EPIDEMIOLOGY OF COMMUNITY EPIDEMIOLOGY OF COMMUNITY ACQUIRED PNEUMONIA IN THE ICUACQUIRED PNEUMONIA IN THE ICU

APRIL 17, 2013 RABEA ALZUBAIDY

Directeur de mémoire : Dr Denis GAROT Service de Réanimation Médicale Polyvalente, CHRU de Tours

MémoireDESC de Réanimation Inter-région Ouest

Université François Rabelais Faculté de médecine de Tours 2012-2013

Community Acquired PneumoniaCommunity Acquired Pneumonia• Epidemiology of CAP and their pathogen

o The etiology remains unknown in approximately one-half of the cases

o Establishing a microbial diagnosis is challenging.

o The role of viruses ??

• The new PCRo Still developing since 1983, recently implemented in clinical practice for bacterial and viral

pathogens

o The multiplex PCR RespiFinder SMART 22®: 21 microorganisms

Jokinen C, Heiskanen L, Juvonen H, et al. Microbial etiology of community-acquired pneumonia in the adult population of 4 municipalities in eastern Finland. Clin Infect Dis 2001; 32(8):1141–1154.

Bartlett, J. M. S.; Stirling, D. (2003). "A Short History of the Polymerase Chain Reaction". PCR Protocols 226. pp. 3–6. doi:10.1385/1-59259-384-4:3. ISBN 1-59259-384-4.

Targets of The RespiFinder®SMART 22

Bacteria• Mycoplasma pneumoniae

• Legionella pneumophila• Chlamydophila pneumoniae

• Bordetella pertussis

DNA Viruses• Adenovirus

• Bocavirus

RNA Viruses• Influenza A

• Influenza A/H1N1• Influenza B

• Coronavirus 229E• Coronavirus HKU1

• Coronavirus NL63• Coronavirus OC43

• Human Metapneumovirus• Parainfluenza Type 1

• Parainfluenza Type 2

• Parainfluenza Type 3• Parainfluenza Type 4

• Respiratory Syncytial Virus A• Respiratory Syncytial Virus B

• Rhinovirus/Enterovirus

Materials and Methods Materials and Methods • Retrospective cohort Study, 37-beds medical ICU (Bretonneau Hospital, University

hospital of Tours, France).• The winter-spring months (from the 1st of November 2011 till the 2nd of May 2012).• All patients with primary diagnosis of CAP:

o Review of the ICU database for CAP diagnosis.o Review of the PCR laboratory database

All discharge summary were reviewed to check for diagnostic criteria of CAP • Data extraction :

o Demographics, outcomeo Microbiological samples :

o Cultures: Blood, endotracheal aspirate or bronchoalveolar lavage.o Urine samples for Streptococcus pneumoniaeand Legionella pneumophilaantigen detection.o Serology for Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophilaand

Coxiella burnetti. o PCR: Nasopharyngeal secretion or bronchoalveolar lavage.

ResultsResultsbaseline characteristics and comorbidities baseline characteristics and comorbidities

• During 6 months, 98 patients with CAP were included.

• A microbial etiology could be identified for 64% (n= 63).Baseline characteristics and risk factors

Characteristics No. of patients (n= 98)Male / Female 61 (62%) / 37 (38%)

Age (years) 63±16.6

Simplified acute physiology score II 37±19

Mechanical ventilation 47 (48%)

Chronic obstructive pulmonary disease 20 (20%)

Other chronic respiratory disease 19 (19%)

Chronic renal failure 10 (10%)

Chronic heart failure 13 (13%)

Hypertension 40 (41%)

Diabetes 22 (22%)

Obesity 10 (10%)

Immunocompromised patient 3 (3%)

Data are presented as count (percentage) and mean±SD

ResultsResultsSpecimensSpecimens

Results Results Overall DistributionsOverall Distributions

Bacteria

n= 40

Viruses

n= 40

Co

-infectio

n

n= 17

Isolated

Bacteria

n= 23

58%

Isolated

Viruses

n= 22

55% Total patients n= 98

Patients with at least one pathogen n= 63

ResultsResultsBacterial InfectionsBacterial Infections

Bacterial pathogens

Pathogen No. of patients (%)

Streptococcus pneumoniae 26 (65%)

Mycoplasma pneumoniae 7 (18%)

Staphylococcus aureus 3 (7.5%)

Legionella pneumophila 1 (2.5%)

Haemophilus influenzae 1 (2.5%)

Neisseria 1 (2.5%)

Acinetobacter baumannii 1 (2.5%)

No bacterial-bacterial co-infection

• 40 patients (63% of the patients with an identified etiology)

ResultsResultsBacterial Infections: Bacterial Infections: Streptococcus PneumoniaeStreptococcus Pneumoniae

• The most frequent pathogen n= 26 patients (41% of the patients with an identified etiology).

• Detection methodso Urine Antigen for 20 patients (78%).o Blood Cultures for 8 patients (31%).o Endotracheal Aspirate for 5 patients (19%).

• 8 cases (31% of streptococcalcases) with viral co-infections (Myxovirus influenzae A and Adenovirus).

ResultsResultsBacterial Infections: Bacterial Infections: Mycoplasma PneumoniaeMycoplasma Pneumoniae

• 7 patients diagnosed by The new PCR (11% of patients with an identified etiology).

• The serologic diagnosis was either negative (n=3) or not contributive in 4 patients

Mycoplasma pneumoniae (PCR versus serology)

No. patients (n=7) PCR 1st serolog 2nd serology

2 Positive Negative Not repeated

2 Positive Not specific Not repeated

3 Positive Negative Negative• Overall serology test was

challengingo 1st serology (n= 44) 45%

o 2nd serology (n= 13) 13%

ResultsResultsViral InfectionsViral Infections

• Virus identifications:

58% Positive Viral

infections (n=40)

ResultsResultsViral InfectionsViral Infections

• 40 patients (63% of the patients with an identified etiology)

• Viral pathogens:

Viruses identifies through PCR

Pathogen Positive patients (n= 40 out of 69 tested patients)

Myxovirus influenzae A 15 (38%)

Bocavirus 11 (28%)

Adenovirus 8 (20%)

Rhinovirus 8 (20%)

Coronavirus 5 (12%)

Human Metapneumovirus 5 (12%)

Parainfluenza Type 3 1 (2%)

Respiratory Syncytial Virus B 1 (2%)

ResultsResultsBacterial viral coBacterial viral co--InfectionsInfections

• n= 17 (27% of the patients with an identified etiology).

Bacterial-viral co-infectionsNo. %

BacteriaStreptococcus pneumoniae 8 47

Mycoplasma pneumoniae 5 29

Staphylococcus aureus 3 18

Neisseria 1 6

VirusesMyxovirus influenzae A 6 35

Adenovirus 6 35

Rhinovirus 4 24

Bocavirus 3 18

Coronavirus 1 6

Parainfluenza virus type 3 1 6

Note: some patients with a bacterial co-infection had more than one virus

ResultsResultsMortalityMortality

• The overall ICU mortality was 15% (n= 15).

DiscussionDiscussion

• The main results of this retrospective study :

o Among two-thirds of patients in whom a pathogen could be identified, Streptococcus pneumoniae, was the most frequently identified pathogen.

o Identification of pathogens with the multiplex PCR tool was frequent. This was particularly important for viruses, observed in more than half of the samples analyzed, and to a lesser extend for Mycoplasma pneumoniae.

• Adults with CAP admitted to hospital were studied prospectively during a 12-month period.

• Microbiological testing methods: same samples collection but different PCR technique (real-time quantitative PCR).

• Results:o n=184

o A microbial etiology could be identified for 67% (n=124).

o The most frequently detected pathogen was S. pneumoniae 56% (n=70).

o Respiratory virus 43% (n=53).

o Co-infections (n=43) 35% (most commonly S. pneumoniae).

Niclas Johansson, Mats Kalin, et al. Etiology of community-acquired pneumonia: increased microbiological yield with new diagnostic methods. Clinical Infectious Diseases 2010; 50:202–9

• A prospective cohort study for CAP and HCAP (in a 28-bed medical ICU); for one year.

• Microbiological testing methods: same samples collection but different PCR technique (real-time quantitative PCR).

• Results for CAP:o n= 198, (CAP n= 64; HCAP n= 134).o A microbial etiology could be identified for 67% (n= 133)o S. pneumoniae: n=23 (17%). o Respiratory virus 54% (n= 72).o Co-infections 14% (n= 18).

Choi SH, Hong SB, Ko GB, et al. Viral infection in patients with severe pneumonia requiring intensive care unit admission. Am J Respir Crit Care Med. 2012;186 (4):325-332

LimitationsLimitations• Uncompleted patients’ information and clinical data.

• Lack of adjustment for confounders of outcomes including severity of disease, comorbidities and complications.

• The interdependence between diagnostic toolso The sample collection was not completed for all patients (only 40% had complete sampling n= 39)o Some samples may not be taken if previous results are known to the physician.

• The exact time of sampling in relation with antibiotics delivery was unknown.

• No firm gold standard diagnostic used for: viruses, Mycoplasma

ConclusionConclusion• The most common pathogen in severe forms of CAP was Streptococcus

pneumoniae… PCR technique soon to come into clinical practice…

• Multiplex PCR was frequently positive in our patients : viruses,Mycoplasma

• Viruses were frequently found and may cause severe forms of pneumonia (either alone or in association with bacteria).

• Co-infections were observed in 1/3 of the patients

• To overcome the limits of this retrospective study we initiated a prospective data collection which started in the winter 2012-2013.

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