CNS Infections, PUO and Superbugs 2024-25 PDF

MSOP1004 Infections-Central Nervous System Infections - Pyrexia of Unknown Origin Dr Veronica Chorro-Mari Consultant Pharmacist East Kent University Hospitals NHS Foundation Trust 2024-25 Overview of the...

MSOP1004 Infections-Central Nervous System Infections - Pyrexia of Unknown Origin Dr Veronica Chorro-Mari Consultant Pharmacist East Kent University Hospitals NHS Foundation Trust 2024-25 Overview of the session CNS infections Epidemiology and pathophysiology of meningitis Meningitis treatment PUO and handling Clinical scenarios  Objectives for CNS session To know the pathophysiology of Meningitis To understand and describe the signs & symptoms, causative pathogens and treatment of meningitis To appreciate the complexities of the blood-brain barrier To understand the clinical concept of ‘PUO’ To know appropriate antibiotics for ‘PUO’ National Early Warning Score (NEWS) Calculator National Early Warning Score (NEWS) 2 Meningitis Anatomy MYELITIS – inflammation of the spinal chord Meninges MENINGITIS – inflammation of the meninges ENCEPHALITIS – inflammation of the brain  Section of the brain LEPTO- MENINGES MENINGITIS – inflammation of the meninges ENCEPHALITIS – inflammation of the brain Anatomy MSCL- reading Scientific Publishing Understanding Meningitis Chart Laminated or Paper (universalmedicalinc.com) Meningitis- causes Causes Meningococcal disease (septacaemia) - is infection caused by Neisseria meningitidis Bacterial Meningitis- infection caused by other bacteria i.e, streptococcus pneumoniae, Haemophilus influenzae Viral meningitis Fungal meningitis (rare) Parasitic (rare) Non-Infectious (caused by cancers, tumours, head injury/surgery) Causes Inflammation of the leptomeninges (arachnoid mater and pia mater) Aseptic/non-bacterial causes: Viral e.g. mumps, HSV, enterovirus (coxsackie) Fungal e.g. cryptococcus Spirochaetal e.g. Treponemes these show a low WCC < 10 ml-1 Bacterial causes: Acute (pyogenic) - see below Chronic e.g. TB these show a high WCC Natural barriers to infection Blood-brain barrier – tightly joined endothelial cells surrounded by glial processes Blood-CSF barrier at choroid plexus – endothelium with fenestrations & tightly joined choroid plexus epithelial cells Meningeal Barrier: The meninges, the protective membranes surrounding the brain and spinal cord, serve as an additional physical barrier against pathogens. They are composed of three layers: the dura mater, arachnoid mater, and pia mater. Cerebrospinal Fluid (CSF) Flow: The continuous flow of CSF within the subarachnoid space provides mechanical clearance of pathogens and toxins, aiding in the removal of infectious agents that may breach the barriers. How do microbes get through? Growing across infecting the cells that comprise the barrier Passively transported across in intracellular vacuoles Carried across by infected white blood cells Microbes can also invade the peripheral nervous system e.g. herpes simplex, varicella-zoster & rabies viruses Invasive procedures Routes of bacterial infection Direct spread- Pathogen gains access inside skull or spinal column, penetrates meninges----> CSF Through skin, up through nose, anatomical defect (congenital—spina bifida) or skull fracture Haematogenous spread- spreads via BBB through binding to surface receptors, areas of damage, vulnerable area ie choroid plexus Body’s response to infection CSF cell counts increase ‘aseptic meningitis’ - lymphocytes particularly T cells & monocytes, slight in protein but CSF clear ‘septic meningitis’ -  polymorphonuclear leukocytes & proteins CSF becomes turbid  Meningitis signs and symptoms Signs & symptoms: stiff neck, rigidity, photophobia, rash: non-blanching, pyrexial Signs and symptoms Clinical: lumbar puncture for CSF (care not to damage / touch ‘floating’ nerves when accessing sub-arachnoid space) CSF: look for turbidity (should be clear and ‘sparkling’), measure protein, glucose, Cl-, globulin, WCC ↑ protein ↑neutrophils ↓glucose Spin CSF → chemistry; deposit → culture + slide (Gram + Leishman staining) Acute Bacterial Meningitis  Acute bacterial meningitis Main Causative organisms: Infants < 3 months old ----Group B Streptococcus, E.coli, Listeria Monocytogenes Infants >3 months and young children: Haemophilus influenzae type b, if younger than 4 years and unvaccinated; Neisseria meningitidis, Streptococcus pneumoniae. Adults and older children: S. pneumoniae, H. influenzae type b, N. meningitidis, Gram-negative bacilli (eg non-typeb H influenza, Klebsiella, Pseudomonas, Enterobacter), staphylococci, enterococcus species, streptococci and L. monocytogenes. Elderly and immunocompromised (+pregnant) : S. pneumoniae, L. monocytogenes, tuberculosis (TB), Gram-negative organisms Neisseria meningitis (1/2) Meningococcal meningitis – Neisseria meningitidis Usually commensal Prevalence increases through childhood from around 5% in infants to a peak of 24% in 19 year olds, decreasing in adulthood to around 8%. The mean duration of carriage in settings where prevalence is stable is around 21 months. The incubation period is usually 3–5 days. The onset of disease can vary from fulminant with acute and overwhelming symptoms to insidious with mild prodromal symptoms. N. meningitidis capsular group B (MenB) is the most common cause of meningococcal disease in people aged under 25 years. In 2015, a four-component MenB vaccine was included in the routine UK immunization schedule- see the CKS topic on Immunizations - childhood. Neisseria meningitis (2/2) 90% of bacterial cases intracellular, G-ve DC on slide prep. source: naso-pharynx (human only) – carriers may be epidemic organisms invade bloodstream → bacteraemia → meninges → meningitis (Rarely → other sites and becomes chronic) → septicaemia, which is fulminant within 6 hours (affecting adrenal glands causing haemorrhage and patient collapses rapidly) clinical picture: blood culture, (urgent) CSF in UK serogroups B & C are most common treatment (acute case)- third-generation cephalosporins In carriers: ciprofloxacin Streptococcus pneumoniae (1/2) Streptococcal meningitis – Strep. pneumoniae (alpha-haemolytic) some serotypes of pneumococcus may be carried in the nasopharynx without symptoms, with disease occurring in a small proportion of infected people. The incubation period is usually 1–3 days. Invasive pneumococcal disease (IPD) including meningitis, septicaemia, and pneumonia, is a major cause of morbidity and mortality, particularly in young children, immunocompromised and elderly. Pneumococcal vaccination is offered to all adults aged over 65 years and to all children (as part of the routine UK childhood immunization programme), as well as to other high-risk groups. Although over 90 different capsular types have been characterized, around 69% of invasive infections are caused by the 10 most prevalent subtypes. Streptococcus pneumoniae (2/2) Streptococcal meningitis – Strep. pneumoniae (alpha-haemolytic) most common at age extremes where it can easily be fatal (for elderly and neonates) treatment – cefotaxime or ceftriaxone Streptococcus pneumoniae colonisation: the key to pneumococcal disease - The Lancet Infectious Diseases Haemophilus influenza Haemophilus influenzae type b is an encapsulated, immotile and non-spore forming Gram- negative coccobacillus. H. influenzae is divided into capsulated and non-capsulated strains. Non-capsulated strains are sometimes referred to as “non-typeable”. Encapsulated strains express six antigenically distinct capsular polysaccharides which are classified as serotype a through f. Serotype b (Hib) has a polyribosyl ribitol phosphate (PRP) polysaccharide capsule that is a major virulence factor. The PRP capsule protects the organism from phagocytosis in the absence of anticapsular antibodies and facilitates penetration to the blood stream and the cerebrospinal fluid. Humans are the only known reservoir for Hib. Haemophilus influenza common in young children treatment – cefotaxime or ceftriaxone 10 days vaccine available – HiB – given alongside C for babies and in the teen combination (ACWY) Other spp Enterobacteriaceae – Escherichia coli Listeria monocytogenes treatment- third generation cephalosporins (previously with amoxicillin) Antibiotic treatment must get through BBB to CSF to work if meninges are damaged (as in meningitis), any antibiotic will pass and act, but as healing occurs so antibiotics will pass with increasing difficulty Therefore, high doses of antibiotics/ keep high, even as patient recovers In adults initially -Ceftriaxone OR Cefotaxime 2g IV immediately Penicillin/Cephalosporin anaphylaxis - Chloramphenicol 25mg/kg IV Chronic meningitis Tuberculous meningitis – Mycobacterium tuberculosis all cases ultimately haematogenous (seeded from earlier disease) Tuberculoma may form below meninges – a fibrous reaction to infection. Growth of tuberculoma applies pressure to meninges → chronic, but fatal, disease damage to brain occurs, so total recovery rare treatment: rifampicin / rifamycins Cryptococcal – Cryptococcus neoformans opportunistic infection in immunosuppressed treatment -antifungals diagnosed via India ink stain of CSF (shows capsule) Early warning signs EWS - crucial Early recognition is crucial Consider meningitis or meningococcal sepsis if ANY of the following are present: Headache Fever Altered Consciousness Neck Stiffness Rash Seizures Shock NICE Pyrexia of Unknown Origin (PUO) PUO clinical concept- Fever persisting for at least three weeks without an identified source despite extensive investigation acute (rarely chronic) differential diagnosis: age- neonates - sepsis, gp. B streps., enterobacteriaceae (esp. E. coli), Listeria spp.; elderly - due to malignancy travel- typhoid, malaria, ricketsias, Dengue fever, Tb, Legionnaires’ occupation / hobbies: water worker (? leptospirosis), farmer / vet (? brucellosis), lab. worker, caver (cryptococossis) contacts / pets: cats (? toxoplasmosis), birds (? psitticossis) PUO 2/2 infection most common cause infections caused by specific pathogen e.g. TB, Typhoid fever, campylobacter infections caused by a variety of different pathogens e.g. UTI, biliary tract infections Investigation classic PUO Step 1 – careful history taking, physical examination & screening Step 2 - reviewing history, repeat physical examination, specific diagnostic tests & non invasive investigations Step 3 – invasive tests Step 4 – therapeutic trial PUO 3/3 FULL examination required, to look for: rash splenomegaly (? malaria, typhoid) Lymphadenopathy pyrexia Focal point WCC: ↑ → ? pyogenic infection; ↓ → ? typhoid, virus microbiology: blood culture, serum serology: bone marrow / biopsy therapeutic trial – diagnose on response to treatment immunosuppression? cryptic abscess – do CAT scan Classic PUO vs specific patient groups Time frame Classic – weeks to months Specific – hours to days Types of specific: Nosocomial (hospital acquired) Neutropenic HIV-associated Pharmacist role START SMART then FOCUS Stop antibiotics if there is no evidence of infection Switch antibiotics from intravenous to oral Change antibiotics – ideally to a narrower spectrum – or broader if required Continue and review again at 72 hours Outpatient Parenteral Antibiotic Therapy (OPAT). Summary, you should be able to now know: Know the pathophysiological differences between meningitis and encephalitis Understand and describe the signs & symptoms, causative pathogens and treatment of meningitis Know the difference between bacterial and ‘aseptic’ meningitis Appreciate the complexities of the blood-brain barrier and how that influences treatment regimens Know appropriate antibiotics for named CNSIs Understand the clinical concept of ‘PUO’ and the importance of clinical history in its diagnosis Superbugs and Hospital Acquired Infections (HAI)→ for year 4 AMS next 2024-25 Objectives Know the pathophysiological differences between various resistant strains of bacteria (superbugs) Understand and describe the signs & symptoms, causative pathogens and treatment of resistant strains Know appropriate infection precautions and antibiotics to treat infections caused by resistant bacterial strains What are superbugs? strains of bacteria that are resistant to several types of antibiotics Types of Superbugs Methicillin-resistant Staphylococcus aureus (MRSA) Carbapenem resistant Enterobacteriaceae (CRE) ESBL-producing Enterobacteriaceae (extended-spectrum β- lactamases) Vancomycin-resistant Enterococcus (VRE) Multidrug-resistant Pseudomonas aeruginosa Multidrug-resistant Acinetobacter E.coli H30-Rx: The H30-Rx strain of antibiotic-resistant E. coli bacteria has become a main cause of bacterial infections in women and the elderly worldwide over the past decade. MRSA Major concern in UK Staphylococcus aureus common bacteria found on skin, in nostrils & throat Known to cause boils & impetigo Can cause septicaemia & endocarditis if breach skin barrier  Spread of MRSA Considered (with c.diff) to be a Healthcare associated infection (HCAI) Healthcare-associated infections (HCAIs) can develop either as a direct result of healthcare interventions such as medical or surgical treatment, or from being in contact with a healthcare setting) Huge expense to NHS (money, lost bed days, ↑ staff burden) skin to skin contact contact with contaminated objects such towels, sheets, clothes, dressings, surfaces, door handles and floors  Spread of MRSA higher risk when in hospital lots of people – more organisms available (opportunistic organisms i.e Pseudomonas aeruginosa (cystic patients), MRSA, C.diff, CRE, VRE) may be an open wound- surgical patients illness increases vulnerability- i.e patients with compromised immunity, pre- existing co-morbidities (copd, cancer, diabetes), elderly + frail Relatives/ visitors (noro and rota virus) Increased use of antimicrobials- leading cause of Clostridium difficile and some antibiotics increase risk of MRSA. (Both very contagious)  Prevention Hand washing Alcohol gel Isolate patient (single room occupancy) Screening e.g. pre-operatively ➔ eradication regimens: chlorhexidine 4% wash or Octenisan® + mupirocin 2% nasal ointment (5 days—2 courses only) Meticulous aseptic technique + meticulous cleaning Targets set for achieving low (or zero) rates of MRSA bacteraemia by CCGs for Trusts Infection prevention and control is a key priority for the NHS. Treatment Beta-lactam antibiotics ALL RESISTANT Glycopeptides- (vancomycin, teicoplanin) Sodium Fusidate Trimethoprim Often need dual AB’s depending on infection as may not be MRSA alone Resistance increasing Role of pharmacist Infection prevention control is paramount to prevent HCAI’s and superbugs ‘Start SMART then FOCUS’ Right Drug, Right Dose, Right Time, Right Duration –Every time. R/V all antibiotics 48 hr- 72 hours and leave/ amend as appropriate Wash hands, use alchohol gel, good hand hygiene Monitor prescribing Clostridioides difficile C. difficile C. difficile bacteria are found in the digestive system of about 1 in every 30 healthy adults. Harmless when living with other gut bacteria Antibiotics can affect natural gut flora Overgrowth of C.diff & toxin production ➔ illness Spores shed – highly resistant Associated as being a HCAI Reportable to UK Health Security Agency Diagnosis TWO test protocol Glutamate Dehydrogenase screen (GDH) or NAAT + sensitive toxin EIA test (toxin immunoassay)  DIAGNOSIS If GDH EIA (or NAAT) +ve and toxin EIA +ve = C. difficile (infection) most likely to be present and a case associated with poor outcome. Result must be included in mandatory reporting; If GDH EIA (or NAAT) +ve and toxin EIA -ve = C. difficile present but possibly NOT infective i.e. potential C. difficile excretors – do not include in mandatory reporting; If GDH EIA -ve and toxin EIA -ve = C.difficile not present or CDI is very unlikely to be present – do not include in mandatory reporting. Prevention of spread Spores found on hands, surfaces, objects & clothing Survive long periods Thorough cleaning for eradication Keep patient isolated (single room occupancy) Alcohol gel DOES NOT WORK ➔ WASH HANDS!!! Treatment- updated guidance 2021 1st line- vancomycin PO 125mg QDS 10 days OR 2nd line –Fidaxomicin PO 200mg BD 10 days  ABUSE THEM AND WE’LL LOSE THEM  Case Study 1: Methicillin-Resistant Staphylococcus aureus (MRSA) Infection 55years old male post orthopaedic surgery Surgical ward in acute hospital. Developed a surgical site infection due to MRSA (strain of Staphylococcus aureus resistant to methicillin and other beta-lactam antibiotics). Case Study 1: MRSA Challenges Initial antibiotic treatment with beta-lactams failed. MRSA required alternative antibiotics, like vancomycin. Prolonged hospitalisation and increased healthcare costs. Risk of systemic spread and severe complications. Case Study 2: Escherichia coli A 65-year-old female patient with a urinary tract infection. Lives in a long-term care facility UTI persisted despite initial antibiotic therapy. ESBL-producing Escherichia coli, resistant to most beta-lactam antibiotics. Case Study 2: Escherichia coli Challenges Extended-Spectrum Beta-Lactamase (ESBL) production detected, limiting treatment options. Increased risk of bloodstream infection due to UTI. Requirement for complex antibiotic combinations. Potential for transmission to other residents.  Case Study 1 and 2 Lessons learned Strict infection control and surveillance are crucial in long-term care settings to prevent MRSA transmission and other HAIs Appropriate samples taken at the right time Time identification vital Appropriate diagnostic testing is essential for detecting resistance early and guiding effective treatment.