Pneumococcal Empyema: Toronto, Ontario 1995-2006Dr. Todd C. LeeKaren Green, Dr. A. McGeer, Dr. D. Low for the Toronto Invasive Bacterial Diseases Network

Presented Nov 15, 2007

What is Empyema? Empyema is an infection of the normally sterile pleural

space Can be diagnosed when pleural fluid is floridly purulent.

A complicated effusion is one that meets the criteria below (CID Dec 1, 2007)

Microbiological diagnosis sputum culturepleural fluid culture blood culture or in some studies molecular techniques such as pleural fluid

PCR or streptococcal antigen.

Development of Empyema

Why Study Empyema?

Within the past several years and co-incident with (but perhaps predating) the introduction of the pneumococcal conjugate vaccine (PCV) in many jurisdictions there has been a dramatic reduction in the overall incidence of invasive pneumococcal disease (IPD). This is particularly noticeable for vaccine strain serotypes and this effect has been seen on multiple continents.

Simultaneous increase in the incidence of pneumococcal empyema (PEMP) emergence of serotype 1 which is consistently associated with a disproportionate

percentage

The majority of studies have focussed on paediatric empyema. Ours would represent one of the largest studies of an adult predominant cohort of patients with empyema recently reported.

Methods

Population based surveillance for invasive pneumococcal disease has been ongoing through TIDBN since 1995.

A database exists for the collection of clinical data from cases with information obtained from the patients themselves, their treating physicians, and retrospective chart review. This data is matched with microbiological data obtained from the isolates.

Empyema in this study was defined as pleural fluid consistent with complicated pleural effusion or empyema with: (1) a positive pleural fluid culture for pneumococcus (2) a clinical diagnosis of empyema with positive blood culture for

pneumococcus.

Non-empyema N=4744

Empyema N=154

P value

Sex (no. % male) 2604 (55%) 91 (59%) NS Age gp <15 yrs 15-64 >64

1018 1740 1929

17 71 64

.004

Institutionally acquired Hospital-acquired Nursing home acquired

204 (4.5%) 309 (6.8%)

9 (4.0%) 6 (6.0%)

NS NS

No underlying chronic illness 2790/4671 (60%) 100/154 (65%) NS Underlying illnesses Cardiac Lung Renal Diabetes mellitus Alcohol abuse HIV infection

(N=4608) 932/3660 (26%) 761/3659 (21%) 241/3660 (6.6%) 663/3372 (20%) 497/3150 (16%) 214/3002 (7.1%)

(N=117) 37/121 (31%) 37/121 (31%) 4/121 (3.3%) 17/114 (14.9%) 26/111 (23.4%) 5/110 (4.5%)

.21 .01 .15 .21 .03 .29

Antibiotic exposure Received any, last 3 mos Failing AB at presentation

1116/3531 (32%) 205/2235 (9.2%)

28/113 (25%) 15/75 (20%)

.12 .004

Outcome ICU Admission Mechanical Ventillation Death

1044/4583 (22.8) 709/4560 (15.5) 889/4658 (19%)

59/153 (38.6) 45/152 (29.6) 31/154(20%)

<0.001 <0.001 NS

Demographics

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

Po

pu

lati

on

Based

Rate

(S

ee L

eg

en

d)

Non Empyema Per 10,000 Empyema Per 100,000

Rates per 100,000 – Age Adjusted

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

Age <15 Age 15-64 Age >=65

Microbiology

Empyema as an Invasive Pneumococcal Disease

Non-empyema Empyema P value Microbiology Serotype 1 Blood Culture Positive Pleural Fluid Culture Pos Both Positive

27/4309 (0.63) 4596/4772 (96.3) NA NA

6/136 (4.4%) 79/154(51.3%) 121/154 (78.5%) 46/121 (38%)

<.001 <.001 NA NA

Vaccine type causing infection Conjugate vaccine Polysaccharide vaccine

2456/4309 (57%) 3751/4309 (87%)

58/136 (43%) 116/136 (85%)

<.001 .54

Antibiotic resistance Penicillin TMP-SMX Erythromycin Ciprofloxacin Levofloxacin Moxifloxacin MDR (>=2 classes)

N=4330 168 (3.9%) 847 (19.6%) 497 (11.5%) 51 (1.2%) 31 (0.8%) 9 (0.2%) 24/130(18%)

N=137 7 (5.1%) 30 (21.9%) 24 (17.5%) 7 (5.3%) 6 (4.6%) 1 (0.8%) 501/4082(12%)

.6 .5 .03 <.001 <.001 .21 .04

Isolate Serotypes

1416%

311%

6B 7%

7F 6%6A

5%9V 5%

14%

12F 4%

19F 4%

23F 4%

OTHER34%

Conjugate Vaccine 4,6B, 9V, 14, 18C,

19F, 23F

Polyvalent Vaccine 1 2 3 4 5 6B 7F 8 9N

9V 10A 11A 12F 14 15B 17F 18C 19F 19A 20 22F 23F 33F

Vaccine Strains by Year

0.0

20.0

40.0

60.0

80.0

100.0

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

Year

Perc

en

tag

e

CONJUGATE VACCINE PERCENTAGE

POLYVALENT VACCINE PERCENTAGE

Clustering of Resistance Resistant Not-Resistant P value Penicillin Erythromycin Resistant TMP/SMX Resistant Levofloxacin Resistant Erythromycin TMP/SMX Resistant Levofloxacin Resistant TMP/SMX Levofloxacin Resistance

11/20(55%) 15/20(75%) 0/20(0%) 14/24 (58%) 1/24(4.2%) 1/30(3.3%)

13/117(11%) 15/117(13%) 6/111(5.4%) 16/116(14%) 5/107(4.7%) 5/101(5.0%)

<.001 <.001 0.59 <.001 1 1

Conjugate Vaccine Serotypes Penicillin Resistance Erythromycin Resistance TMP/SMX Resistance Levofloxacin Resistance

13/20 (65%) 15/24(63%) 19/30(63%) 1/6(17%)

45/116(39%) 43/112(39%) 39/106(37%) 53/124(43%)

0.048 0.04 0.01 0.4

Polyvalent Vaccine Serotypes Penicillin Resistance Erythromycin Resistance TMP/SMX Resistance Levofloxacin Resistance

18/20(90%) 21/24(88%) 23/30(77%) 3/6(50%)

98/116(85%) 95/112(85%) 93/106(88%) 108/124(87%)

0.7 1 0.015 0.04

Resistance to Multiple Agents

Resistance to Multiple Agents MDR NOT MDR P value Male Age <15 15-64 >=65 Nursing Home Nosocomial Any Chronic Illness

12/24 (50%) 4/24 (17%) 12/24 (50%) 8/24 (33%) 3/24 (13%) 0/24 (0%) 9/24 (38%)

65/107 (61%) 13/106 (13%) 47/106 (44%) 46/106 (43%) 3/103 (3%) 8/103 (7.8%) 39/107 (36%)

.36 .6 .08 .35 1

ICU Ventilation Death

10/24 (42%) 5/24 (21%) 2/24 (8.3%)

41/106 (39%) 33/105 (31%) 26/107 (24%)

.8

.45

.1 Positive Blood Culture Conjugate Vaccine Serotypes Polyvalent Vaccine Serotypes

13/24 (54%) 16/24 (67%) 20/24 (83%)

56/107 (52%) 38/106 (36%) 91/106 (86%)

1 0.01 0.75

Resistance over TimePercentage of Resistant Isolates vs Time

0.0

5.0

10.0

15.0

20.0

25.0

30.0

35.0

40.0

45.0

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

Percentage

Yea

r

PCN-R RATE

LEV-R RATE

MDR RATE

Outcomes

Survival Deceased Survived P value Male Age <15 15-64 >=65 Nursing Home Nosocomial No Chronic Illness Lung Disease Cardiac Disease Diabetes Alcohol

21/31 (68%) 1/30 (3.3%) 8/30 (27%) 21/30 (70%) 5/29 (17%) 2/29 (6.9%) 5/31 (16%) 13/26 (50%) 10/31 (32%) 2/26 (7.7%) 10/26 (39%)

70/123 (57%) 16/122 (13%) 63/122 (52%) 43/122 (35%) 1/120 (0.8%) 7/120 (5.8%) 49/123 (39%) 24/95 (25%) 17/123 (14%) 15/88 (17%) 16/85 (19%)

.31 .002 .001 .69 .02 .03 .03 .35 .06

ICU Ventilation

17/30 (57%) 17/30 (57%)

42/123 (34%) 28/122 (23%)

.04

.001 Positive Blood Culture Conjugate Vaccine Serotypes Polyvalent Vaccine Serotypes Penicillin Resistant Erythromycin Resistant TMP/SMX Resisitant Levofloxacin Resistant MDR

21/31 (68%) 8/28 (29%) 21/28 (75%) 4/28 (14%) 1/28 (3.6%) 3/28 (11%) 0/28 (0%) 2/28 (7.1%)

58/123 (47%) 50/108 (46%) 95/108 (88%) 16/109 (15%) 23/109 (21%) 27/109 (25%) 6/103 (5.8%) 22/103 (21%)

.046 0.13 0.13 1 .03 0.13 0.34 .1

ICU Admissions and Deaths By Year

Complications by Year

0.0

10.0

20.0

30.0

40.0

50.0

60.0

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

ICU Admission

Case Fatality Rate

Limitations

Culture negative pneumococcal empyema and patients with sputum cultures only would not be captured by our surveillance.

Eltringham G, Kearns A, Freeman R, Clark J, Spencer D, Eastham K, et al. Culture-negative childhood empyema is usually due to penicillin-sensitive Streptococcus pneumoniae capsular serotype 1. J Clin Microbiol 2003 Jan;41(1):521-2.

~70% of culture negative were pneumoccoccus according to PCR assays. ~60% of these were serotype 1

Examining complicated pleural effusion and empyema rather than empyema exclusively

Limited access (at this point) to patient specific data

Conclusions

In our cohort of patients with pneumococcal empyema: Population based rates were highest in patients older than 65 Cases more likely to be alcohol abusers or have underlying lung

disease Cases were more likely to be failing outpatient therapy There was a high morbidity (40% ICU admission) and mortality

(20% death) associated with pneumococcal empyema Death associated with underlying disease states and more severe

illness Serotype 1 was more common in empyema than in other IPD Isolates found in empyema were more likely to be resistant to

macrolides, ciprofloxacin (not shown) and levofloxacin but not penicillin or moxifloxacin

Acknowledgements

Refik Saskin Karen Green Dr. Allison McGeer Dr. D. Low Toronto Invasive Bacterial Diseases

Network

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