 cases. Occupational hygiene measures and vaccination of ca 4,000 workers are underway to control the outbreak at the shipyard.

scholarly journals Continuous renal replacement therapy rescued life-threatening capillary leak syndrome in an extremely-low-birth-weight premature: a case report

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Li-Fen Yang ◽  
Jia-Chang Ding ◽  
Ling-Ping Zhu ◽  
Li-Xia Li ◽  
Meng-Qi Duan ◽  
...  
Keyword(s):  
Birth Weight ◽  
Renal Replacement Therapy ◽  
Low Birth Weight ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Therapeutic Option ◽  
Capillary Leak Syndrome ◽  
Extremely Low Birth Weight ◽  
Capillary Leak ◽  
Life Threatening

Abstract Background Capillary leak syndrome (CLS) is a rare disease characterized by profound vascular leakage and presents as a classic triad of hypotension, hypoalbuminemia and hemoconcentration. Severe CLS is mostly induced by sepsis and generally life-threatening in newborns, especially in premature infants. Continuous renal replacement therapy (CRRT) plays an important role of supportive treatment for severe CLS. Unfortunately, CRRT in preterm infants has rarely been well defined. Case presentation We report the case of a 11-day-old girl with CLS caused by sepsis, who was delivered by spontaneous vaginal delivery (SVD) at gestational age of 25 weeks and 4 days, and a birth weight of 0.89 Kilograms(kg). The infant received powerful management consisting of united antibiotics, mechanical ventilation, intravenous albumin and hydroxyethyl starch infusion, vasoactive agents, small doses of glucocorticoids and other supportive treatments. However, the condition rapidly worsened with systemic edema, hypotension, pulmonary exudation, hypoxemia and anuria in about 40 h. Finally, we made great efforts to perform CRRT for her. Fortunately, the condition improved after 82 h’ CRRT, and the newborn was rescued and gradually recovered. Conclusion CRRT is an effective rescue therapeutic option for severe CLS and can be successfully applied even in extremely-low-birth-weight premature.

scholarly journals Antibodies to Streptococcus pneumoniae Capsular Polysaccharide Enhance Pneumococcal Quorum Sensing

mBio ◽  
2011 ◽  
Vol 2 (5) ◽  
Author(s):  
Masahide Yano ◽  
Shruti Gohil ◽  
J. Robert Coleman ◽  
Catherine Manix ◽  
Liise-anne Pirofski
Keyword(s):  
Monoclonal Antibodies ◽  
Streptococcus Pneumoniae ◽  
Quorum Sensing ◽  
Direct Effect ◽  
Pneumococcal Disease ◽  
Effector Cell ◽  
Capsular Polysaccharide ◽  
Genetic Exchange ◽  
Content Type ◽  
Specific Antibodies

ABSTRACTThe use of pneumococcal capsular polysaccharide (PPS)-based vaccines has resulted in a substantial reduction in invasive pneumococcal disease. However, much remains to be learned about vaccine-mediated immunity, as seven-valent PPS-protein conjugate vaccine use in children has been associated with nonvaccine serotype replacement and 23-valent vaccine use in adults has not prevented pneumococcal pneumonia. In this report, we demonstrate that certain PPS-specific monoclonal antibodies (MAbs) enhance the transformation frequency of two differentStreptococcus pneumoniaeserotypes. This phenomenon was mediated by PPS-specific MAbs that agglutinate but do not promote opsonic effector cell killing of the homologous serotypeinvitro. Compared to the autoinducer, competence-stimulating peptide (CSP) alone, transcriptional profiling of pneumococcal gene expression after incubation with CSP and one such MAb to the PPS of serotype 3 revealed changes in the expression of competence (com)-related and bacteriocin-like peptide (blp) genes involved in pneumococcal quorum sensing. This MAb was also found to induce a nearly 2-fold increase in CSP2-mediated bacterial killing or fratricide. These observations reveal a novel, direct effect of PPS-binding MAbs on pneumococcal biology that has important implications for antibody immunity to pneumococcus in the pneumococcal vaccine era. Taken together, our data suggest heretofore unsuspected mechanisms by which PPS-specific antibodies could affect genetic exchange and bacterial viability in the absence of host cells.IMPORTANCECurrent thought holds that pneumococcal capsular polysaccharide (PPS)-binding antibodies protect against pneumococcus by inducing effector cell opsonic killing of the homologous serotype. While such antibodies are an important part of how pneumococcal vaccines protect against pneumococcal disease, PPS-specific antibodies that do not exhibit this activity but are highly protective against pneumococcus in mice have been identified. This article examines the effect of nonopsonic PPS-specific monoclonal antibodies (MAbs) on the biology ofStreptococcus pneumoniae. The results showed that in the presence of a competence-stimulating peptide (CSP), such MAbs increase the frequency of pneumococcal transformation. Further studies with one such MAb showed that it altered the expression of genes involved in quorum sensing and increased competence-induced killing or fratricide. These findings reveal a novel, previously unsuspected mechanism by which certain PPS-specific antibodies exert a direct effect on pneumococcal biology that has broad implications for bacterial clearance, genetic exchange, and antibody immunity to pneumococcus.

scholarly journals Pneumococcal Pneumonia and Invasive Pneumococcal Disease in Those 65 and Older: Rates of Detection, Risk Factors, Vaccine Effectiveness, Hospitalisation and Mortality

Geriatrics ◽  
2021 ◽  
Vol 6 (1) ◽  
pp. 13
Author(s):  
Roger E. Thomas
Keyword(s):  
Risk Factors ◽  
Nursing Home ◽  
Invasive Pneumococcal Disease ◽  
Disease Transmission ◽  
Pneumococcal Disease ◽  
Pneumococcal Pneumonia ◽  
Clinical Symptoms ◽  
Disease Incidence ◽  
Family Members ◽  
Vaccination Rates

Pneumococcal pneumonia (PP) and invasive pneumococcal disease (IPD) are important causes of morbidity and mortality in seniors worldwide. Incidence rates and serious outcomes worsen with increasing frailty, numbers of risk factors and decreasing immune competence with increasing age. Literature reviews in Medline and Embase were performed for pneumococcal disease incidence, risk factors, vaccination rates and effectiveness in the elderly. The introduction of protein-conjugated pneumoccal vaccines (PCV) for children markedly reduced IPD and PP in seniors, but serotypes not included in vaccines and with previously low levels increased. Pneumococcal polysaccharide (PPV23) vaccination does not change nasal and pharyngeal carriage rates. Pneumococcal and influenza vaccination rates in seniors are below guideline levels, especially in older seniors and nursing home staff. Pneumococcal and influenza carriage and vaccination rates of family members, nursing home health care workers and other contacts are unknown. National vaccination programmes are effective in increasing vaccination rates. Detection of IPD and PP initially depend on clinical symptoms and new chest X ray infiltrates and then varies according to the population and laboratory tests used. To understand how seniors and especially older seniors acquire PP and IPD data are needed on pneumococcal disease and carriage rates in family members, carers and contacts. Nursing homes need reconfiguring into small units with air ventilation externally from all rooms to minimise respiratory disease transmission and dedicated staff for each unit to minimise transmision of infectious diseaases.

When to use the new pneumococcal vaccine

1990 ◽  
Vol 28 (8) ◽  
pp. 31-32
Keyword(s):  
United States ◽  
Pneumococcal Vaccine ◽  
Pneumococcal Disease ◽  
Pneumococcal Pneumonia ◽  
Pneumococcal Infection ◽  
The Elderly ◽  
The United States ◽  
Cell Disease ◽  
Large Groups ◽  
Special Risk

Pneumococcal pneumonia probably affects about one in every thousand adults each year. Like other serious pneumococcal infection, it is more common and severe in the elderly, in those without a functional spleen (including patients with sickle-cell disease,1) and in patients with a variety of chronic diseases. In the United States a 23-valent pneumococcal vaccine was introduced in 1983, replacing a 14-valent vaccine; it is now recommended there for large groups of people.2 This newer 23-valent vaccine (Pneumovax-II - MSD) was licensed in Britain last May. Its use should be considered for those at special risk of pneumococcal disease.3–5

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