Microbiology Nuts Bolts Opportunistic infections Dr David Garner

  • Slides: 36
Download presentation
Microbiology Nuts & Bolts Opportunistic infections Dr David Garner Consultant Microbiologist Frimley Park Hospital

Microbiology Nuts & Bolts Opportunistic infections Dr David Garner Consultant Microbiologist Frimley Park Hospital NHS Foundation Trust www. microbiologynutsandbolts. co. uk

Aims & Objectives • To understand the difference between sepsis with neutropaenia and neutropaenic

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 www. microbiologynutsandbolts. co. uk

Geoff • • 43 year old On chemotherapy for malignant melanoma Presents with shortness

Geoff • • 43 year old On chemotherapy for malignant melanoma Presents with shortness of breath On examination – – Temperature 39. 5 o. C Crackles throughout precordium Heart Rate 120 bpm B. P. 120/75 • How should Geoff be managed? www. microbiologynutsandbolts. co. uk

Differential Diagnosis • Immediately life-threatening • Common • Uncommon • Examination and investigations explore

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

Differential Diagnosis • Immediately life-threatening – Severe sepsis or neutropaenic sepsis, pulmonary embolus, myocardial

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… • Uncommon – Opportunistic infection… • How would you investigate this differential diagnosis? www. microbiologynutsandbolts. co. uk

 • Full history and examination • Bloods – FBC, CRP, U&Es – Lactate

• Full history and examination • Bloods – FBC, CRP, U&Es – Lactate – Blood Cultures • Urine – Dipstick? – MSU • Chest X-ray www. microbiologynutsandbolts. co. uk

Geoff • Bloods – – WBC 0. 1 x 109/L CRP 113 Lactate 3.

Geoff • Bloods – – WBC 0. 1 x 109/L CRP 113 Lactate 3. 5 mmol/L U&Es – Urea 17, Creat 196 • Urine – Dipstick -leucs, -nitrites – Microscopy <10 x 106 WBC, no epithelial cells www. microbiologynutsandbolts. co. uk

 • • What is the diagnosis? How would you manage Geoff now? What

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

Sepsis Definitions • Sepsis: clinical evidence of infection plus evidence of systemic response to

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

Culture: classification of bacteria Gram’s Stain Positive Cocci No Stain Uptake Negative Bacilli Cocci

Culture: classification of bacteria Gram’s Stain Positive Cocci No Stain Uptake Negative Bacilli Cocci Bacilli Acid Fast Bacilli Non-culturable Causes of sepsis can originate in any bodywww. microbiologynutsandbolts. co. uk organ…

Neutropaenic sepsis • Sepsis in a patient who was neutropaenic BEFORE becoming septic •

Neutropaenic sepsis • Sepsis in a patient who was neutropaenic BEFORE becoming septic • Neutrophils < 0. 5 x 109 PLUS temperature > 39 o. C once or >38 o. C 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 www. microbiologynutsandbolts. co. uk

www. microbiologynutsandbolts. co. uk

www. microbiologynutsandbolts. co. uk

Opportunist infection • An infection with a microorganism that wouldn’t normally cause an infection

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 www. microbiologynutsandbolts. co. uk

Fungi • Yeast vs. mould • Candida spp. – Esp. C krusei & C.

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

Viruses • Post bone marrow transplant – Months – years after! • Severe pneumonitis

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

Geoff • 3 days later • WBC increasing • Pain at site of CVC

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 www. microbiologynutsandbolts. co. uk

Types of IV Device • • • Peripheral Venous Catheter Peripheral Arterial Catheter Short-term

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 www. microbiologynutsandbolts. co. uk

IV Device Infections • Treatment – Targeted at Gram-positive bacteria e. g. Staphylococcus aureus

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! www. microbiologynutsandbolts. co. uk

Immunodeficiency states • Primary – Antibody deficiency – T cell deficiency • Secondary –

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

Viral - HIV • Human Immunodeficiency Virus causes gradual loss of CD 4 T

Viral - HIV • Human Immunodeficiency Virus causes gradual loss of CD 4 T cells leading to immunodeficiency • Acquired Immune Deficiency Syndrome (AIDS) = group of opportunistic infections which only occur with profound reduction in immune function www. microbiologynutsandbolts. co. uk

AIDS www. microbiologynutsandbolts. co. uk

AIDS www. microbiologynutsandbolts. co. uk

AIDS www. microbiologynutsandbolts. co. uk

AIDS www. microbiologynutsandbolts. co. uk

Acute Retroviral Illness • Acute retroviral syndrome 2 -3 weeks after acquisition of HIV

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 www. microbiologynutsandbolts. co. uk

www. microbiologynutsandbolts. co. uk

www. microbiologynutsandbolts. co. uk

Kaposi Sarcoma • Tumour caused by HHV 8 • Can be: – Cutaneous –

Kaposi Sarcoma • Tumour caused by HHV 8 • Can be: – Cutaneous – Mucosal – Visceral • Treatment – Surgery – Cryotherapy – Intralesional injections e. g. vinblastine – Topical e. g. alitreninoin – Systemic chemotherapy – HAART www. microbiologynutsandbolts. co. uk

Pneumocystis jirovecii • Still known as PCP = pneumocystis pneumonia • Most common respiratory

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 www. microbiologynutsandbolts. co. uk

 • 1 st line – 21 days – Co-trimoxazole (Septrin) 120 mg/kg/day in

• 1 st line – 21 days – Co-trimoxazole (Septrin) 120 mg/kg/day in 2 -4 divided doses PLUS – Prednisolone 40 mg BD (weaning course over 21 days) • 2 nd line – 21 days – Clindamycin 600 mg QDS PLUS – Primaquine 30 mg OD (beware G 6 PD) PLUS – Prednisolone 40 mg BD (weaning course over 21 days) • Start HAART at 2 weeks www. microbiologynutsandbolts. co. uk

Cryptococcus neoformans • Fungus found in soil • Possible association with pigeons (gut flora?

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

 • Presentation – Slow onset (1 -2 weeks) fever, malaise, headache – 25%

• 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) www. microbiologynutsandbolts. co. uk

 • Investigations – Serum for cryptococcal antigen (Cr. Ag) – CSF • Slightly

• Investigations – Serum for cryptococcal antigen (Cr. Ag) – CSF • Slightly raised polymorph count (<50 cells/m. L) • Raised protein, low glucose • Raised intracranial pressure • India ink • CSF Cr. Ag www. microbiologynutsandbolts. co. uk

 • Induction ≥ 2 weeks – IV Liposomal Amphotericin B 3 -4 mg/kg/day

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

Cytomegalovirus • • HHV 5 Latent infection Reactivates in immunosuppression Can cause: – –

Cytomegalovirus • • HHV 5 Latent infection Reactivates in immunosuppression Can cause: – – – Retinitis Pneumonitis Colitis Meningoencephalitis Peripheral neuropathy www. microbiologynutsandbolts. co. uk

www. microbiologynutsandbolts. co. uk

www. microbiologynutsandbolts. co. uk

 • 1 st Line – IV Ganciclovir • 2 nd Line – IV

• 1 st Line – IV Ganciclovir • 2 nd Line – IV Foscarnet • Increasing role for PO Valganciclovir www. microbiologynutsandbolts. co. uk

Conclusions • Neutropaenic sepsis is sepsis that occurs in patients who are neutropaenic before

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 CD 4 count • Immunosuppressed patients with infections need regular assessment until the underlying infection declares itself www. microbiologynutsandbolts. co. uk

Any Questions? www. microbiologynutsandbolts. co. uk

Any Questions? www. microbiologynutsandbolts. co. uk