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Microbial Etiology of Pneumonia: Epidemiology, Diagnosis and Resistance Patterns

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Microbial Etiology of Pneumonia: Epidemiology, Diagnosis and Resistance Patterns International Journal of Molecular Sciences Review Microbial Etiology of Pneumonia: Epidemiology, Diagnosis and Resistance Patterns Catia Cilloniz 1, Ignacio Martin-Loeches 2, Carolina Garcia-Vidal 3, Alicia San Jose 1 and Antoni Torres 1,* 1 Department of Pneumology, Institut Clinic del Tórax, Hospital Clinic of Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Ciber de Enfermedades Respiratorias (CIBERES), 08036 Barcelona, Spain; [email protected] (C.C.); [email protected] (A.S.J.) 2 Department of Clinical Medicine, Trinity Centre for Health Sciences, Multidisciplinary Intensive Care Research Organization (MICRO), Welcome Trust-HRB Clinical Research, St James’s Hospital, St James’s University Hospital, Dublin, Ireland; [email protected] 3 Department of Infectious Diseases, Hospital Clinic of Barcelona, 08036 Barcelona, Spain; [email protected] * Correspondence: [email protected]; Tel.: +34-93-227-5779, Fax: +34-93-227-9813 Academic Editor: Susanna Esposito Received: 18 October 2016; Accepted: 13 December 2016; Published: 16 December 2016 Abstract: Globally, pneumonia is a serious public health concern and a major cause of mortality and morbidity. Despite advances in antimicrobial therapies, microbiological diagnostic tests and prevention measures, pneumonia remains the main cause of death from infectious disease in the world. An important reason for the increased global mortality is the impact of pneumonia on chronic diseases, along with the increasing age of the population and the virulence factors of the causative microorganism. The increasing number of multidrug-resistant bacteria, difficult-to-treat microorganisms, and the emergence of new pathogens are a major problem for clinicians when deciding antimicrobial therapy. A key factor for managing and effectively guiding appropriate antimicrobial therapy is an understanding of the role of the different causative microorganisms in the etiology of pneumonia, since it has been shown that the adequacy of initial antimicrobial therapy is a key factor for prognosis in pneumonia. Furthermore, broad-spectrum antibiotic therapies are sometimes given until microbiological results are available and de-escalation cannot be performed quickly. This review provides an overview of microbial etiology, resistance patterns, epidemiology and microbial diagnosis of pneumonia. Keywords: microbial etiology; pneumonia; diagnosis 1. Introduction In 2014, the eighth cause of mortality in the United States reported by the National Center for Health Statistics was influenza and pneumonia together [1]. In children, pneumonia is the single largest infectious cause of death worldwide. In 2015, pneumonia killed 920,136 children under the age of 5, accounting for 15% of all deaths of children under five years old [2]. Pneumonia infection is the result of a complex process where the lower respiratory tract suffers the invasion of an infective microorganism. Pneumonia can be acquired in the community or acquired in the hospital environment, and can be transmitted by the aspiration of a pathogenic microorganism or by inhalation of a pathogenic microorganism. It is important to know the role of the pathogenic microorganism in the etiology of a pneumonia infection in order to provide adequate clinical and therapeutic management of the patient. Globally, Streptococcus pneumoniae (pneumococcus) is the most common pathogen causing community-acquired pneumonia. Pneumococcus was considered one of the 9 bacteria of international Int. J. Mol. Sci. 2016, 17, 2120; doi:10.3390/ijms17122120 www.mdpi.com/journal/ijms Int. J. Mol. Sci. 2016, 17, 2120 2 of 18 international concern in the recent worldwide report of global antibiotic resistance published by the Int.World J. Mol. Health Sci. 2016 Organization, 17, 2120 (WHO) in 2014 [3]. On the other hand, a wide range of pathogens2 of 18 acquired either from the patient or from the hospital environment can cause nosocomial concernpneumonia. in the However, recent worldwide Gram-negative report ofbacteria global are antibiotic more resistancefrequent than published Gram-positive by the World bacteria Health in Organizationthese cases. (WHO) in 2014 [3]. On the other hand, a wide range of pathogens acquired either from the patientThis or fromreview the summarizes hospital environment important canfeatures cause and nosocomial management pneumonia. issues However,regarding Gram-negative the microbial bacteriaetiology areof morepneumonia, frequent focusing than Gram-positive on epidemiology, bacteria pathogenesis, in these cases. diagnostic testing and resistance patterns.This review summarizes important features and management issues regarding the microbial etiology of pneumonia, focusing on epidemiology, pathogenesis, diagnostic testing and 2. Microbial Etiology of Community-Acquired Pneumonia (CAP) resistance patterns. 2.2.1. Microbial Epidemiology Etiology of Community-Acquired Pneumonia (CAP) In 2013, the Global Burden of Disease Study based on data from 188 countries around the 2.1. Epidemiology world, reported that lower respiratory tract infection was the second most common cause of death [4]. InIn Europe, 2013, the mortality Global Burden rates for of DiseaseCAP vary Study widely based from on datacountry from to 188 country, countries ranging around from the <1% world, to reported48% [5]. that lower respiratory tract infection was the second most common cause of death [4]. In Europe,The study mortality by Jain rates et al. for [6] CAP about vary etiology widely fromof CAP country showed to country, an increased ranging incidence from <1% of CAP to 48% with [5]. increasingThe study patient by Jainage; etthe al. annual [6] about incidence etiology of of pneumonia CAP showed in anthe increased USA was incidence 24.8 cases of per CAP 10,000 with increasingadults, with patient the highest age; the rates annual among incidence adults of pneumoniaaged between in the65 USAand 79 was years 24.8 casesof age per (63.0 10,000 cases adults, per with10,000 the adults) highest and rates those among aged adults 80 years aged or betweenolder (164.3 65 and cases 79 per years 10,000 of age adults). (63.0 cases per 10,000 adults) and thoseThe economic aged 80 years cost orrelated older (164.3to CAP cases remains per 10,000 high. adults). A recently published Dutch study that includedThe economic195,372 CAP cost relatedcases reported to CAP remains that the high. median A recently costs publishedof CAP cases Dutch were study conditional that included on 195,372patient CAPage and cases class reported of treatment that the care, median varying costs offrom CAP €344 cases per were case conditional for patients on 0 patient to 9 years age andold classtreated of as treatment outpatients, care, to varying €10,284 from per €episode344 per for case 50 for–64 patients year olds 0 to admitted 9 years oldto the treated intensive as outpatients, care unit to(ICU)€10,284 [7]. per episode for 50–64 year olds admitted to the intensive care unit (ICU) [7]. 2.2. Causative Microorganism Several studiesstudies onon the the microbial microbial etiology etiology of CAPof CAP have have been been published published in recent in recent years years [6,8]. Some[6,8]. ofSome them of showedthem showed that microbial that microbial causes causes of CAP of differ CAP accordingdiffer according to the severityto the severity of disease of disease at clinical at presentationclinical presentation [9]. A Spanish [9]. A studySpanish regarding study regarding the relationship the relationship of microbial of etiology microbial of CAPetiology and severity,of CAP concludedand severity, that concluded pneumococcus that pneumococcus is the most frequent is the mo pathogenst frequent in allpathogen sites of in care. all Thesites secondof care. most The frequentsecond most group frequent of pathogens group was of intracellularpathogens microorganisms,was intracellular followed microorganisms, by polymicrobial followed cases by (Figurepolymicrobial1). cases (Figure 1). (A): abbreviations: GNEB = Gram-negative enteric bacilli. Figure 1. Cont. Int. J. Mol. Sci. 2016, 17, 2120 3 of 18 Int. J. Mol. Sci. 2016, 17, 2120 3 of 18 (B): abbreviations: GNEB = Gram-negative enteric bacilli. (C): abbreviations: ICU = intensive care unit; GNEB = Gram-negative enteric bacilli. Figure 1. The most commonly identified pathogens among adults with Community-acquired Figure 1. The most commonly identified pathogens among adults with Community-acquired pneumonia in Spain [8]. (A) Outpatients; (B) Patients Admitted to Ward; (C) Patients Admitted to pneumonia in Spain [8]. (A) Outpatients; (B) Patients Admitted to Ward; (C) Patients Admitted Intensive Care Unit. to Intensive Care Unit. Although microbiological diagnosis of CAP is fundamental to ensure appropriate antibiotic therapy,Although which microbiologicalis associated with diagnosis decreasing of CAP mortality is fundamental [10], microbial to ensure diagnosis appropriate of pneumonia antibiotic is achievedtherapy, whichin less isthan associated 50% of cases with and decreasing antimicrobial mortality therapy [10], should microbial be empirically diagnosis of administered pneumonia in is orderachieved to avoid in less the than delay 50% in of establishing cases and antimicrobialappropriate therapy, therapy associated should be with empirically significant administered mortality [11,12].in order to avoid the delay in establishing appropriate therapy, associated with significant mortalityGlobally, [11,12 Streptococcus]. pneumoniae
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