Charles Feldman Professor of Pulmonology Charlotte Maxeke Johannesburg Academic Hospital

Charles FeldmanProfessor of Pulmonology

Charlotte Maxeke Johannesburg Academic Hospital University of the Witwatersrand

Abbott, Aspen-GSK,Jansen, MSD, Pfızer, Sanofi

Potential COI to Declare

CAP is one of the leading causes of morbidity and mortality throughout the world – 5.6 million cases diagnosed annually

Little consensus on most appropriate duration of antibiotic therapy and recent recognition that prolonged therapy may be related to development of resistance

A range of recommendations are found encompassing courses of between 5 – 14 days

Introduction to the Talk

1-2 weeks depending on response of patient

Canadian Infectious Diseases Society and Canadian Thoracic

Society

S. pneumoniae and other bacteria: 7-10d Atypical pathogens: may need 10-14 days With new antimicrobials: may shorten to 5-7 days for outpatients

American Thoracic Society

Microbiologically undefined: 7-10 days Legionella species: 14-21 daysAtypical pathogens: 14 daysPneumococci: 7 daysStaphylococci or gram-negative enteric bacilli: 14-21 days

British Thoracic Society

OrganisationRecommended

Duration of TherapyS. pneumoniae: Treat until afebrile for 72hS. aureus, P. aeruginosa, Klebsiella species, anaerobes and atypical pathogens: ≥ 2 weeks

Infectious Diseases Society of America

Short course regimens (< 7 days) theoretically useful in reducing antimicrobial resistance and favouring improved patient compliance

Prolonged treatment especially with low-dose antibiotics was associated with increased carriage of PRSP in nasopharynx (3.5 x and 6 x respectively)

Patient compliance decreases after 5 days of treatment and with resolution of symptoms

Rationale for Short-Course Therapy

Scalera NM et al. Curr Opin Infect Dis 2007; 20: 177-181

Study recruited 2000 children aged 2 – 59 months with non-severe pneumonia (WHO criteria)

Patients randomly assigned to 3 days or 5 days treatment with oral amoxicillin

Primary outcome was treatment failure and analyses were intention to treat

Short Course Therapy - Beta-Lactams

MASCOT Pneumonia Study Group Lancet 2002; 360: 835-841

2000 patients randomised2000 patients randomised

20 excluded• 1 bottle broken• 3 incorrect enrolment• 13 lost to follow-up• 3 treatment changed at home

20 excluded• 1 bottle broken• 3 incorrect enrolment• 13 lost to follow-up• 3 treatment changed at home

27 excluded• 2 bottles broken• 2 incorrect enrolment• 19 lost to follow-up• 4 treatment changed at home

27 excluded• 2 bottles broken• 2 incorrect enrolment• 19 lost to follow-up• 4 treatment changed at home

980 further analysed




127 failed127 failed 116 failed116 failed

853 improved853 improved 857 improved857 improved

45 failed1 died

45 failed1 died

50 failed50 failed

803 resolved803 resolved 811 resolved811 resolved

12 relapsed12 relapsed 13 relapsed13 relapsed

791 cured791 cured 798 cured798 cured

1000 allocated to 5 days amoxicillin

1000 allocated to 5 days amoxicillin

1000 allocated to 3 days amoxicillin1000 allocated to 3 days amoxicillin

Enrolment

1st follow-up (after 3 days)

2nd follow-up (after 5 days)

3rd follow-up (after 14 days)

Treatment failed in 209 (21%) patients in 3-day group and 202 (20%) patients in 5-day group

Overall 12 (1%) children in 3-day group and 13 (1%) children in 5-day group relapsed

Non-adherence was associated with failure of treatment in 5-day group (p<0.0001)

Treatment of Childhood Pneumonia


Overall failure was most likely in children

that did not adhere to treatment (p<0.0001),

less than 12 months (p<0.0001),

whose illness lasted > 3 days (p=0.004),

whose RR was >10 breaths/min above the age specific cut-off (p=0.004),

with vomiting (p=0.009)



Randomised, double-blind, multicentre study in children 2 – 59 months of age with non-severe pneumonia showed oral amoxicillin for three days to be as effective as five days

Cochrane database systematic review confirmed the evidence that short course therapy (3 days) was as effective as longer treatment (5 days) in children < 5 years with non-severe CAP


Agarwal G et al (ISCAP). BMJ 2004; 328: 791Haider BA et al. Cochrane Database Syst Rev 2008; Apr 16; (2): CD005976

Prospective study of hospitalised CAP following the implementation of early switch to oral antibiotics and early hospital discharge showed no difference in safety and patient satisfaction compared to historical controls

Prospective, randomised, parallel group study of non-severe CAP which indicated that abbreviated (2-day) course of i.v. antibiotics with rapid oral switch had similar clinical course and cure rates and lower costs

Treatment of Adult Pneumonia

Lee RW et al. Respirology 2007; 12: 111-116Siegel RE et al. Chest 1996; 110: 965-971

Multicentre, randomised, double-blind study comparing levofloxacin 750mg daily for 5 days versus 500mg daily for 10 days in mild-severe pneumonia

Clinical success rate was 92.4% versus 91.1% and microbiological eradication 93.2% versus 92.4%

Subgroup analysis confirmed benefit in elderly > 65 years

Short Course Therapy - Fluoroquinolones

Dunbar LW et al. Clin Infect Dis 2003; 37: 752-760Shorr AF et al. Clin Ther 2005; 27: 1251-1259

Duration of Antibiotic Therapy in Severe CAP

Patients with community acquired pneumonia:

(1883 patients)

Patients with community acquired pneumonia:

(1883 patients)

CURB 3-5:(574 patients)

CURB 3-5:(574 patients)

Excluded from analysis: 162*• ICU within 7 days (99)• Failed to reach clinical stability in 7 days (118)• Died with 7 days (58)• Complicated pneumonia (11)• Organism requiring prolonged treatment (12)

Excluded from analysis: 162*• ICU within 7 days (99)• Failed to reach clinical stability in 7 days (118)• Died with 7 days (58)• Complicated pneumonia (11)• Organism requiring prolonged treatment (12)

Propensity score derived

Propensity score derived

7 days(164

patients)

7 days(164

patients)

>7 days(164

patients)

>7 days(164

patients)

Out-with mutual range of

propensity score (84)

Out-with mutual range of

propensity score (84)

* Subtotals add up to >162 as some patients

have >1 factor

Choudhury G et al. Clin Microbiol Infect 2011; 17: 1852-1858

Results of the multivariable analysis

CovariateCovariate

Main analysis 7 days vs. >7 days 0.67 (0.21-2.16) p 0.5

Including all patients suitable for matching (N=412) 7 days vs. >7 days

Excluding deaths on treatment 7 days vs. >7 days

0.95 (0.27-3.34) p 0.9

1.20 (0.48-3.02) p 0.7

30-day 30-day mortalitymortality

MV/ISMV/IS Complicated Complicated pneumoniapneumonia

0.92 (0.27-3.16) p 0.9

0.92 (0.27-3.14) p 0.9

1.10 (0.57-2.13) p 0.8

0.63 (0.23-1.71) p 0.4

0.63 (0.23-1.70) p 0.4

0.65 (0.28-1.50) p 0.3

Choudhury G et al. Clin Microbiol Infect 2011; 17: 1852-1858

Potentially relevant trials identified and screened for

retrieval(n=3725)

Potentially relevant trials for which full text was retrieved

(n=38)

Randomised controlled trials included in the meta-

analysis(n=15)

Trials excluded from meta-analysis:

Analysed data from previously includedtrials (n=2)

Did not compare short- vs. extended- course monotherapy (n=18) Minority of subjects with commonly-acquired pneumonia (n=2) Pooled analysis of multiple studies with primary data unavailable (n=1)

Li JZ et al. Am J Med 2007; 120: 783-790

Short Course Therapy – A Meta-analysis

Bohle et al, 1995

Brion et al, 1990

Dunbar et al, 2003

Kinasewits et al, 1991

Kobayashi et al, 1995

Leophante et al, 2002


O’Doherty et al, 1985

Rahav et al, 2004

Rizzato et al, 1995

Schonwald et al, 1994


Sigel et al, 1999

Sopena et al, 2004

Tellier et al, 2004

Overall (95% CI)

0.015412 64.88491

0.92 (0.33-2.54)

1.36 (0.64-2.88)

0.80 (0.62-1.03)

1.06 (0.70-1.63)

0.93 (0.68-1.50)

1.09 (0.72-1.65)

0.90 (0.59-1.35)

1.01 (0.56-1.83)

0.12 (0.02-0.89)

0.33 (0.01-2.84)

0.13 (0.03-0.59)

1.16 (0.64-2.14)

1.11 (0.39-3.19)

0.79 (0.31-2.06)

0.04 (0.65-1.37)

0.89 (0.78-1/02)

Favours short-course Favours extended-course

1.7

2.7

27.8

7.1

7.3

9.9

10.3

5.3

2.0

0.9

3.5

4.0

1.5

2.3

13.6

Risk Ratio(95% CI) % WeightStudy

Li JZ et al. Am J Med 2007; 120: 783-790

Clinical Failure

Bohle et al, 1995

Brion et al, 1990

Dunbar et al, 2003

Kinasewits et al, 1991



Siegal et al, 2999

Tellier et al, 2004

Kobayashi et al, 1995

O’Doherty et al, 1988

Rahav et al, 2004

Rizzato et al, 1995



Sopena et al, 2004

Overall (95% CI)

3.6

11.9

33.8

6.8

12.0

19.6

2.0

10.3

0.0

0.0

0.0

0.0

0.0

0.0

0.0

Risk Ratio(95% CI) % WeightStudy

1.10 (0.07-16.45)

0.83 (0.20-4.38)

0.58 (0.20-1.69)

9.62 (0.06-6.68)

1.22 (0.28-5.37)

0.76 (0.21-2.77)

0.79 (0.12=65.38)

0.72 (0.12-4.29)

(Excluded)

(Excluded)

(Excluded)

(Excluded)

(Excluded)

(Excluded)

(Excluded)

0.81 (0.48-1.43)

0.015294 5.38441

Favours short-course Favours extended-course

Li JZ et al. Am J Med 2007; 120: 783-790

Mortality

Clinical Implications of The Study

Adults with mild-moderate community-acquired pneumonia can be effectively treated with an antibiotic

regimen of 7 days or less

This result is consistent among the 4 antibiotic classes studies (macrolide, fluoroquinolone, beta-lactam, and ketolide)

There is a trend toward decreased adverse events with antibiotic regimens of 7 days or less

Li JZ et al. Am J Med 2007; 120: 783-790

• Comparing different duration courses for different antibacterial

regimens (n=17)• Subgroup analysis of another trial (n=5)• Comparing different dose regimens (n=3)• In children < 2 months of age (n=2)• Not an RCT (n=1)

Six relevant RCTs identified

One more RCT identified by reviewing reference lists

Potentially relevant articles retrieved from the Cochrane

database (n=287)

Articles selected for further evaluation after screening title

and abstract (n=17)

Excluded articles (n=13) after detailed review:

• Comparing different duration courses for different antibacterial

regimens (n=9)• Subgroup analysis of another trial (n=2)• Comparing different dose regimens (n=1)• In children < 2 months of age (n=2)• Not an RCT (n=1)

Four relevant RCTs identified(subset of those identified with the MEDLINE search)

Total of Seven studies selected for inclusion in our meta-analysis

Potentially relevant articles retrieved from MEDLINE

database (n=381)

Articles selected for further evaluation after screening title

and abstract (n=34)

Excluded articles (n=28) after detailed review:

Dimopolous G et al. Drugs 2008; 68: 1841-1854

0.1 0.2 0.5 1 2 5 10

Favours short course Favours long course

Study orSub-Category

Short course(n/N)

Long course(n/N)

OR (fixed)95% CI

Weight(%)

OR (fixed)(95% CI)

Year

2002200420062007

20022004

Studies including adult patientsLeophonte et alTellier et alEl Moussaoui et alFile et alSubtotal (95% CI)Total events: 510 (short course), 506 (long course)Test for heterogeneity: chi2 = 0.46, df = 3 (p = 093), I2 = 0%Test for overall effect: Z = 0.10 (p = 0.746)

81/87143/16

156/60

226/236

544

82/91142/15

950/54

236/247

551

Studies including paediatric patientsMASCOTAgarwal et alSubtotal (95% CI) Total events: 1783 (short course), 1794 (long course)Test for heterogeneity: chi2 = 0.22, df = 1 (p = 0.64), I2 = 0%Test for overall effect: Z = 0.747 (p = 0.46)

Total (95% CI)Total events: 2293 (short course), 2300 (long course)Test for heterogeneity: chi2 = 0.72, df = 5 (p = 0.98), I2 = 0%Test for overall effect: Z = 1.25 (p = 0.21)

2564 2543

811/973983/1026

1999

803/980980/1033

2013

3.486.461.674.38

15.99

62.5021.5184.01

100.00 0.89 (0.74-1.07)

0.67 (0.23-1.98)1.05 (0.52-2.12)0.89 (0.21-3.76)0.85 (0.40-2.28)0.92 (0.58-1.47)

0.91 (0.72-1.15)0.81 (0.54-1.22)0.88 (0.72-1.08)


Clinical Success – End of Therapy

0.1 0.2 0.5 1 2 5 10


Studies including adult patientsSiegel et alLeophonte et alEl Moussaoui et alFile et alSubtotal (95% CI)Total events: 367(short course), 345 (long course)Test for heterogeneity: chi2 = 1.23, df = 3 (p = 0.74), I2 = 0%Test for overall effect: Z = 0.92 (p = 0.36)

20/2267/9249/56

209/227

397

Study orsub-category

Short course(n/N)

Long course(n/N)

1.379.562.385.62

18.84

81.1681.16

100.00

OR (fixed)95% CI

Weight(%)

OR (fixed)(95% CI)

Year

21/2469/9447/52

230/242

412

Studies including paediatric patientsMASCOTSubtotal (95% CI) Total events: 791 (short course), 798 (long course)Test for heterogeneity: not applicableTest for overall effect: Z = 0.747 (p = 0.46)

1392

798/973

973

1370

791/980

980


0.98 (0.80-1.20)

0.70 (0.11-4.64)1.03 (0.54-1.97)1.34 (0.40-4.53)1.65 (0.78-3.51)1.23 (0.79-1.91)

0.92 (0.73-1.15)0.92 (0.73-1.15)

1999200220062007

2002


Clinical Success – Late Follow-up

0.01 0.1 1 10 100


0/227/1192/1950/53

1/254643

1/9730/10932066

2709


Short course(n/N)

Long course(n/N)

3.9455.9015.94

12.1087.88

12.12

12.12

100.00

2.87 (0.11-74.26)

0.53 (0.15-1.86)0.50 (0.05-5.59)Not estimable

0.33 (0.01-8.12)0.60 (0.23-1.85)

0.33 (0.01-8.13)Not estimable

0.33 (0.01-8.13)

0.57 (0.23-1.43)

19992002200420062007

20022004

OR (fixed)95% CI

Weight(%)

OR (fixed)(95% CI)

Year

Studies including adult patientsSigel et alLeophonte et alTellier et alEl Moussaoui et alFile et alSubtotal (95% CI)Total events: 6 (short course), 10 (long course)Test for heterogeneity: chi2 = 1.08, df = 3 (p = 0.78), I2 = 0%Test for overall effect: Z = 1.03 (p = 0.30)

Studies including paediatric patientsMASCOTArgarwal et alSubtotal (95% CI) Total events: 0 (short course), 1 (long course)Test for heterogeneity: not applicableTest for overall effect: Z = 0.68 (p = 0.50)


1/234/1251/1930/56654

2729

0/9800/10952075


Mortality

0.1 0.2 0.5 1 2 5 10


Studies including adult patientsLeophonte et alTellier et alEl Moussaoui et alFile et alSubtotal (95% CI)Total events: 207 (short course), 205 (long course)Test for heterogeneity: chi2 = 2.94, df = 3 (p = 0.40), I2 = 0%Test for overall effect: Z = 0.12 (p = 0.90)

Studies including paediatric patientsMASCOTSubtotal (95% CI) Total events: 43 (short course), 57 (long course)Test for heterogeneity: not applicableTest for overall effect: Z = 1.47 (p = 0.14)

Total (95% CI)Total events: 250 (short course), 262 (long course)Test for heterogeneity: chi2 = 4.30, df = 4 (p = 0.37), I2 = 6.9%Test for overall effect: Z = 0.93 (p = 0.35)

100/125

47/1936/56

54/256630

43/980980

1610

98/11941/19513/63

53/254631

57/973973

1604


Short course(n/N)

Long course(n/N)

12.6719.466.89

26.4865.50

34.5034.50

100.00

0.86 (0.45-1.63)1.21 (0.75-1.95)0.46 (0.16-1.31)1.01 (0.66-1.55)0.98 (0.75-1.29)

0.74 (0.49-1.11)0.74 (0.49-1.11)

0.90 (0.72-1.13)

2002200420062007

2002

OR (fixed)95% CI

Weight(%)

OR (fixed)(95% CI)

Year


Adverse Events

Articles excluded (n=689) because they were:• letters (n=59)• irrelevant (n=239)• review (n=270)• guidelines (n=61)• paediatric population (n=29)• experimental (n=3)• non-RCTs (n=14)• case reports (n=7)• meta-analysis (n=3)• not CAP infection (n=13)

RCTs included in further meta-analysis

(n=6)

Scopus search:1 additional RCT

Potentially relevant articles identified from PubMed

(n=381)

RCTs eligible for further meta-analysis

(n=5)

Athanassa Z et al. Drugs 2008; 68: 2469-2481

0.01 0. 1 1 10 100Favours IV treatment Favours early switch

Siegel et alNorrby et alOmidvari et alCastro-GuardiolaYacub et alOosterheert et al

Total (95% CI)Total events: 333 (early switch), 341 (IV treatment)Test for heterogeneity: chi2 = 6.96, df = 5 (p = 0.22) I2 = 28.2%Test for overall effect: Z = 0.39 (p = 0.69)

18/20105/12755/5839/4823/2593/108

386

16/17112/13936/3754/5522/25

101/121

394

3.6839.454.84

20.103.75

28.28

100.00

0.561.150.510.081.571.23

0.92

[0.05, 6.81][0.62, 2.14][0.05, 5.09][0.01, 0.66][0.24, 10.30][0.59, 2.54]

[0.62, 1.39]

Studyor sub-category

Early switch(n/N)

IV treatment(n/N)

OR (fixed)[95% CI]

Weight(%)

OR (fixed)[95% CI]


Treatment Success

0.01 0. 1 1 10 100Favours IV treatment Favours early switch

Norrby et alOmidvari et alCastro-GuardiolaYacub et alOosterheert et al

Total (95% CI)Total events: 29 (early switch), 34 (IV treatment)Test for heterogeneity: chi2 = 2.04, df = 4 (p = 0.73) I2 = 0%Test for overall effect: Z = 0.84 (p = 0.40)

21/3142/581/480/25

5/132

577

22/3053/370/551/25

8/133

555

61.3410.421.334.33

22.58

100.00

0.920.403.510.320.62

0.81

[0.50, 1.71][0.06, 2.55][0.14, 88.08][0.01, 8.25][0.20, 1.93]

[0.49, 1.33]

Studyor sub-category

Early switch(n/N)

IV treatment(n/N)

OR (fixed)[95% CI]

Weight(%)

OR (fixed)[95% CI]


Mortality

Siegel et al

Omidvari et al

Gastro-Guardiola

Yacub et al

Oosterheert et al

Total (95% CI)

Test for heterogeneity: chi2 = 34.86, df = 4 (p<0.00001), I2 = 88.5%

Test for overall effect: Z = 6.03 (p <0.00001)-10

Study orsub-category N

Early switch mean (SD)

13.70

24.85

18.05

23.89

19.50

100.00

Weight(%)

20

58

48

25

108

259

8.00 (4.00)

7.30 (0.80)

6.00 (4.00)

4.10 (0.92)

9.00 (4.70)

N

17

37

55

25

133

267

IV treatment mean (SD)

11.00 (2.00)

9.70 (0.90)

11.00 (3.00)

8.20 (1.10)

11.30 (4.70)

WMD (random) [95% CI]

WMD (random) [95% CI]

-3.00 (-4.99, -1.01)

-2.40 (-2.76, -2.04)

-5.00 (-6.38, -3.62)

-4.10 (-4.66, -3.54)

-2.30 (-3.49, -1.11)

-3.34 (-4.42, -2.25)

-5 0 5 10

Early switch IV treatment


Hospitalisation

Siegel et al

Norrby et al

Omidvari et al

Gastro-Guardiola

Yacub et al

Total (95% CI)

Test for heterogeneity: chi2 = 3.94, df = 4 (p= 0.041), I2 = 0%

Test for overall effect: Z =1.22 (p = 0.22)0.001


Early switch mean (SD)

7.73

53.01

8.35

6.55

24.35

100.00

Weight(%)

1/20

3/69

2/42

4/48

0/10

189

IV treatment (nN)

0/17

4/85

0/31

0/55

1/8

196

OR 9fixed)) [95% CI]

OR (fixed) [95% CI]

2.69 (0.10, 40.49)

0.92 (0.20, 4.25)

3.89 (0.18, 83.93

11.22 (0.59, 214.08)

0.24 (0.01, 6.69)

1.81 (0.70, 4.72)

0.01 0 10 1000

IV treatment Early switch

0.1 100


Recurrent Infection

24 studies included in systematic review

24 studies included in systematic review

1 study with bacteremic patients excluded

1 study with bacteremic patients excluded

8 studies unclear whether bacteremic patients included

8 studies unclear whether bacteremic patients included

15 studies included bacteremic patients15 studies included bacteremic patients

7 studies with data on bacteremic patient outcomes

7 studies with data on bacteremic patient outcomes

BacteremiaMEDLINE 1445EMBASE 2771Cochrane 1057

BacteremiaMEDLINE 1445EMBASE 2771Cochrane 1057

PeritonitisMEDLINE 664

EMBASE 20231Cochrane 1055

PeritonitisMEDLINE 664

EMBASE 20231Cochrane 1055

CRBSIMEDLINE 302EMBASE 1499Cochrane 1292

CRBSIMEDLINE 302EMBASE 1499Cochrane 1292

PyelonephritisMEDLINE 220EMBASE 825Cochrane 325

PyelonephritisMEDLINE 220EMBASE 825Cochrane 325

PneumoniaMEDLINE 3587EMBASE 15604Cochrane 2000

PneumoniaMEDLINE 3587EMBASE 15604Cochrane 2000

SSTIMEDLINE 673EMBASE 4312Cochrane 827

SSTIMEDLINE 673EMBASE 4312Cochrane 827

21195 records screened












1 study included

1 study included

3 studies included3 studies included




1 study included

1 study included

Havey TC et al. Critical Care 2011, 15:R267

ChowdharyJerneliusSiegelTeller

Total (95% CI)Total events: 29 (early switch), 34 (IV treatment)Test for heterogeneity: chi2 = 3.15, df = 3 (p = 0.37) I2 = 5%Test for overall effect: Z = 1.86 (p = 0.06)

2850

12

45

Study or subgroup

Events

Short Duration

Total

3352

12

52

32438

47

Events

Long Duration

Total

33448

49

Weight(%)

64.59.95.3

20.3

100.0

Risk RatioM-H, Fixed, 95% CI

0.881.000.241.00

0.88

[0.75, 1.02][0.68, 1.46][0.02, 3.19][0.83, 1.21]

[0.77, 1.01]

0. 1 10 100Favours long duration Favours short duration

10. 01


Outcome – Clinical Cure

DunbarRunyonTeller

Total (95% CI)Total events:Heterogeneity: chi2 = 0.51, df = 2 (p = 0.78) I2 = 0%Test for overall effect: Z = 0.69 (p = 0.49)

79

12

28

Study or subgroup Events

Short Duration

Total

79

12

28

6168

30

Events

Long Duration

Total

7178

32

Weight(%)

22.941.635.5

100.0


1.151.041.00

1.05

[0.79, 1.68][0.85, 1.26][0.83, 1.21]

[0.91, 1.21]


10. 01



Outcome – Microbiologıcal Cure

ChaudhryRunyonSiege

Total (95% CI)Total events:Heterogeneity: chi2 = 2.07, df = 2 (p = 0.36) I2 = 3%Test for overall effect: Z = 0.26 (p = 0.79)

591

28

Study or subgroup Events

Short Duration

Total

692

28

7154

30

Events

Long Duration

Total

8174

32

Weight(%)

29.354.116.5

100.0


0.951.100.56

0.97

[0.61, 1.48][0.87, 1.39][0.17, 1.79]

[0.97, 1.23]


10. 01



Outcome – Survival

Bacterial etiology very unlikely

Bacterial etiology very unlikely

Bacterial etiology unlikely

Bacterial etiology unlikely

Bacterial etiology likely

Bacterial etiology likely

Bacterial etiology very likely

Bacterial etiology very likely

Initial antibiotics can be considered in case of:• Respiratory or hemodynamic instability• Need for ICU admission• PCT <0.1 µg/l

• PCT <0.25 µg/l

• Localised injection (abscess, empyema)• Compromised host defence (e.g. Immuno-suppression other than corticosteroids)• Concomitant infection in need of antibiotics

CAP with PSI V or CURB >3COPD with GOLD VICAP with PSI ≥IV or CURB >2COPD with GOLD >III

Control PCT after 6 - 24 hours

If antibiotics are initiated:• Repeated measurement of PCT on days 3, 5, 7• Stop antibiotics using the same cut-offs above • If initial PCT levels are >5-10 µg/l, then stop when

80-90% decrease of peak PCT• If initial PCT remains high, consider treatment failure

(e.g. resistant strain, emypema, ARDS)• Outpatients: duration of antibiotics according to the

last PCT results>0.26 - 0.6 µg/l>0.6 - 1.0 µg/l>1.0 µg/l

Consider the course of PCT

: 3 days: 5 days: 7 days

Procalcitonin (PCT) algorithm for stewardship of antibiotic therapy in patients with LRTIProcalcitonin (PCT) algorithm for stewardship of antibiotic therapy in patients with LRTI

<0.1 µg/l<0.1 µg/l 0.1 -0.25 µg/l0.1 -0.25 µg/l >0.25 – 0.5 µg/l>0.25 – 0.5 µg/l >0.5 µg/l>0.5 µg/l

NO antibiotics!NO antibiotics! No antibioticsNo antibiotics Antibiotics yesAntibiotics yes Antibiotics YES!Antibiotics YES!

Schuetz P et al. Eur J Clin Mico Infect Dis 2010; 29: 269-277

287 outpatients with CAP assessed for eligibility

287 outpatients with CAP assessed for eligibility

115 excluded (not eligible)115 excluded (not eligible)

172 randomised172 randomised

86 randomised to PCT group86 randomised to PCT group 86 randomised to control group86 randomised to control group

4 lost to follow-up 4 withdrew 1 lung cancer

4 lost to follow-up 4 withdrew 1 lung cancer

2 lost to follow-up 4 withdrew 2 pulmonary TB

2 lost to follow-up 4 withdrew 2 pulmonary TB

77 completed interview at 28 days 77 in per-protocol analysis 81 in intention-to-treat analysis




Long W et al. Respirology 2011; 16: 819-824

Patients with CAP should be treated for a minimum of 5 days, should be afebrile for 48 – 72h and should have no more than one CAP-associated sign of clinical instability

Longer duration for certain infections such as S. aureus pneumonia because of risk of endocarditis and deep-seated infections, Pseudomonas aeruginosa infections and atypical pathogens

Common Recommendations

Siegel RE et al. Am J Therapeutics 1999; 6: 217-222

It is reasonable to treat patients with CAP for 5-7 days, if the patient has been afebrile for > 48 hours, has no more than one of CAP-associated signs of clinical instability, and complications of CAP are absent

Concluding Comments

Lim WS et al – BTS Guideline. Thorax 2009Mandell LA et al – IDSA/ATS Guideline. Clin Infect Dis 2007

Hoffken G et al. Pneumologie 2010

Documents

Charles Feldman Professor of Pulmonology Charlotte Maxeke Johannesburg Academic Hospital