Clinical Pathways Library | Children's Hospital of Philadelphia Rab 5 is involved in early endocytosis, Rab 7 is found in the late endosome and Rab 11 is responsible for vacuole recycling (106). Make a referral. Canvin JR, Marvin AP, Sivakumaran M, Paton JC, Boulnois GJ, Andrew PW, Mitchell TJ. 1982. Pneumococcal meningitis is by far the most devastating complication of IPD. 2003. 2004. Tu AH, Fulgham RL, McCrory MA, Briles DE, Szalai AJ. Evaluation of the virulence of a Streptococcus pneumoniae neuraminidase-deficient mutant in nasopharyngeal colonization and development of otitis media in the chinchilla model. 1993. What Is a Pulmonologist: When To See One & What To Expect . On the apical surface, pIgR is cleaved and immunoglobulins are secreted into the lumen. 2016. Hanisch UK, Prinz M, Angstwurm K, Husler KG, Kann O, Kettenmann H, Weber JR. 2001. In vivo this interaction is manifest as decreased nasopharyngeal colonization in mice lacking pIgR and the reduced capacity for S. pneumoniae mutants lacking CbpA to enter the bloodstream (76). 1989. However, these numbers can vary widely based on where the samples are collected from (47). Clinical pathway for pneumonia. The https:// ensures that you are connecting to the TNF: tumor necrosis factor; NO: nitric oxide; PGE2: prostaglandin E2; IC pressure: intracranial pressure. In addition to clinical guidelines in pdf format listed below, more . HHS Vulnerability Disclosure, Help CHOP does not represent or warrant that the clinical pathways are in every respect accurate or complete, or that one or more of them apply to a particular patient or medical condition. 2017. Marks LR, Davidson BA, Knight PR, Hakansson AP. The molecular characterization of the first autolytic lysozyme of Streptococcus pneumoniae reveals evolutionary mobile domains. Dual function of pneumolysin in the early pathogenesis of murine pneumococcal pneumonia. Once established in the alveoli, inflammation is particularly intense resulting in consolidation of the affected lobes. Furthermore, resistance to opsonophagocytic activity of neutrophils is mediated through the action of the exoglycosidases NanA, BgaA and StrH that decrease the amount of C3 being deposited onto the pneumococcal surface (124). These clinical pathways are intended to be a guide for practitioners and may need to be adapted for each specific patient based on the practitioners professional judgment, consideration of any unique circumstances, the needs of each patient and their family, and/or the availability of various resources at the health care institution where the patient is located. Factor H can also be bound by the pneumococcal surface protein Tuf (123). 1999. (This figure contains some artwork produced by Servier Medical Art, (http://smart.servier.com/) under creative commons license 3.0). 2015. Resolution continues for several days as capsule-specific antibodies provide efficient opsonization and inflammatory mediators dissipate (91). Effect of lacto-N-neotetraose, asialoganglioside-GM1 and neuraminidase on adherence of otitis media-associated serotypes of Streptococcus pneumoniae to chinchilla tracheal epithelium. Mannose binding lectin (MBL), a member of the collectin family, binds to carbohydrates such as N-acetyl-glucosamine, a constituent of peptidoglycan (165). The clinical pathways are based upon publicly available medical evidence and/or a consensus of medical practitioners at The Childrens Hospital of Philadelphia (CHOP) and are current at the time of publication. Role of Pneumolysins complement-activating activity during pneumococcal bacteremia in cirrhotic rats, Multiple antibiotic resistance in a bacterium with suppressed autolytic system, Pneumococcal virulence factors: structure and function. PDF CLINICAL PATHWAY: THIS PATHWAY SERVES AS A GUIDE Community Acquired H2O2 is the result of the activity of the enzyme pyruvate oxidase (SpxB) which decarboxylates pyruvate to produce acetyl phosphate, H2O2 and CO2 (38, 97). Risk factors associated with higher rates of carriage include race (particularly Australian Aboriginals and Native Americans) (812), infancy (13, 14), season with higher carriage during winter months (13), and crowded areas such as childcare centers with estimates suggesting 4060% of children who attend childcare are colonized (15). Antibodies specific to bacterial proteins on the cell surface activate the classical pathway (117). Complement activation is not limited to the surface of the bacteria; cell wall fragments released by the bacteria following lysis and during cell wall turnover are also capable of activating complement (170). Interaction of pneumolysin-sufficient and -deficient isogenic variants of Streptococcus pneumoniae with human respiratory mucosa, Inhibition of human polymorphonuclear leukocyte respiratory burst, bactericidal activity, and migration by pneumolysin. Feikin DR, Kagucia EW, Loo JD, Link-Gelles R, Puhan MA, Cherian T, Levine OS, Whitney CG, OBrien KL, Moore MR, Serotype Replacement Study Group. S. pneumoniae undergoes spontaneous phase variation alternating between a transparent and opaque colony phenotype which can be visualized microscopically by oblique transmitted light (32). When infection reaches this stage, a mouse becomes bacteremic. Orihuela CJ, Radin JN, Sublett JE, Gao G, Kaushal D, Tuomanen EI. The polymeric immunoglobulin receptor translocates pneumococci across human nasopharyngeal epithelial cells. Neuraminidases cleave N-acetylneuraminic acid from glycoproteins and glycolipids on the eukaryotic cell surface. 2013. CHOP is not responsible for any errors or omissions in the clinical pathways, or for any outcomes a patient might experience where a clinician consulted one or more such pathways in connection with providing care for that patient. 2000. These factors are reviewed later in the text. A second regulator important in nasopharyngeal colonization is RlrA which regulates the transcription of the pilus-1 structural subunit genes rrg(A-C) (47, 48). The site is secure. Pneumolysin, the thiol-activated toxin of Streptococcus pneumoniae, does not require a thiol group for in vitro activity. 2003. Nonetheless, H2O2 also contributes to mitochondrial damage of neurons resulting in apoptosis (146), and inhibits beating of ciliated ependymal cells lining the ventricular system of the brain and cerebral aqueducts (189, 190). The association between pneumococcal pneumonia and acute cardiac events. Phosphorylcholine (ChoP) decorates the cell wall (Figure 1.) Chop Pneumonia Pathway. The human polymeric immunoglobulin receptor binds to Streptococcus pneumoniae via domains 3 and 4. Most likely all three pathways contribute to bloodstream invasion in an infected animal. Invasive pneumococcal disease in healthy adults: increase of empyema associated with the clonal-type Sweden(1)-ST306. It is believed that CPS inhibits phagocytosis by preventing phagocytes from physically reaching opsonizing serum components, such as complement, CRP, mannose-binding proteins, and antibodies that are deposited on the cell wall and by giving the bacteria a negative charge which repels a close association with leukocytes (32, 114, 115). Cell invasion and pyruvate oxidase derived H. Durand ML, Calderwood SB, Weber DJ, Miller SI, Southwick FS, Caviness VS Jr, Swartz MN. Attachement and invasion of the respiratory tract, p 221237. Davidson M, Parkinson AJ, Bulkow LR, Fitzgerald MA, Peters HV, Parks DJ. Exclusions are noted. Etiology of acute otitis media and serotype distribution of Streptococcus pneumoniae and Haemophilus influenzae in Chilean children <5 years of age. PspK has also been shown to bind the sIgA, however does not appear to be involved in invasion (discussed in further detail below) (53). Hydrogen peroxide (H2O2) is a major product of pneumococcal metabolism and also damages host tissues. Pneumonia - CHOP OPEN Gosink KK, Mann ER, Guglielmo C, Tuomanen EI, Masure HR. The pneumococcal glycolytic enzyme phosphoglycerate kinase (PGK) has been shown to inhibit MAC formation by blocking C9 polymerization (176). 215-590-7491. These mediators combine to produce the symptomatology of pneumococcal infection including changes in blood flow, fluid balance in the tissue, and leukocytosis. Duration of colonization decreases with age and varies from 2 weeks to 4 months (14, 16, 17). The contribution of these virulence products is discussed in greater detail below. Inflammatory components released by the pneumococcus include peptidoglycan, teichoic acid, pneumolysin, hydrogen peroxide, and a number of other secreted proteins. Direct medical costs resulting from infections totaled $3.5 billion (24). Accordingly, these clinical pathways are not intended to constitute medical advice or treatment, or to create a doctor-patient relationship between/among The Childrens Hospital of Philadelphia (CHOP), its physicians and the individual patients in question. Whilst the specific role of biofilm formation in pneumococcal infection is not well understood, it confers an increased resistance to antimicrobial peptides and may promote sharing of genetic information between the bacteria as a result of proximity (56). Inflammation in the cerebrospinal fluid (CSF) exacerbates neuronal damage by releasing matrix metalloproteases such as MMP-9 (142), neurotoxic free radicals such as peroxynitrate (143), and pro-inflammatory cytokines that recruit more leukocytes (141). Bacterial Peptidoglycan Traverses the Placenta to Induce Fetal Neuroproliferation and Aberrant Postnatal Behavior, Expression of C-reactive protein in the human respiratory tract, Regulation of G protein-coupled receptor endocytosis and trafficking by Rab GTPases. Infants, the elderly, and immunocompromised individuals are at an increased risk for developing IPD (2022). Rossjohn J, Feil SC, McKinstry WJ, Tweten RK, Parker MW. Asymptomatic colonization allows the pneumococcus to persist in the population and extensive serotype diversity complicates the development of effective vaccines. Pathways and Resources . The switch from asymptomatic colonization to invasive disease in healthy individuals usually occurs when there is a disruption in the innate immune defenses. Fibrin strands pass through interaveolar connections, also known as the pores of Kohn, from one alveolus to the next and the lymphatics are dilated and filled with cells and fibrin. As many as 80% of children have presented with at least one case of OM (60). Hermans PW, Adrian PV, Albert C, Estevo S, Hoogenboezem T, Luijendijk IH, Kamphausen T, Hammerschmidt S. 2006. The surface of the bacteria mimics this by decorating the cell wall with ChoP. Pneumococcal carriage, p 136147. Molecular analysis of a novel bidirectional pathway. An official website of the United States government. 2002. Mohan S, Hertweck C, Dudda A, Hammerschmidt S, Skerka C, Hallstrm T, Zipfel PF. Sjstrm K, Blomberg C, Fernebro J, Dagerhamn J, Morfeldt E, Barocchi MA, Browall S, Moschioni M, Andersson M, Henriques F, Albiger B, Rappuoli R, Normark S, Henriques-Normark B. Community Acquired Pneumonia Clinical Pathway All Settings Careers, Unable to load your collection due to an error. The pneumococcus can spread from the nasopharynx to a number of different tissues. ICU level patients in the PACU Guide. . Adults Hospitalized With Pneumonia in the United States: Incidence, Epidemiology, and Mortality. Acquisition and invasiveness of different serotypes of Streptococcus pneumoniae in young children. Deletion of htrA alone results in a 100-fold decrease in nasopharyngeal colonization indicating that CiaR/H regulates other factors that contribute to colonization (44). Reduction of inflammation, tissue damage, and mortality in bacterial meningitis in rabbits treated with monoclonal antibodies against adhesion-promoting receptors of leukocytes. 1996. 2001. Wyllie AL, Rmke LW, Arp K, Bosch AA, Bruin JP, Rots NY, Wijmenga-Monsuur AJ, Sanders EA, Trzciski K. 2016. The .gov means its official. This guideline addresses the evaluation and management of well-appearing, term infants, 8 to 60 days of age, with fever 38.0C. Both types of vaccines only introduce the gene for a single protein from the virus that causes COVID-19 - the spike protein. Pneumolysin is a potent pore forming toxin that directly kills host cells and activates complement. Pneumolysin has been demonstrated to slow ciliary beating of epithelial cells (184), disrupt tight junctions (185), and inhibits the capacity of neutrophils and macrophages to kill by inhibiting oxidative burst (186, 187). Park IH, Kim KH, Andrade AL, Briles DE, McDaniel LS, Nahm MH. Sebert ME, Palmer LM, Rosenberg M, Weiser JN. Importantly pneumococcal cell wall products are also inhibitory to cardiac contractility (129), as is pneumolysin which disrupts Ca++ signaling due to pore-formation even if cells are not immediately killed (130). Fedson DS, Musher DM, Eskola J. In pediatric patients, viral infection is the most common cause of CAP. Chop Pneumonia Pathway - .NET Framework Pneumonia & Parapneumonic Effusion Clinical Pathway Multiple studies clearly demonstrate that deletion of the genes that encode autolysin, pneumolysin or the enzyme that produces hydrogen peroxide, greatly attenuates the ability of the bacteria to survive and replicate in the lungs (38, 92, 94, 9698). Topics include: diagnosing viral vs. bacterial pneumonia, use/mis-use of antibiotics, current/future research on pneumonia and more. Dynamic capsule restructuring by the main pneumococcal autolysin LytA in response to the epithelium, Many pulmonary pathogenic bacteria bind specifically to the carbohydrate sequence GalNAc beta 14Gal found in some glycolipids, Effect of neuraminidase on the expression of the 3-fucosyl-N-acetyllactosamine antigen in human tissues, Deacetylation of sialic acid by esterases potentiates pneumococcal neuraminidase activity for mucin utilization, colonization and virulence, Respiratory viruses predisposing to bacterial infections: role of neuraminidase, Role of neuraminidase in lethal synergism between influenza virus and Streptococcus pneumoniae. 1995. 2009. Spellerberg B, Rosenow C, Sha W, Tuomanen EI. Streptococcus pneumoniae phosphoglycerate kinase is a novel complement inhibitor affecting the membrane attack complex formation. Microbiol Spectr. Crook DW, Brueggemann AB, Sleeman KL, Peto TEA. Pettigrew MM, Gent JF, Pyles RB, Miller AL, Nokso-Koivisto J, Chonmaitree T. 2011. Effect of pneumolysin on rat brain ciliary function: comparison of brain slices with cultured ependymal cells. Likewise, pneumolysin released into the milieu also activates complement (171). Nasopharyngeal carriage of Streptococcus pneumoniae by adults and children in community and family settings. In concert, these factors trigger inflammation through multiple inflammatory cascades including the TLR pathway, chemokine/cytokine cascade, the complement cascade, and the coagulation cascade. Classification schemata have helped establish the common organisms responsible for each type of pneumonia and helped to formulate treatment guidelines for efficient management, in both inpatient and outpatient . <2 mo, aspiration pneumonia, immunocompromised, congenital heart disease , BPD, sickle cell , neuromuscular disease , hospital acquired pneumonia , signs of sepsis (follow. These clinical pathways are intended to be a guide for . Lu L, Lamm ME, Li H, Corthesy B, Zhang JR. 2003. Hyperbilirubinemia in the Neonate. Gonzlez-Juarbe N, Bradley KM, Shenoy AT, Gilley RP, Reyes LF, Hinojosa CA, Restrepo MI, Dube PH, Bergman MA, Orihuela CJ. Among CBPs, CbpA is a major pneumococcal adhesin (37) expressed predominantly in the transparent phenotype (35). Torzillo PJ, Hanna JN, Morey F, Gratten M, Dixon J, Erlich J. Our physicians at cham are following standard approaches to providing care for patients. 1989. 1996. Critically, pneumolysin mediated cell death has been shown to be preventable, using drugs that block RIPK1, RIPK3 or MLKL, the signaling pathway involved. Cerebral endothelial cells release TNF-alpha after stimulation with cell walls of Streptococcus pneumoniae and regulate inducible nitric oxide synthase and ICAM-1 expression via autocrine loops, Matrix metalloproteinase-9 in pneumococcal meningitis: activation via an oxidative pathway. Influence of child care on nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae. The binding of MBL to the bacterial cell results in formation of a C3 convertase on the surface of the bacteria and deposition of C3b. Binding of Streptococcus pneumoniae endopeptidase O (PepO) to complement component C1q modulates the complement attack and promotes host cell adherence. Otitis media (OM) is a highly prevalent pediatric disease and the primary cause of physician visits by small children. Likewise CbpA mutants were unable to cross the blood brain barrier despite bacterial titers in the blood of 108 CFU/ml (38). Hgberg L, Geli P, Ringberg H, Melander E, Lipsitch M, Ekdahl K. 2007. PAFr binding is not limited to the pneumococcus, other respiratory pathogens such as Haemophilus spp., Neisseria spp., and Pseudomonas spp., also express ChoP on their surfaces in a phase variable manner (101, 102). NF-B expression then results in production of pro-inflammatory cytokines such as IL-1, IL-6, IL-8, and TNF (159). Intense inflammation is a hallmark of pneumococcal disease and the pneumococcus serves as a prototype for understanding the molecular mechanisms of inflammation in response to gram-positive bacteria (152, 153). Federal government websites often end in .gov or .mil. Antibody-enhanced pneumococcal adherence requires IgA1 protease, Defense mechanisms involving Fc-dependent functions of immunoglobulin A and their subversion by bacterial immunoglobulin A proteases. Although complement is crucial for the opsonization of the bacteria, it also leads to the formation of the membrane attack complex (MAC) formed through the action of C5, C7 and C9 which form a hole in cellular membranes in a fashion similar to pneumolysin. As such, whole viral particles are never produced during vaccine processing. This clinical pathway was developed by a consensus group of JHACH physicians, pharmacists, PAs and APRN(s) to standardize the management of pneumonia in otherwise healthy infants and children (age greater than 90 days). Clinical pathway for pneumonia Best Pract Benchmarking Healthc. Butler JC. In addition to the pathology derived from inflammation, the pneumococcus can directly damage eukaryotic cells. Impact of pneumococcal conjugate vaccines on nasopharyngeal carriage and invasive disease among unvaccinated people: review of evidence on indirect effects. Worldwide, it is estimated that S. pneumoniae is responsible for 15 cases of IPD per 100,000 persons per year (23), and over a million deaths annually. Clinical pathway for pneumonia - PubMed Yao H, Zhang H, Lan K, Wang H, Su Y, Li D, Song Z, Cui F, Yin Y, Zhang X. Bacterial meningitis in the United States, 19982007, Treatment of Drug-resistant Pneumococcal Meningitis. In defense against the widespread expression of ChoP on respiratory pathogens, the host deploys C-reactive protein (CRP), an acute phase reactant that activates complement and opsonizes the bacteria (105). The key surface component recognized by the innate immune system is the cell wall (Figure 4.). Barocchi MA, Ries J, Zogaj X, Hemsley C, Albiger B, Kanth A, Dahlberg S, Fernebro J, Moschioni M, Masignani V, Hultenby K, Taddei AR, Beiter K, Wartha F, von Euler A, Covacci A, Holden DW, Normark S, Rappuoli R, Henriques-Normark B. Zhang JR, Mostov KE, Lamm ME, Nanno M, Shimida S, Ohwaki M, Tuomanen E. 2000. Mucosal epithelial cells transport IgA and IgM in a vesicle moving from the basolateral to the apical surface by binding to pIgR. Furthermore, it has been shown that LytA is important for the release of capsule in response to antimicrobial peptides found on the epithelial surface (78). Pneumonia may be lobar (affects one or more sectionslobesof the lungs) or bronchial (affects patches throughout both lungs, also called "bronchopneumonia"). Kastenbauer S, Koedel U, Pfister HW. Weber JR, Angstwurm K, Brger W, Einhupl KM, Dirnagl U. 2013. Similarly, CPS and cell walls bind to hydrolyzed C3 and activate the alternative complement pathway (156, 163, 164). In mice and non-human primates, cardiac damage ensues in the form of microscopic lesions in the myocardium (126, 127) caused by the release of pneumolysin and H2O2 with added pathology resulting from the influx of immune cells (126, 128). Role of peroxynitrite as a mediator of pathophysiological alterations in experimental pneumococcal meningitis. 2013. Both family 1 and family 2 PspA proteins can inhibit complement deposition and confer virulence to a capsular serotype 3 strain of Streptococcus pneumoniae. Community-Acquired Pneumonia: Respiratory: High Flow Nasal Cannula Therapy: Initiation and Escalation . Our Clinical Pathways Program within the Center for Healthcare Quality & Analytics aims to incorporate evidence, best practice, and local expert consensus into easily accessible, shared mental models for use by clinical teams at the point of care to facilitate the delivery of high-quality medical care. Pneumococcal cell wall, pneumolysin and hydrogen peroxide are the virulence determinants that mediate the greatest inflammation and cytotoxicity observed in the lungs (9294). Binding of C3b proceeds by a transesterification reaction at the thiolester site. Chelating extracellular calcium inhibits the release of AIF and protects cells from pneumolysin-induced apoptosis in vitro. Comis SD, Osborne MP, Stephen J, Tarlow MJ, Hayward TL, Mitchell TJ, Andrew PW, Boulnois GJ. Biofilm formation enhances fomite survival of Streptococcus pneumoniae and Streptococcus pyogenes. The teichoic and lipoteichoic acids are indicated as dark blue lines bearing choline (circles). Molecular surveillance on Streptococcus pneumoniae carriage in non-elderly adults; little evidence for pneumococcal circulation independent from the reservoir in children. However, PepO expression in the lungs has been suggested to trigger release of the chemoattractant IL-8 and IP-10 which leads to neutrophil recruitment and contributes to the host response pathology (169). Studies have also colocalized PAFr with adherent bacteria on the surface of human cells (100). Polysaccharide Capsule Composition of Pneumococcal Serotype 19A Subtypes Is Unaltered among Subtypes and Independent of the Nutritional Environment. Structure of a cholesterol-binding, thiol-activated cytolysin and a model of its membrane form. Brown AO, Mann B, Gao G, Hankins JS, Humann J, Giardina J, Faverio P, Restrepo MI, Halade GV, Mortensen EM, Lindsey ML, Hanes M, Happel KI, Nelson S, Bagby GJ, Lorent JA, Cardinal P, Granados R, Esteban A, LeSaux CJ, Tuomanen EI, Orihuela CJ. Help is currently not implemented . The Clinical Pathways Program aims to improve the quality of care provided to patients at Yale New Haven Children's Hospital. Pneumococcal vaccine In Plotkin SA, Ordenstein WA (ed). The introduction of pneumococcal conjugate vaccines has reduced carriage rates for serotypes covered by the vaccine while non-vaccine serotypes have emerged to occupy this empty niche (18). PspK of Streptococcus pneumoniae increases adherence to epithelial cells and enhances nasopharyngeal colonization. How contagious are common respiratory tract infections? 1997. 267-425-3333. Anti ICAM-1 (CD 54) monoclonal antibody reduces inflammatory changes in experimental bacterial meningitis. PspA has been demonstrated to inhibit complement activation mediated via the classical pathway on the bacteria surface (117, 118). Once the pneumococcus is in the middle ear, inflammation is triggered by pneumolysin and cell wall components (70). 2023 by Children's Hospital of Philadelphia, all rights reserved. PspA allows the bacteria to reduce C3 deposition, whereas Factor H, a negative regulator of the alternative pathway, leads to interference of the formation of the C3 convertase. Uptake of the pneumococcus into a vacuole involves clathrin followed by recruitment of -arrestin scaffold, Rab5, then Rab7 and Rab11. At Seattle Children's, a clinical standard work (CSW) pathway is a documented approach to the management and treatment of a particular population or clinical condition. Chao Y, Marks LR, Pettigrew MM, Hakansson AP. Gram positive bacteria, such as Streptococcus, are also in general more resistance to MAC killing than their Gram negative counterparts since they lack an outer membrane leaving MAC to form on the thick peptidoglycan wall. In vitro, pneumococci adhere more efficiently to tissue culture cells treated with neuraminidase (77).
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