Infections in Diabetes - RCSI - PDF

Leading the world to better health Infections in People with Diabetes Mellitus Dr. Rachel Grainger Clinical Lecturer Dept. of Clinical Microbiology, RCSI  RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn...

Leading the world to better health Infections in People with Diabetes Mellitus Dr. Rachel Grainger Clinical Lecturer Dept. of Clinical Microbiology, RCSI  RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn SESSION ID: ENDOBML1 Infections in people with diabetes mellitus Course: Year 2 Lecturer: Dr. Rachel Grainger Date: 29th January 2024 LEARNING OUTCOMES 1. Discuss the epidemiology of infections in people with diabetes mellitus 2. Describe the common infections associated with diabetes mellitus and the most likely causative pathogens 3. Describe the clinical features and complications of the common infections associated with diabetes mellitus 4. Outline the laboratory diagnosis of common infections in people with diabetes mellitus 5. Choose the appropriate antimicrobial agents to treat infections in people with diabetes mellitus 6. Identify the appropriate measures to prevent infection in people with diabetes mellitus 1. DISCUSS THE EPIDEMIOLOGY OF INFECTIONS IN PEOPLE WITH DIABETES MELLITUS DIABETES MELLITUS = Inadequate insulin action Defining manifestation is hyperglycaemia Type 1 diabetes mellitus: Autoimmune destruction of insulin-secreting cells - absolute deficiency of insulin Type 2 diabetes mellitus: Relative inadequacy of insulin action due to end-organ insulin resistance. – 87.9% diabetics in Ireland are Type 2 – Average age of diagnosis is in the 5 to 6th decade of life – Strong family history – Often asymptomatic Parliamentary Question 46154/21 September 28th answer in writing October 15th 2021 available at https://www.oireachtas.ie/en/debates/question/2021-09-28/661/?highlight%5B0%5D=46154&highlight%5B1%5D=21 DIABETES AND INFECTION Type 1 and type 2 Diabetes Mellitus associated with high risk of infection. – 6% of infection-related hospitalizations – 12% of infection-related deaths – strongest associations with bone and joint infections, sepsis and cellulitis Infections in Diabetes – more frequent – poorer response to therapy – more rapid progression to severe forms of infection Good evidence that reduction of hyperglycaemia can improve outcomes. Carey IM, Critchley JA, DeWilde S, Harris T, Hosking FJ, Cook DG. Risk of Infection in Type 1 and Type 2 Diabetes Compared With the General Population: A Matched Cohort Study. Diabetes Care. 2018;41(3):513–521.  Disruption of the immune system in diabetes, both T1 and T2 It affects: – Innate immunity – Adaptive immunity – Cytokine signalling Microvascular complications such as neuropathy = > susceptibility to an accidental lesions in the barrier of the skin, one of the first lines of defence. Poor vascular flow to sites of infection = > compromise an appropriate immune response and healing > worsening or secondary infections. Forbes J.M., Cooper M.E. Mechanisms of diabetic complications. Physiological Reviews. 2013;93(1):137–188. 2. DESCRIBE THE COMMON INFECTIONS ASSOCIATED WITH DIABETES MELLITUS AND THE MOST LIKELY CAUSATIVE PATHOGENS 3. DESCRIBE THE CLINICAL FEATURES AND COMPLICATIONS OF THESE COMMON INFECTIONS WHAT COMMON INFECTIONS ARE ASSOCIATED WITH DIABETES?  *REGUB: Refer to UTI URINARY TRACT INFECTIONS IN DIABETES Lecture for more detail Most common organisms: E. coli, Enterococci Women with DM are almost twice as likely to suffer from UTI Urine culture is strongly recommended Treatment: Do not treat asymptomatic bacturia Antibiotic decisions: based on local antibiotic resistance trends. Refer to local guidelines. Clinical features of UTI: Complications: Dysuria Incontinence Nocturia Chronic prostatitis Haematura Staghorn urinary calculi Fever Pyelonephritis Complications: Patients with DM have a higher risk of progression to pyelonephritis which is more severe and often bilateral Edward J. Boyko, Stephan D. Fihn, Delia Scholes, Linn Abraham, Barbara Monsey, Risk of Urinary Tract Infection and Asymptomatic Bacteriuria among Diabetic an d Nondiabetic Postmenopausal Women, American Journal of Epidemiology, Volume 161, Issue 6, 15 March 2005, Pages 557–564 WHAT IS THE MOST COMMON CAUSATIVE PATHOGEN IN PNEUMONIA? A. Staphylococcus aureus B. Klebsiella pneumoniae C. Streptococcus pneumonia D. All of the above  *Refer to LRTI Lecture RESPIRATORY INFECTIONS IN DIABETES for more detail Pneumonia Patients with DM have higher rates of hospitalization and mortality Most common organisms: Streptococcus species (commonest causes of community-acquired pneumonia) Gram negative anaerobes (common cause of aspiration pneumonia) Treatment: Community-acquired pneumonia: calculate CURB-65 for antibiotics – 0-1: Mild Oral amoxicillin or clarithromycin or doxycycline – 2: Moderate IV amoxicillin + oral clarithromycin – 3-5: Severe IV co- amoxiclav + oral clarithromycin Healthcare-acquired pneumonia: Antibiotic decisions: based on local antibiotic resistance trends. Refer to local guidelines. PNEUMONIA Clinical Features Productive cough – mucopurulent sputum Shortness of breath Pleuritic chest pain Fatigue Malaise Fever Complications Empyema Pericarditis Respiratory failure Diabetic Ketoacidosis Sepsis RESPIRATORY INFECTIONS IN DIABETES Tuberculosis Higher risk of contracting with poorer glycaemic control Higher risk of treatment failure Isoniazid needs to be taken with pyridoxine to prevent neuropathy Rifampin can cause hyperglycaemia and also induces cyp450 leading to increased clearance of various DM agents  COVID-19 Appears to be an association between DM and COVID-19 Type 1 and type 2 DM are now known to be important risk factors for morbidity and mortality with the disease. (3) There is evidence that poorly-controlled DM as compared with well-controlled DM results in significantly increased mortality in both type 1 Abu-Farha, M., Al-Mulla, F., Thanaraj, T. A., Kavalakatt, S., Ali, H., Ghani, M., & and type 2 DM. Abubaker, J. (2020). Impact of Diabetes in Patients Diagnosed With COVID-19. Frontiers in Immunology Lim S, Bae JH, Kwon HS, Nauck MA. COVID-19 and diabetes mellitus: from pathophysiology to clinical management. Nat Rev Endocrinol. 2021;17(1):11–30.  *Refer to SSTI Lecture SKIN AND SOFT TISSUE INFECTION (SSTI) for more detail CELLULITIS/WOUND INFECTION Most common SSTI in diabetes Most common organisms: S. aureus, S. pyogenes and other Strep species Treatment: – Start smart (Empiric) - flucloxacillin (covers S. aureus, S. pyogenes ) – Then focus (Directed) – based on culture & susceptibilities, e.g. change to benzylpenicillin if S. pyogenes confirmed) MRSA : IV vancomycin Clinical features: Red, swollen, and painful area of skin that is warm and tender to the touch Fever and rigours Blisters Skin dimpling SKIN AND SOFT TISSUE INFECTION (SSTI) Fournier Gangrene Most common organisms: Anaerobic and aerobic bacteria such as Staph aureus, Pseudomonas and Clostridium perfringens Treatment: Debridement essential Broad-spectrum antibiotics Clinical features: Infection of soft tissue and fascia Pain Fever, diarrhoea, dizziness, general malaise Swelling, purplish rash Necrosis, oedema  SKIN AND SOFT TISSUE INFECTION (SSTI) Necrotising Fasciitis SEVERE infection, rapidly progressive, limb loss seen more often Most common organisms: Group A strep (Streptococcus pyogenes), often polymicrobial Treatment: Surgical debridement Start smart: Broad-spectrum empiric therapy e.g. vancomycin + piperacillin-tazobactam + clindamycin Then focus: If group A strep: benzylpenicillin + clindamycin (suppresses toxin production) Clinical features: Rapidly progressive necrotising fasciitis of external genitalia, perineum and perianal region Severe genital pain, cyanosis, erythema Wet gangrene with faeculent odour (aerobic)  GASTROINTESTINAL INFECTIONS IN DIABETES Hepatitis 33% of chronic hepatitis C patients have T2D NAFLD more common in T2DM Hepatitis C outcomes worse with more frequent cirrhosis and failure of antivirals Clinical features: Complications: Abdominal pain Cirrhosis Nausea and vomiting Malignancy Weakness and fatigue Fulminant liver failure Dark urine Knobler H, Schihmanter R, Zifroni A, Fenakel G, Schattner A. Increased risk of type 2 diabetes in noncirrhotic patients with chronic hepatitis C virus infection. Mayo Clin Proc (2000) 75(4):355– 9. 10.4065/75.4.355 Diabetes Liver Screen Initiative 2017. Diabetes Ireland and Professor Suzanne Norris (St James’s Hospital and Liver Wellness®).  GASTROINTESTINAL INFECTIONS IN DIABETES Emphysematous Cholecystitis 50% of patients have DM Most common organisms: Clostridium perfringens, Klebsiella and E. coli Treatment is typically cholecystectomy but antibiotics can be trialed in mild cases Clinical features: Complications: Nonspecific AKI (acute kidney injury) Fevers Septic shock Abdominal pain Rarely pneumnomediastinum Nausea and vomiting Knobler H, Schihmanter R, Zifroni A, Fenakel G, Schattner A. Increased risk of type 2 diabetes in noncirrhotic patients with chronic hepatitis C virus infection. Mayo Clin Proc (2000) 75(4):355–9. 10.4065/75.4.355 Diabetes Liver Screen Initiative 2017. Diabetes Ireland and Professor Suzanne Norris (St James’s Hospital and Liver Wellness®).  HEAD AND NECK INFECTIONS IN DIABETES Necrotizing Otitis Externa 90% of cases are diabetic DM have a higher risk of abscess formation requiring draining Vascular compromise and pseudomonal vasculitis much more commonly seen in DM Most common organisms: Pseudomonas aeruginosa Treatment: Systemic antibiotics with antipseudomonal action Local therapy to the canal including cleaning/debridement Complications: Clinical features: Invasion of surrounding structures – facial Persistent and severe, deep-seated nerve ear pain (often worse at night) Skull base osteomyelitis Foul smelling purulent otorrhea Intracranial involvement – confusion, Headaches meningitis, thrombosis, death Hasnaoui M, Ben Mabrouk A, Chelli J, Larbi Ammari F, Lahmar R, Toumi A, Mighri K. Necrotising otitis externa: A single centre experience. J Otol. 2021 Jan;16(1):22-26. doi: 10.1016/j.joto.2020.07.005. Epub 2020 Jul 29. PMID: 33505446;  FUNGAL INFECTIONS IN DIABETES Onychomycosis Twice as likely to develop in patients with DM Potentially up to 1/3 of all patients with DM impacted Diagnosis Based on fungal culture/microscopy Treatment Oral agents most effective Clinical features: Complications: Discolouration Functional limitations Subungal hyperkeratosis Chronic pain Onycholysis Cellulitis Nail plate destruction Trovato L, Calvo M, De Pasquale R, Scalia G, Oliveri S. Prevalence of Onychomycosis in Diabetic Patients: A Case-Control Study Performed at University Hospital Policlinico in Catania. J Fungi (Basel). 2022;8(9):922. Published 2022 Aug 30. doi:10.3390/jof8090922  FUNGAL INFECTIONS IN DIABETES Mucormycosis 17-88% cases diabetic Causative organisms: mucormycetes Diagnosis: Tissue biopsy needed and imaging helpful to identify extent of infection Treatment Debulking of infection Adjuvant antifungal therapy Clinical features (depends on site): Most commonly sinus +/- cerebrum/orbits: acute sinusitis and headache Respiratory tract (second most common : fever, haemoptysis Skin (third most common): ulcerative necrotic lesion: single, painful indurated area of cellulitis GI: abdo pain, haematemesis Prakash, H., & Chakrabarti, A. (2019). Global Epidemiology of Mucormycosis. Journal of Fungi, 5(1), 26.  FUNGAL INFECTIONS IN DIABETES Genitourinary Risk increased with SGLT2 inhibitors and higher concentration of glucose in urine Complement evasion is facilitated by binding complement factor H Communicate with micro lab that Candida species is suspected Most common organisms: Candida species Treatment If symptomatic, then fluconazole first line Complications: Clinical features: Recurrence Pruritis Candidaemia in immunocompromised patients Pain Vaginal discharge Dyspareunia Rodrigues CF, Rodrigues ME, Henriques M. Candida sp. Infections in Patients with Diabetes Mellitus. J Clin Med. 2019;8(1):76. Published 2019 Jan 10. doi:10.3390/jcm8010076 4. OUTLINE THE LABORATORY DIAGNOSIS OF COMMON INFECTIONS IN PEOPLE WITH DIABETES MELLITUS WHAT INVESTIGATIONS WOULD YOU DO?  INVESTIGATIONS FOR INFECTION BLOOD TESTs RADIOLOGY VASCULAR NEUROPATHIC ASSESSMENT Blood cultures CXR if pneumonia suspected Ankle brachial index Clinical examination Other cultures Plain X-ray of the joint or Doppler waveform Nerve conduction depending on the site affected foot Transcutaneous oxygen studies of infection (e.g., MRI of the foot or bone tension where available MRI spine where urine / tissue / bone) scan: If osteomyelitis not Toe pressures appropriate MRSA screen evident on plain X-ray Vascular consult - Previous MRSA - Plain X-ray may be - Recent hospitalisation, normal in the early stages - Admitted from of osteomyelitis. residential care - It may take 14 days - Surgical site infection before osteomyelitis apparent. Other investigations (e.g., FBC / CRP / HbA1c / - MRI is more sensitive at Capillary glucose monitoring detecting early changes of Ketones / pH VBG) osteomyelitis  URINE SAMPLES Usual container Urine container with boric acid Void first 5mls Collect MIDSTREAM urine into sterile container Get to the lab ideally within 2 hours of collection Use the boric acid container if there is going to be a delay of ≥4 hours between collection & transport to laboratory – Prevents overgrowth of bacteria in the sample FOOT INFECTION IN DIABETES IMPORTANT: SEND APPROPRIATELY OBTAINED SPECIMENS TO MICROBIOLOGY, IDEALLY BEFORE STARTING ANTIMICROBIAL THERAPY Specimens best taken by podiatrist – Cleanse and debride wound first – Obtain tissue specimen from the base of debrided ulcer Avoid superficial swabs – less accurate results, likely colonising flora Scrapings with sterile scalpel Aspirate of purulent secretions Bone biopsy if bone involvement – gold standard for diagnosing osteomyelitis – Place specimen in normal saline in a specimen container and send promptly to microbiology. – Must provide clinical details that the specimen is from a diabetic foot infection – Ask for Gram stain, culture and susceptibility testing. FROM PATIENT TO PATHOGEN ID https://www.youtube.com/watch?v=-DDI5nEjgrE  PROBE TO BONE TEST AND INTERPRETING SWABS Probe to bone test can be useful in aiding diagnosis of osteomyelitis. Remember, a swab from an ulcer will nearly always grow something (sometimes 4 or 5 organisms), whether it is infected or not. Results need to be interpreted within the broader clinical context. REVISED GUIDELINES ON DIABETIC FOOT INFECTION (DFI) 2012 Clinical Diagnosis of Infection 1. Patient as a whole − Systemic signs 2. Affected limb − Risk factors 3. Affected wound – Presence of at least 2 of classic symptoms or signs of inflammation or purulence 5. CHOOSE THE APPROPRIATE ANTIMICROBIAL AGENTS TO TREAT INFECTIONS IN PEOPLE WITH DIABETES MELLITUS START SMART: CHOOSING EMPIRIC ANTIBIOTICS Hospital guidelines – Always consult your local hospital guidelines THINK CAPPA 1. Clinical assessment: – What is likely site of infection? 2. Acquisition: – Is it community, healthcare or hospital-acquired? – Was the hospital outside Ireland? – Local factors e.g. antibiotic resistance rates 3. Previous antibiotics 4. Previous microbiology results 5. Allergy, is there a history?  Where has the patient come from or are they in hospital > 48 hours? (i.e., from home/nursing home/other hospital etc) Previous antibiotics (including from GP/other hospitals) 1. Patient History History of antibiotic allergy (rash vs. anaphylaxis) Recent hospital admissions (including hospitals abroad) Presence of prosthetic material (joints / valves etc) Antibiotic resistant organism in the past (eg MRSA) 2. What is the likely site of Respiratory / Urinary / Skin and soft tissue / intra-abdominal / IV line /related to recent procedure (eg wound) etc infection? If diarrhoea could this be C. difficile? 2. Is source control Drain abscess / remove prosthetic material etc required? Maybe 4. Positive microbiology Check laboratory IT for colonisation/infection with antibiotic from previous admissions? resistant organisms. Eg MRSA / ESBL+ / VRE 5. Do I need a bactericidal Eg meningitis / endocarditis antibiotic? HOW DO WE MANAGE DIABETIC FOOT INFECTIONS? General Principles: Spectrum of infections: – Cellulitis only, Localised paronychia (nail bed infection). – Skin or soft-tissue infection in the vicinity of a DM foot ulcer (mild, moderate, severe). – Bone or joint infection (osteomyelitis or septic arthritis) in the vicinity of an ulcer. Empiric therapy should be chosen based on severity and likely pathogens. Optimise glycaemic control Debridement, dressing, offloading (removing weight from affected area) HOW DO WE DETERMINE HOW SEVERE THE INFECTION IS? CLASSIFICATION OF CELLULITIS SEVERITY Mild – Local infection involving skin and subcutaneous tissue only – Erythema around ulcer: >0.5cm 2cm 90 beats/min – RR > 20 breaths/min or PaCO2 < 32mmHg – WCC >12 000/ < 4 000 cells/μL – Presence of ischaemia i.e. LOCAL INFECTION WITH SIGNS OF SIRS Guidelines on the diagnosis and treatment of foot infection in persons with diabetes (IWGDF 2019 update) GENERAL PRINCIPLES OF ANTIMICROBIALS FOR CELLULITIS / OSTEOMYELITIS Mild to moderate: Gram positive cocci is usually sufficient Usually don’t need to cover Pseudomonas aeruginosa is unless the patient has risk factors e.g., prior history, recent antibiotics, inpatient. Severe infections: Broad spectrum empiric therapy pending culture results Urgent surgical review if gas in deeper tissues, abscess or necrotizing fasciitis. Suspected osteomyelitis: Broad spectrum empiric therapy pending culture results (tissue/bone biopsy, preferably if possible) Surgical review for wounds with substantial non-viable tissue or extensive bone /joint involvement. ANTIMICROBIAL TREATMENT Cellulitis without a foot ulcer (Most likely staph or strep) Mild or Moderate – Start smart (Empiric) - flucloxacillin (covers Staph. aureus & Strep. pyogenes) but consider MRSA risk factors – Then focus (Directed) – based on culture & susceptibilities, e.g. change to benzylpenicillin if S. pyogenes confirmed) Severe – IV Flucloxacillin x 7 days – Known MRSA colonisation or risk factors for MRSA colonisation: IV Vancomycin ANTIMICROBIAL TREATMENT Superficial foot ulcer – Empiric: PO flucloxacillin (covers Staph. aureus & Strep. pyogenes) Deep foot ulcer requiring admission – Anaerobic coverage needed – Deeper foot ulcers are more likely to be polymicrobial – IV Co-amoxiclav or – Piperacillin-tazobactam (sepsis or concern for Pseudomonas infection) – If concern for MRSA, add Vancomycin DEEP FOOT ULCER REQUIRING ADMISSION Osteomyelitis Empiric treatment: Co-amoxiclav or Piperacillin-tazobactam Similar to treating a deep ulcer with systemic involvement. Needs at least 28 days duration but may need longer depending on clinical presentation, extent of tissue involvement, adequate debridement and vascular supply. 6. IDENTIFY THE APPROPRIATE MEASURES TO PREVENT INFECTION IN PEOPLE WITH DIABETES MELLITUS NON-MEDICAL INTERVENTIONS - LIFESTYLE Physical activity – associated with improvement in the immune system which are known to extend as well to those with DM. Smoking cessation Hygiene – Diabetic patients should wash their hands regularly, keep their skin clean and dry, and avoid sharing personal items such as towels or razors to reduce their risk of infection. Maintain a healthy diet: – A healthy diet that is rich in fruits, vegetables, and whole grains can help boost the immune system and reduce the risk of infections. FOOT CARE Foot self inspection/examination, correct footwear expert foot care - attending a podiatrist regularly, care for wounds promptly and properly – e.g. offloading) There are five key elements that underpin efforts to prevent foot ulcers: 1. Identifying the at-risk foot 2. Regularly inspecting and examining the at-risk foot 3. Educating the patient, family and healthcare professionals 4. Ensuring routine wearing of appropriate footwear 5. Treating risk factors for ulceration (as per IWGDF Practical guidelines on the prevention and management of diabetic foot disease, very useful resource) AREAS OF THE FOOT AT HIGHEST RISK FOR ULCERATION OTHER MEDICAL PREVENTION MEASURES Glucose control Manage other medical conditions: – Diabetic patients should also manage any other medical conditions they have, such as cardiovascular disease or hypertension, as these conditions can weaken the immune system and increase the risk of infections. Get vaccinated: – Diabetic patients should get vaccinated against infections such as COVID- 19, influenza and S. pneumoniae, as these infections can be more severe in people with diabetes. GLUCOSE CONTROL Glycaemic control is correlated with infection. – One study found that lower glucose in the first 2 days postoperatively was associated with a decrease in deep wound infection. Insulin has been suggested to have a protective effect against infection risk in those with DM. T cells which lack insulin receptor are impaired Chemotaxis in PMNs are impaired in DM which is restored with glucose and insulin There are some suggestions that therapies beyond insulin can have an immune-restorative effect, such as metformin. Thought to increase both number and function of immune cells. Zerr KJ, Furnary AP, Grunkemeier GL, Bookin S, Kanhere V, Starr A. Glucose control lowers the risk of wound infection in diabetics after open heart operations. Ann Thorac Surg. 1997;63(2):356–61.  1 2 3 4 5 6 7 8 A 64 year old male with a 10 year history of type 2 3 diabetes mellitus presents to the diabetic day centre PLANNING MANAGEMENT complaining of increased pain and discharge from an ulcer on the sole of his right foot. He is reviewed by the podiatrist who debrides the ulcer and takes a deep tissue specimen which is sent for culture and susceptibility testing. The patient is reviewed by the endocrinology registrar who notes that he is systemically well however there is some mild erythema approximately 0.5 cm surrounding the ulcer. There are no previous microbiology results for the patient and he has no allergies.  1 2 3 4 5 6 7 8 A. Incorrect, there is no history of 3 penicillin allergy PLANNING MANAGEMENT B. Incorrect, flucloxacillin is the most appropriate antibiotic but the maximum dose that can be What is the most appropriate given orally is 1g QDS management for this patient? C. Correct, the patient has a mild infection is not systemically unwell so does not require IV A. Doxycycline 200mg OD PO antibiotics B. Flucloxacillin 2g QDS PO D. Incorrect, the patient has a mild infection is not systemically C. Flucloxacillin 500mg QDS PO unwell so does not require IV D. Piperacillin tazobactam 4.5g antibiotics, he also does not have TDS IV a history of pseudomonas E. Incorrect, the patient has a mild E. Vancomycin 1g BD IV infection is not systemically unwell so does not require IV antibiotics, he also does not have a history of MRSA or penicillin allergy R CS I LEAD IN G TH E WORLD TO BETT ER H EALT H Clic k t o ed it ma st er t itle st yle Thank you Click to edit master title style Pr es ent er Name Tit le , De p ar tme n t, RCSI