Respiratory infections in ICU setting: diagnostic and therapeutic challenges Microbiology Residency Program. KFHU, Al Khobar

1. RESPIRATORY
INFECTIONS IN ICU
SETTING: DIAGNOSTIC
AND THERAPEUTIC
CHALLENGES
Abdullatif Sami Al Rashed
Microbiology Resident
Demonstrator, Department of Microbiology, College of
Medicine, Imam Abdulrahman Bin Faisal University
Dammam, Saudi Arabia
16/09/2020

2. Outlines
Introduction
Case
senarios

3. Introduction
• Patients in ICUs have more chronic comorbid illnesses and more
severe acute physiologic changes compared with patients in the
general hospital population and thus are relatively
immunosuppressed.
• They are also subjected to increased selective pressure and
increased colonization pressure.
• More than 20 % of all nosocomial infections are acquired in ICUs.
• Respiratory infections are by far the most challenging nosocomial
complications in intensive care units (ICUs)
Martin-Loeches I, Povoa P, Rodríguez A, et al. Incidence and prognosis of ventilator-associated tracheobronchitis (TAVeM): a multicentre,
prospective, observational study. Lancet Respir Med 2015; 3: 859–868

4. Lord Akryl, Jmarchn. 2010

5. Respiratory Infections in ICU
Community
acquired
infections
•Community-acquired pneumonia (CAP):
Hospital acquired
and health care
associated
infections
• Hospital-acquired pneumonia (HAP):
• ventilator-associated pneumonia (VAP):
Refers to an acute infection of the pulmonary parenchyma acquired
outside of the hospital or a long-term care facility.
Refers to pneumonia acquired ≥48 hours after hospital admission.
Refers to pneumonia acquired ≥48 hours after endotracheal intubation.

6. Spectrum of different isolates from lower respiratory tract
specimen in ICU patients with LRTI
Bajpai T, Shrivastava G, Bhatambare GS, Deshmukh AB, Chitnis V. Microbiological profile
of lower respiratory tract infections in neurological intensive care unit of a tertiary care
center from Central India. Journal of basic and clinical pharmacy. 2013 Jun;4(3):51.

7. CASE 1:
Chronic Productive cough & weight loss in middle aged women

8. Case
presentation
Thamer H. Alenazi, Bashayer S. Alanazi, Abdulrahman Alsaedy, Abdulmoneim Khair, Rifat Solomon,
Sameera M. Al Johani, Mycobacterium riyadhense as the opportunistic infection that lead to HIV diagnosis: A
report of 2 cases and literature review, Journal of Infection and Public Health, Volume 12, Issue 2, 2019,
Pages 285-288, ISSN 1876-0341.
A 44-year-old female, with a known case
of hypothyroidism presented to King
Abdulaziz Medical City-Riyadh, on July,
2013 with one month history of
productive cough with yellowish sputum
& shortness of breath (SOB), and fever.
She reported a history of unintentional
weight loss, about 8 kg in the last month,
otherwise her history was unremarkable.

9. Case presentation
• On physical examination, she was febrile with a temperature of
38.9 °C and a respiratory rate of 24 breaths per minute.
• Respiratory exam showed decreased breath sounds and
bilateral coarse crepitations at both bases.
• Other exam was unremarkable.
Thamer H. Alenazi, Bashayer S. Alanazi, Abdulrahman Alsaedy, Abdulmoneim Khair, Rifat Solomon, Sameera M. Al Johani, Mycobacterium riyadhense
as the opportunistic infection that lead to HIV diagnosis: A report of 2 cases and literature review, Journal of Infection and Public Health, Volume 12,
Issue 2, 2019, Pages 285-288, ISSN 1876-0341,

10. DDX &
MICROBIOLOGICAL
INVESTIGATIONS
❓❓❓❓

11. Cough is divided into three categories: acute, defined as lasting less than three weeks; subacute, lasting
three to eight weeks; and chronic, lasting more than eight weeks Irwin RS, et al. 2006
Differenitial Diagnosis
Infectious Non-infectous
CAP Lung cancer
TB Sarcoidosis
Lung abscess Lymphoma
Nocardiosis Septic emboli
PCP Constrictive Pericarditis
NTM Bronchiectasis
Fungal infections (Invasive aspergillosis, cryptococcous,
histoplasmosis, Blastomycosis.. etc)
Menzies D, Joshi R, Pai M. Risk of tuberculosis infection and disease associated with work in health care settings. Int J Tuberc
Lung Dis. 2007 Jun. 11(6):593-605.

12. CAP HAP
VAP
Oxford Handbook of Infectious Diseases. 2nd ed
Common causes

13. Aerobic Anaerobic others
s.aureus Peptostreptococcus MTB
S.anginuses Fusobacterium
nucleatum
Nocardia
E.coli Prevotella Fungal (Aspergillus
and Cryptococcus
spp)
K.pneumonia
P.aeruginosa
S.pneumoniae
Lung abscess causes :
Menzies D, Joshi R, Pai M. Risk of tuberculosis infection and disease associated with work in health care settings. Int J Tuberc
Lung Dis. 2007 Jun. 11(6):593-605.

14. Case cont.
•What Tests should be ordered ?

15. Diagnostic Approach
Clinical
findings
General lab
tests
Radiology
Microbiological
tests

16. When shall we order a Blood or
sputum culture for a case of CAP ?
IDSA : blood/sputum cultures are optional for patients without these conditions.

18. Case presentation
• Her complete blood counts showed WBC of
9 × 109/L. Erythrocytes sedimentation rate (ESR) was 30 mm/h.
• Chest X-ray revealed right perihilar infiltration extending to the
right upper lobe. No plural effusion.
• Sputum culture for bacterial & 3 sputum samples for AFB stain
and culture has been taken.
• Patient was admitted as a case of community acquired
pneumonia and started on ceftriaxone and azithromycin.
Thamer H. Alenazi, Bashayer S. Alanazi, Abdulrahman Alsaedy, Abdulmoneim Khair, Rifat Solomon, Sameera M. Al Johani, Mycobacterium riyadhense
as the opportunistic infection that lead to HIV diagnosis: A report of 2 cases and literature review, Journal of Infection and Public Health, Volume 12,
Issue 2, 2019, Pages 285-288, ISSN 1876-0341,

19. Case presentation
• Bacterial Sputum culture shows no growth
• First sputum sample for AFB stain & MTB PCR were
negative. (culture is in progress)
Thamer H. Alenazi, Bashayer S. Alanazi, Abdulrahman Alsaedy, Abdulmoneim Khair, Rifat Solomon, Sameera M. Al Johani, Mycobacterium riyadhense
as the opportunistic infection that lead to HIV diagnosis: A report of 2 cases and literature review, Journal of Infection and Public Health, Volume 12,
Issue 2, 2019, Pages 285-288, ISSN 1876-0341,

20. Case presentation
• In the 4th day she became hemodynamic unstable and hypoxic,
so she was shifted to the Intensive Care Unit (ICU).
• Blood and transtracheal aspiration cultures have been taken.
Thamer H. Alenazi, Bashayer S. Alanazi, Abdulrahman Alsaedy, Abdulmoneim Khair, Rifat Solomon, Sameera M. Al Johani, Mycobacterium riyadhense
as the opportunistic infection that lead to HIV diagnosis: A report of 2 cases and literature review, Journal of Infection and Public Health, Volume 12,
Issue 2, 2019, Pages 285-288, ISSN 1876-0341,
What could be the causes of deterioration?

21. Radiology?
CT chest showed diffuse ground glass attenuation in both
lung bases with focal segmental consolidation in the right
upper lobe that contain small cavity
????
Thamer H. Alenazi, Bashayer S. Alanazi, Abdulrahman Alsaedy, Abdulmoneim Khair, Rifat Solomon, Sameera M. Al Johani, Mycobacterium riyadhense
as the opportunistic infection that lead to HIV diagnosis: A report of 2 cases and literature review, Journal of Infection and Public Health, Volume 12,
Issue 2, 2019, Pages 285-288, ISSN 1876-0341,

22. Grand glass opacification DDx
Ground-glass opacification/opacity (GGO) is a
descriptive term referring to an area of increased
attenuation in the lung on computed tomography (CT) with
preserved bronchial and vascular markings. It is a non-
specific sign with a wide etiology including infection,
chronic interstitial disease and acute alveolar disease.
https://radiopaedia.org/articles/ground-glass-opacification-3

23. Microbiological investigations
• Transtreacheal culture was negative.
• Blood culture was negative
Thamer H. Alenazi, Bashayer S. Alanazi, Abdulrahman Alsaedy, Abdulmoneim Khair, Rifat Solomon, Sameera M. Al Johani, Mycobacterium riyadhense
as the opportunistic infection that lead to HIV diagnosis: A report of 2 cases and literature review, Journal of Infection and Public Health, Volume 12,
Issue 2, 2019, Pages 285-288, ISSN 1876-0341,

24. Case presentaion
• The 2nd & 3rd Sputum for AFB were positive x3,
• Polymerase chain reaction (PCR) for mycobacterium TB (MTB)
complex were negative.
If the treating physician contacted the lab, asked you about this result
What will you respond ?
Thamer H. Alenazi, Bashayer S. Alanazi, Abdulrahman Alsaedy, Abdulmoneim Khair, Rifat Solomon, Sameera M. Al Johani, Mycobacterium riyadhense
as the opportunistic infection that lead to HIV diagnosis: A report of 2 cases and literature review, Journal of Infection and Public Health, Volume 12,
Issue 2, 2019, Pages 285-288, ISSN 1876-0341,

25. ResultNAATSmear
Questionable result:
AFB result due to (NTM)
An inhibitor may be present. A test for inhibitor
may be performed
Low copies number/absent target gene
NegativePositive
References: Updated Guidelines for the Use of Nucleic Acid Amplification Tests in the Diagnosis of Tuberculosis CDC

26. Manual 11ed

27. Case Presentation
• After 4 weeks, growth of both cultures were Mycobacterium
terrae using conventional Biochemical Testing (Nitrate Reduction,
Heat Catalase 68 C, Tellurite Reduction, Urease Production, Tween
80 Hydrolysis, Arylsulfatase, Nacl Tolerance, MacConkey agar
without Crystal Violet and Pigment Production) and INNOLiPA Test
(a line probe assay),
• Furthermore, the specimen was sent for Bioscientia Reference
Laboratory (Ingelheim, Germany) for genotypic testing, where it was
identified as M. riyadhense which was susceptible
to clarithromycin, ethambutol and rifampicin.
Thamer H. Alenazi, Bashayer S. Alanazi, Abdulrahman Alsaedy, Abdulmoneim Khair, Rifat Solomon, Sameera M. Al Johani, Mycobacterium riyadhense
as the opportunistic infection that lead to HIV diagnosis: A report of 2 cases and literature review, Journal of Infection and Public Health, Volume 12,
Issue 2, 2019, Pages 285-288, ISSN 1876-0341,

28. M. Riyadhense ?
D.E. Griffith, T. Aksamit, B.A. Brown-Elliott, A. Catanzaro, C. Daley, F. Gordin, et al.An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases
Am J Respir Crit Care Med, 175 (2007), pp. 367-416,
S. Godreuil, H. Marchandin, A. L. Michon, M. Ponsada, G. Chyderiotis, P. Brisou, et al.Mycobacterium riyadhense pulmonary infection, France and Bahrain .merg Infect
Dis, 18 (2012), pp. 176-178,
Mycobacterium riyadhense (M. riyadhense), a newly recognized slow-growing, non-photochromogenic
NTM. It was originally isolated in 2009 from a 19-year-old male in Riyadh, from where it got its name
It is potentially pathogenic to humans, a claim supported by its close relation
to Mycobacterium szulgai, Mycobacterium kansasii and Mycobacterium malmonese, the most pathogenic
NTM species
Furthermore, it seems to be capable of causing a spectrum of clinical presentations that are clinically
indistinguishable from TB.
Establishing diagnosis of M. riyadhense is challenging since it is not only indistinguishable from TB, but
from other NTM as well. In the patients, the organism was initially misidentified, as M. terrae complex
mandating a high index of suspicion for potential misidentification.

29. M. Riyadhense ?
D.E. Griffith, T. Aksamit, B.A. Brown-Elliott, A. Catanzaro, C. Daley, F. Gordin, et al.An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases
Am J Respir Crit Care Med, 175 (2007), pp. 367-416,
S. Godreuil, H. Marchandin, A. L. Michon, M. Ponsada, G. Chyderiotis, P. Brisou, et al.Mycobacterium riyadhense pulmonary infection, France and Bahrain .merg Infect
Dis, 18 (2012), pp. 176-178,
Most of the reported cases in literature (including our patients) were isolated
from Saudi Arabia few cases from France, Bahrain, Korea have been
documented.
Because of the limited number of cases reported in literature, no specific agent
is approved to treat M. riyadhense infections. Although resistance to isoniazid
was common, several cases reported that nearly all patients have been cured
with Rifampicin, ethambutol, pyrazinamide (first line treatment of −TB)
Duration of treatment varied mainly according to the site of infection. The median
duration of treatment was 13.5 months.

30. NTM pulmonary disaese critieria ?

31. Case Presentation
• Since she presented with symptoms of fever, cough and weight loss,
• Showed a radiologic evidence of pulmonary disease that was not
due to TB, and
• Had at least two sputum specimens positive for AFB thus:
Thamer H. Alenazi, Bashayer S. Alanazi, Abdulrahman Alsaedy, Abdulmoneim Khair, Rifat Solomon, Sameera M. Al Johani, Mycobacterium riyadhense
as the opportunistic infection that lead to HIV diagnosis: A report of 2 cases and literature review, Journal of Infection and Public Health, Volume 12,
Issue 2, 2019, Pages 285-288, ISSN 1876-0341,
Satisfying the diagnostic criteria for NTM lung infections
by the American Thoracic Society and Infectious
Disease Society of America (ATS/IDSA),
She was started on azithromycin, ethambutol
and moxifloxacin for NTM lung infection

32. What further management should be
done?
• HIV screening using 4th generation ELISA was positive and it
was confirmed by a positive western blot test.
• The CD4 count was 29 cells/mcl and HIV viral load was 71,877
copies/ml.
• 2 weeks later was started on combination
of emtricitabine/tenofovir and efavirenz for HIV.
Thamer H. Alenazi, Bashayer S. Alanazi, Abdulrahman Alsaedy, Abdulmoneim Khair, Rifat Solomon, Sameera M. Al Johani, Mycobacterium riyadhense
as the opportunistic infection that lead to HIV diagnosis: A report of 2 cases and literature review, Journal of Infection and Public Health, Volume 12,
Issue 2, 2019, Pages 285-288, ISSN 1876-0341,

33. Duration of treatment
• She completed a course of 12 months of anti-mycobacterial
therapy after which she showed complete resolution of her
chest infection both clinically and radiologically, and her HIV
infection was controlled with suppressed viral load and
improved CD4 count.
Thamer H. Alenazi, Bashayer S. Alanazi, Abdulrahman Alsaedy, Abdulmoneim Khair, Rifat Solomon, Sameera M. Al Johani, Mycobacterium riyadhense
as the opportunistic infection that lead to HIV diagnosis: A report of 2 cases and literature review, Journal of Infection and Public Health, Volume 12,
Issue 2, 2019, Pages 285-288, ISSN 1876-0341,

34. Learning Objective
• Explore the diagnostic criteria of NTM pulmonary diseases
• Interpretations of Mycobacterial investigations

35. CASE 2
Colonization Vs Infection ?

36. Case 2
• 6 years old female in PICU on ventilation due to multiple
congenital anomalies.
• Transtracheal culture has been sent due to increased
respiratory support + fever
ID specialist contacted
you about the growth?

37. Colonization
vs Infection
• Patients in ICUs are subjected to
increased selective pressure and
increased colonization pressure
(uptodate)
David Garner. 2016

38. Sandiumenge, Albertoa
; Rello, Jordib
Ventilator-associated pneumonia caused by ESKAPE organisms: cause, clinical features,
and management, Current Opinion in Pulmonary Medicine: May 2012 - Volume 18 - Issue 3 - p 187-193 doi:
10.1097/MCP.0b013e328351f974

40. • Antibiotic evaluation committees (often involving clinicians,
pharmacists, and microbiologists) whose primary responsibilities are
to promote the effective and safe use of antimicrobial agents, to
evaluate and guide formulary decisions, and to implement
educational programs
• Tasks:
• Develop Protocols and guidelines to promote appropriate antimicrobial
utilization.
• Hospital formulary restrictions of broad-spectrum agents
• Preferential use of narrow-spectrum antibiotics (such as first-generation
cephalosporins and aminoglycosides)

41. MDRO Index
• Risk factors for resistant infections :
• Older age
• Presence of underlying comorbid conditions (eg, diabetes, renal failure,
malignancies, immunosuppression) and higher severity of acute illness
indices
• Long duration of hospitalization
• Frequent encounters with healthcare environments (eg, hemodialysis
units, ambulatory daycare clinics)
• Frequent contact with healthcare personnel concurrently caring for
multiple patients
• Presence of indwelling devices
• Recent surgery or other invasive procedures
• Receipt of antimicrobial therapy, which creates selective pressure
promoting the emergence of multidrug-resistant bacteria

42. References
• Irwin RS, Baumann MH, Bolser DC, et al. Diagnosis and management of cough executive
summary: ACCP evidence-based clinical practice guidelines. Chest 2006; 129: 1S-23S.
• Bajpai T, Shrivastava G, Bhatambare GS, Deshmukh AB, Chitnis V. Microbiological profile of lower
respiratory tract infections in neurological intensive care unit of a tertiary care center from Central
India. Journal of basic and clinical pharmacy. 2013 Jun;4(3):51.
• Oxford Handbook of Infectious Diseases. 2nd ed
• Martin-Loeches I, Povoa P, Rodríguez A, et al. Incidence and prognosis of ventilator-associated
tracheobronchitis (TAVeM): a multicentre, prospective, observational study. Lancet Respir Med
2015; 3: 859–868
• Thamer H. Alenazi, Bashayer S. Alanazi, Abdulrahman Alsaedy, Abdulmoneim Khair, Rifat Solomon,
Sameera M. Al Johani, Mycobacterium riyadhense as the opportunistic infection that lead to HIV
diagnosis: A report of 2 cases and literature review, Journal of Infection and Public Health, Volume
12, Issue 2, 2019, Pages 285-288, ISSN 1876-0341,
• Sandiumenge, Albertoa; Rello, Jordib Ventilator-associated pneumonia caused by ESKAPE
organisms: cause, clinical features, and management, Current Opinion in Pulmonary Medicine: May
2012 - Volume 18 - Issue 3 - p 187-193 doi: 10.1097/MCP.0b013e328351f97
• CAP, HAP, VAP & NTM IDSA Guidelines

43. THANK YOU