Microbiology Nuts & Bolts Opportunistic infections

1. Microbiology Nuts & BoltsOpportunistic infections Dr David Garner Consultant Microbiologist Frimley Park Hospital NHS Foundation Trust

2. Aims & Objectives To understand the difference between sepsis with neutropaenia and neutropaenic sepsis To know how to manage neutropaenic sepsis To be aware of the types of immunodeficiency syndromes To understand what an opportunistic infection is To consider opportunist infections in HIV infection

3. Geoff 43 year old On chemotherapy for malignant melanoma Presents with shortness of breath On examination Temperature 39.5 oC Crackles throughout precordium Heart Rate 120bpm B.P. 120/75 How should Geoff be managed?

4. Differential Diagnosis • Immediately life-threatening • Common • Uncommon • Examination and investigations explore the differential diagnosis • What would be your differential diagnosis for Geoff?

5. Differential Diagnosis • Immediately life-threatening • Severe sepsis or neutropaenic sepsis, pulmonary embolus, myocardial infarction, meningitis, encephalitis, cholangitis… • Common • Urinary tract infection (UTI), community acquired pneumonia (CAP), cellulitis, cholecystitis, URTI, gastroenteritis, etc., etc… • Uncommon • Opportunistic infection… • How would you investigate this differential diagnosis?

6. Full history and examination Bloods FBC, CRP, U&Es Lactate Blood Cultures Urine Dipstick? MSU Chest X-ray

7. Geoff Bloods WBC 0.1 x 109/L CRP 113 Lactate 3.5mmol/L U&Es – Urea 17, Creat 196 Urine Dipstick -leucs, -nitrites Microscopy <10 x106 WBC, no epithelial cells

8. What is the diagnosis? • How would you manage Geoff now? • What is neutropaenic sepsis? • What are the common bacterial causes of neutropaenic sepsis?

9. Sepsis Definitions • Sepsis: clinical evidence of infection plus evidence of systemic response to infection • Sepsis syndrome: sepsis plus evidence of altered organ perfusion • Severe sepsis: sepsis associated with organ dysfunction, hypoperfusion or hypotension For every hour delay in treatment mortality increases by 7% up to 6 hours (42%)

10. Culture: classification of bacteria Causes of sepsis can originate in any body organ…

11. Neutropaenic sepsis • Sepsis in a patient who was neutropaenic BEFORE becoming septic • Neutrophils < 0.5 x 109 PLUS temperature > 39oC once or >38 oC twice • Need bactericidal antibiotics specifically targeted against Gram-negative bacteria and Staphylococcus aureus • Antibiotics should be administered within 1 hour • If possible try to take blood cultures before antibiotics but DO NOT delay antibiotics unnecessarily - Medical emergency • Empirical treatment when source unknown NOT treatment when source known e.g. Community Acquired Pneumonia

13. Opportunist infection • An infection with a microorganism that wouldn’t normally cause an infection in a patient with a normal immune system • Can be: • New microorganism exploiting the lack of immune response • Latent microorganism escaping control of the immune response • Can be bacterial, viral, fungal or parasitic

14. Fungi • Yeast vs. mould • Candida spp. • Esp. C krusei & C. glabrata • Aspergillus spp. • Esp. A fumigatus • Mucor • Investigation • Culture • Histology • Beta-d-glucan • Galactomannan

15. Viruses • Post bone marrow transplant • Months – years after! • Severe pneumonitis • High mortality • Viruses • Respiratory syncytial virus • Adenovirus • Influenza • Parainfluenza

16. Geoff 3 days later WBC increasing Pain at site of CVC What is the diagnosis? How would you manage Geoff? Line removed Started IV teicoplanin Made a full recovery

17. Types of IV Device • Peripheral Venous Catheter • Peripheral Arterial Catheter • Short-term Central Venous Catheter (CVC) • Peripherally Inserted Central Catheter (PICC) • Long-term Central Venous Catheter (CVC) e.g. Broviac, Groshong, Hickman catheters • Totally Implanted Catheter • Pacemaker, cardioverter defibrillator • IVC filters • Prosthetic vascular grafts

18. IV Device Infections • Treatment • Targeted at Gram-positive bacteria e.g. Staphylococcus aureus • In immunosuppressed patients additional cover given for Gram-negative bacteria e.g. Pseudomonas aeruginosa, Klebsiella pneumoniae • Usually IV Vancomycin OR IV Teicoplanin PLUS IV Gentamicin • Remove the infected device!

19. Immunodeficiency states • Primary • Antibody deficiency • T cell deficiency • Secondary • Viral • Drugs • Haematological malignancy • Metabolic • Immunoglobulin loss • Other e.g. splenectomy, percutaneous devices, etc.

20. Viral - HIV • Human Immunodeficiency Virus causes gradual loss of CD4 T cells leading to immunodeficiency • Acquired Immune Deficiency Syndrome (AIDS) = group of opportunistic infections which only occur with profound reduction in immune function

21. AIDS

22. AIDS

23. Acute Retroviral Illness • Acute retroviral syndrome 2-3 weeks after acquisition of HIV (aka seroconversion illness) • Fever • Lymphadenopathy • Pharyngitis • Rash • Myalgia • Diarrhoea • Headache • Nausea and vomiting

25. Kaposi Sarcoma • Tumour caused by HHV8 • Can be: • Cutaneous • Mucosal • Visceral • Treatment • Surgery • Cryotherapy • Intralesional injections e.g. vinblastine • Topical e.g. alitreninoin • Systemic chemotherapy • HAART

26. Pneumocystis jirovecii • Still known as PCP = pneumocystis pneumonia • Most common respiratory infection in AIDS • By 2 years old >85% colonized with P. jirovecii • P. jirovecii = fungus • Ground glass shadowing • Profound hypoxia on minimal exertion

27. 1st line – 21 days • Co-trimoxazole (Septrin) 120mg/kg/day in 2-4 divided doses PLUS • Prednisolone 40mg BD (weaning course over 21 days) • 2nd line – 21 days • Clindamycin 600mg QDS PLUS • Primaquine 30mg OD (beware G6PD) PLUS • Prednisolone 40mg BD (weaning course over 21 days) • Start HAART at 2 weeks

28. Cryptococcus neoformans • Fungus found in soil • Possible association with pigeons (gut flora?) • Causes disseminated infection including meningoencephalitis • Worldwide approx. 1,000,000 cases/year  600,000 deaths

29. Presentation • Slow onset (1-2 weeks) fever, malaise, headache • 25% photophobia, neck stiffness, vomiting, confusion • Occasionally cough, shortness of breath, neurological defects and rash (similar to molluscum contagiosum)

30. Investigations • Serum for cryptococcal antigen (CrAg) • CSF • Slightly raised polymorph count (<50 cells/mL) • Raised protein, low glucose • Raised intracranial pressure • India ink • CSF CrAg

31. Induction ≥ 2 weeks • IV Liposomal Amphotericin B 3-4mg/kg/day PLUS • PO Flucytosine 25mg/kg QDS (or Fluconazole 800mg OD) • Consolidation 8 weeks • PO Fluconazole 400mg OD • Maintenance ≥ 1 year • PO Fluconazole 200mg OD • HAART 2-10 weeks after starting treatment • Monitor CD4 and serum CrAg lifelong

32. Cytomegalovirus • HHV 5 • Latent infection • Reactivates in immunosuppression • Can cause: • Retinitis • Pneumonitis • Colitis • Meningoencephalitis • Peripheral neuropathy

34. 1st Line • IV Ganciclovir • 2nd Line • IV Foscarnet • Increasing role for PO Valganciclovir

35. Conclusions • Neutropaenic sepsis is sepsis that occurs in patients who are neutropaenic before septic • Neutropaenic sepsis is a medical emergency • Opportunistic infections are infections that would not occur in immunocompetent patients • Secondary infections in HIV relate to the CD4 count • Immunosuppressed patients with infections need regular assessment until the underlying infection declares itself

36. Any Questions?