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Opioid Analgesic Use and Risk for Invasive Pneumococcal Diseases: A Nested Case-Control Study.
Wiese AD, Griffin MR, Schaffner W, Stein CM, Greevy RA, Mitchel EF, Grijalva CG
(2018) Ann Intern Med 168: 396-404
MeSH Terms: Adolescent, Adult, Aged, Analgesics, Opioid, Case-Control Studies, Child, Child, Preschool, Female, Humans, Male, Middle Aged, Pneumococcal Infections, Population Surveillance, Retrospective Studies, Risk Factors, Tennessee
Show Abstract · Added July 27, 2018
Background - Although certain opioid analgesics have immunosuppressive properties and increase the risk for infections in animals, the clinical effects of prescription opioid use on infection risk among humans are unknown.
Objective - To test the hypothesis that prescription opioid use is an independent risk factor for invasive pneumococcal disease (IPD).
Design - Nested case-control study.
Setting - Tennessee Medicaid database linked to Medicare and Active Bacterial Core surveillance system databases (1995 to 2014).
Patients - 1233 case patients with IPD aged 5 years and older matched to 24 399 control participants by diagnosis date, age, and county of residence.
Measurements - Opioid use was measured on the basis of pharmacy prescription fills. Invasive pneumococcal disease was defined by the isolation of Streptococcus pneumoniae from a normally sterile site. The odds of current opioid use were compared between the case and control groups, accounting for known IPD risk factors. Secondary analyses categorized opioid use by opioid characteristics, applied an IPD risk score to assure comparability between exposure groups, and analyzed pneumonia and nonpneumonia IPD cases separately.
Results - Persons in the case group had greater odds than control participants of being current opioid users (adjusted odds ratio [aOR], 1.62 [95% CI, 1.36 to 1.92]). Associations were strongest for opioids that were long acting (aOR, 1.87 [CI, 1.24 to 2.82]), of high potency (aOR, 1.72 [CI, 1.32 to 2.25]), or were used at high dosages (50 to 90 morphine milligram equivalents [MME]/d: aOR, 1.71 [CI, 1.22 to 2.39]; ≥90 MME/d: aOR, 1.75 [CI, 1.33 to 2.29]). Results were consistent when the IPD risk score was taken into account and pneumonia and nonpneumonia IPD were analyzed separately.
Limitations - Unmeasured confounding and measurement error, although sensitivity analyses suggested that neither was likely to affect results. Actual opioid use and other nonprescription use (such as illicit opioid use) were not measured.
Conclusion - Opioid use is associated with an increased risk for IPD and represents a novel risk factor for these diseases.
Primary Funding Source - National Institutes of Health.
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16 MeSH Terms
Pneumococcal Community-Acquired Pneumonia Detected by Serotype-Specific Urinary Antigen Detection Assays.
Wunderink RG, Self WH, Anderson EJ, Balk R, Fakhran S, Courtney DM, Qi C, Williams DJ, Zhu Y, Whitney CG, Moore MR, Bramley A, Jain S, Edwards KM, Grijalva CG
(2018) Clin Infect Dis 66: 1504-1510
MeSH Terms: Adult, Aged, Antigens, Bacterial, Community-Acquired Infections, Diagnostic Tests, Routine, Female, Humans, Male, Middle Aged, Pneumococcal Infections, Pneumonia, Bacterial, Serogroup, Urinalysis
Show Abstract · Added July 27, 2018
Background - Streptococcus pneumoniae is considered the leading bacterial cause of pneumonia in adults. Yet, it was not commonly detected by traditional culture-based and conventional urinary testing in a recent multicenter etiology study of adults hospitalized with community-acquired pneumonia (CAP). We used novel serotype-specific urinary antigen detection (SSUAD) assays to determine whether pneumococcal cases were missed by traditional testing.
Methods - We studied adult patients hospitalized with CAP at 5 hospitals in Chicago and Nashville (2010-2012) and enrolled in the Etiology of Pneumonia in the Community (EPIC) study. Traditional diagnostic testing included blood and sputum cultures and conventional urine antigen detection (ie, BinaxNOW). We applied SSUAD assays that target serotypes included in the 13-valent pneumococcal conjugate vaccine (PCV13) to stored residual urine specimens.
Results - Among 1736 patients with SSUAD and ≥1 traditional pneumococcal test performed, we identified 169 (9.7%) cases of pneumococcal CAP. Traditional tests identified 93 (5.4%) and SSUAD identified 76 (4.4%) additional cases. Among 14 PCV13-serotype cases identified by culture, SSUAD correctly identified the same serotype in all of them. Cases identified by SSUAD vs traditional tests were similar in most demographic and clinical characteristics, although disease severity and procalcitonin concentration were highest among those with positive blood cultures. The proportion of pneumonia cases caused by serotypes exclusively covered by PCV13 was not significantly different between the first and second July-June study periods (6.4% vs 4.0%).
Conclusions - Although restricted to the detection of only 13 serotypes, SSUAD testing substantially increased the detection of pneumococcal pneumonia among adults hospitalized with CAP.
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13 MeSH Terms
Efferocytosis-induced prostaglandin E2 production impairs alveolar macrophage effector functions during Streptococcus pneumoniae infection.
Salina AC, Souza TP, Serezani CH, Medeiros AI
(2017) Innate Immun 23: 219-227
MeSH Terms: Animals, Apoptosis, Bacteriolysis, Cyclic AMP, Cyclic AMP-Dependent Protein Kinases, Dinoprostone, Female, Homeostasis, Humans, Hydrogen Peroxide, Jurkat Cells, Macrophages, Alveolar, Phagocytosis, Pneumococcal Infections, Rats, Rats, Wistar, Receptors, Prostaglandin E, EP2 Subtype, Receptors, Prostaglandin E, EP4 Subtype, Signal Transduction, Streptococcus pneumoniae
Show Abstract · Added May 4, 2017
Alveolar macrophages (AMs) are multitasking cells that maintain lung homeostasis by clearing apoptotic cells (efferocytosis) and performing antimicrobial effector functions. Different PRRs have been described to be involved in the binding and capture of non-opsonized Streptococcus pneumoniae, such as TLR-2, mannose receptor (MR) and scavenger receptors (SRs). However, the mechanism by which the ingestion of apoptotic cells negatively influences the clearance of non-opsonized S. pneumoniae remains to be determined. In this study, we evaluated whether the prostaglandin E2 (PGE) produced during efferocytosis by AMs inhibits the ingestion and killing of non-opsonized S. pneumoniae. Resident AMs were pre-treated with an E prostanoid (EP) receptor antagonist, inhibitors of cyclooxygenase and protein kinase A (PKA), incubated with apoptotic Jurkat T cells, and then challenged with S. pneumoniae. Efferocytosis slightly decreased the phagocytosis of S. pneumoniae but greatly inhibited bacterial killing by AMs in a manner dependent on PGE production, activation of the EP2-EP4/cAMP/PKA pathway and inhibition of HO production. Our data suggest that the PGE produced by AMs during efferocytosis inhibits HO production and impairs the efficient clearance non-opsonized S. pneumoniae by EP2-EP4/cAMP/PKA pathway.
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20 MeSH Terms
Nasopharyngeal Pneumococcal Density and Evolution of Acute Respiratory Illnesses in Young Children, Peru, 2009-2011.
Fan RR, Howard LM, Griffin MR, Edwards KM, Zhu Y, Williams JV, Vidal JE, Klugman KP, Gil AI, Lanata CF, Grijalva CG
(2016) Emerg Infect Dis 22: 1996-1999
MeSH Terms: Acute Disease, Bacterial Load, Child, Preschool, Cross-Sectional Studies, Female, Humans, Infant, Infant, Newborn, Male, Nasopharynx, Peru, Pneumococcal Infections, Pneumococcal Vaccines, Population Surveillance, Respiratory Tract Infections, Risk Factors, Streptococcus pneumoniae
Show Abstract · Added July 27, 2018
We examined nasopharyngeal pneumococcal colonization density patterns surrounding acute respiratory illnesses (ARI) in young children in Peru. Pneumococcal densities were dynamic, gradually increasing leading up to an ARI, peaking during the ARI, and decreasing after the ARI. Rhinovirus co-infection was associated with higher pneumococcal densities.
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Persistent Sex Disparities in Invasive Pneumococcal Diseases in the Conjugate Vaccine Era.
de St Maurice A, Schaffner W, Griffin MR, Halasa N, Grijalva CG
(2016) J Infect Dis 214: 792-7
MeSH Terms: Adolescent, Adult, Aged, Child, Child, Preschool, Female, Heptavalent Pneumococcal Conjugate Vaccine, Humans, Incidence, Infant, Infant, Newborn, Male, Middle Aged, Pneumococcal Infections, Pneumococcal Vaccines, Risk Factors, Sex Factors, Tennessee, Young Adult
Show Abstract · Added July 27, 2018
BACKGROUND - Few studies have characterized the role of sex on the incidence of invasive pneumococcal disease (IPD). We examined sex differences in rates of IPD, and trends after the introduction of pneumococcal conjugate vaccines (PCVs).
METHODS - We used active population and laboratory-based IPD surveillance data from the Centers for Disease Control and Prevention Active Bacterial Core surveillance program (1998-2013) in Tennessee. Population-based rates of IPD by sex, race, age group, and PCV era were calculated. Rates were compared using incidence rate ratios.
RESULTS - Throughout the study years, rates of IPD were higher in male than in female subjects, particularly in children <2 years and adults 40-64 years of age, with male subjects having IPD rates 1.5-2 times higher than female subjects. The proportions of comorbid conditions were similar in male and female subjects . Sex rate differences persisted after stratification by race. Although the introductions of 7-valent PCV (PCV7) and 13-valent PCV (PCV13) were associated with declines in IPD rates in both sexes, rates of IPD after PCV13 were still significantly higher in male than in female subjects among children and adults 40-64 and >74 years of age.
CONCLUSIONS - Rates of IPD were generally higher in male than in female subjects. These sex differences were observed in different race groups and persisted after introduction of both PCVs.
© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.
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Bacterial Density, Serotype Distribution and Antibiotic Resistance of Pneumococcal Strains from the Nasopharynx of Peruvian Children Before and After Pneumococcal Conjugate Vaccine 7.
Hanke CR, Grijalva CG, Chochua S, Pletz MW, Hornberg C, Edwards KM, Griffin MR, Verastegui H, Gil AI, Lanata CF, Klugman KP, Vidal JE
(2016) Pediatr Infect Dis J 35: 432-9
MeSH Terms: Anti-Bacterial Agents, Bacterial Load, Child, Preschool, Cross-Sectional Studies, Drug Resistance, Bacterial, Female, Heptavalent Pneumococcal Conjugate Vaccine, Humans, Infant, Male, Microbial Sensitivity Tests, Nasopharynx, Peru, Pneumococcal Infections, Prevalence, Serogroup, Streptococcus pneumoniae
Show Abstract · Added July 27, 2018
BACKGROUND - Pneumococcal conjugate vaccines (PCV) have decreased nasopharyngeal carriage of vaccine types but little data exist from rural areas. We investigated bacterial density, serotype distribution and antibiotic resistance of pneumococcal strains within the nasopharynx of young children in the Peruvian Andes, 2 years after PCV7 was introduced.
METHODS - Pneumococcal strains were isolated from a subset of 125 children from our Peruvian cohort, who entered the study in 2009 and had pneumococcus detected in the nasopharynx in both 2009 and during follow-up in 2011. Strains were Quellung serotyped and tested for susceptibility to antibiotics. Bacterial density was determined by quantitative polymerase chain reaction.
RESULTS - The prevalence of PCV7 strains decreased from 48% in 2009 to 28.8% in 2011, whereas non-PCV7 types increased from 52% to 71.2% (P = 0.002). There was a 3.5-fold increase in carriage of serotype 6C in 2011 (P = 0.026). Vaccination with PCV7 did not affect pneumococcal density in children colonized by a PCV7 type but did increase density in those colonized with a non-PCV7 type. Antibiotic resistance did not change after vaccine introduction; strains were nonsusceptible to tetracycline (97.2%), trimethoprim-sulfamethoxazole (56.4%), penicillin (34%), erythromycin (22.4%), chloramphenicol (18.8%) and clindamycin (12.4%).
CONCLUSIONS - Serotype replacement was observed post-PCV7 vaccination with a concomitant, not previously recognized, increased nasopharyngeal density.
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MeSH Terms
Corynebacterium accolens Releases Antipneumococcal Free Fatty Acids from Human Nostril and Skin Surface Triacylglycerols.
Bomar L, Brugger SD, Yost BH, Davies SS, Lemon KP
(2016) mBio 7: e01725-15
MeSH Terms: Anti-Bacterial Agents, Antibiosis, Carrier State, Child, Child, Preschool, Corynebacterium, Fatty Acids, Nonesterified, Humans, Hydrolysis, Infant, Microbiota, Nasal Cavity, Pneumococcal Infections, Skin, Streptococcus pneumoniae, Triglycerides, Triolein
Show Abstract · Added July 17, 2019
UNLABELLED - Bacterial interspecies interactions play clinically important roles in shaping microbial community composition. We observed that Corynebacterium spp. are overrepresented in children free of Streptococcus pneumoniae (pneumococcus), a common pediatric nasal colonizer and an important infectious agent. Corynebacterium accolens, a benign lipid-requiring species, inhibits pneumococcal growth during in vitro cocultivation on medium supplemented with human skin surface triacylglycerols (TAGs) that are likely present in the nostrils. This inhibition depends on LipS1, a TAG lipase necessary for C. accolens growth on TAGs such as triolein. We determined that C. accolens hydrolysis of triolein releases oleic acid, which inhibits pneumococcus, as do other free fatty acids (FFAs) that might be released by LipS1 from human skin surface TAGs. Our results support a model in which C. accolens hydrolyzes skin surface TAGS in vivo releasing antipneumococcal FFAs. These data indicate that C. accolens may play a beneficial role in sculpting the human microbiome.
IMPORTANCE - Little is known about how harmless Corynebacterium species that colonize the human nose and skin might impact pathogen colonization and proliferation at these sites. We show that Corynebacterium accolens, a common benign nasal bacterium, modifies its local habitat in vitro as it inhibits growth of Streptococcus pneumoniae by releasing antibacterial free fatty acids from host skin surface triacylglycerols. We further identify the primary C. accolens lipase required for this activity. We postulate a model in which higher numbers of C. accolens cells deter/limit S. pneumoniae nostril colonization, which might partly explain why children without S. pneumoniae colonization have higher levels of nasal Corynebacterium. This work narrows the gap between descriptive studies and the needed in-depth understanding of the molecular mechanisms of microbe-microbe interactions that help shape the human microbiome. It also lays the foundation for future in vivo studies to determine whether habitat modification by C. accolens could be promoted to control pathogen colonization.
Copyright © 2016 Bomar et al.
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MeSH Terms
Racial and Regional Differences in Rates of Invasive Pneumococcal Disease.
de St Maurice A, Grijalva CG, Fonnesbeck C, Schaffner W, Halasa NB
(2015) Pediatrics 136: e1186-94
MeSH Terms: Female, Humans, Male, Pneumococcal Infections, Pneumococcal Vaccines, Serogroup, Tennessee, Vaccines, Conjugate
Show Abstract · Added July 27, 2018
BACKGROUND AND OBJECTIVES - Invasive pneumococcal disease (IPD) remains an important cause of illness in US children. We assessed the impact of introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) on pediatric IPD rates, as well as changes in racial and regional differences in IPD, in Tennessee.
METHODS - Data from active laboratory and population-based surveillance of IPD were used to compare IPD rates in the early-PCV7 (2001-2004), late-PCV7 (2005-2009), and post-PCV13 (2011-2012) eras. IPD rates were further stratified according to age, race, and region (east and middle-west TN).
RESULTS - Among children aged <2 years, IPD rates declined by 70% from 67 to 19 per 100 000 person-years in the early-PCV7 era and post-PCV13 era, respectively. Similar decreasing trends in IPD rates were observed in older children aged 2 to 4 years and 5 to 17 years. In the late-PCV7 era, IPD rates in children aged <2 years were higher in black children compared with white children (70 vs 43 per 100 000 person-years); however, these racial differences in IPD rates were no longer significant after PCV13 introduction. Before PCV13, IPD rates in children aged <2 years were also higher in east Tennessee compared with middle-west Tennessee (91 vs 45 per 100 000 person-years), but these differences were no longer significant in the post-PCV13 era.
CONCLUSIONS - PCV13 introduction led to substantial declines in childhood IPD rates and was associated with reduced regional and racial differences in IPD rates in Tennessee.
Copyright © 2015 by the American Academy of Pediatrics.
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MeSH Terms
Restraining the pneumococcus.
Griffin MR, Grijalva CG
(2015) Lancet Infect Dis 15: 491-2
MeSH Terms: Female, Humans, Male, Mass Vaccination, Pneumococcal Infections, Pneumococcal Vaccines, Streptococcus pneumoniae
Added July 27, 2018
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MeSH Terms
Prevention of invasive pneumococcal diseases: beyond cultures.
Grijalva CG, Griffin MR
(2014) Lancet Respir Med 2: 676-7
MeSH Terms: Female, Humans, Male, Pneumococcal Infections, Pneumococcal Vaccines
Added July 27, 2018
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MeSH Terms