Acute Infection Flashcards

Question

Is there a role for post-exposure prophylaxis?

Answer 1

* only recommened for meningococcal infection * aim - to eradicate nasal carriage of N. meningitidis * offered to: * close contacts - living in same house or sharing kitchen in halls of residence * high risk exposure - exposed to airway secretions e.g. intubation or CPR (thereofre some staff may need treatment) * recommmended treatment * ciprofloxacin oral for a single dose * rifampicin oral for 2 days * ceftriaxone IM inhection for a single dose

Answer 2

* UK infants are routinely vaccinated against: * haem influenzae B - previously one of the leading causes * meningitis ACWY * meningitis B * strep pneumoniae

Answer 3

* viruses are the most common cause of meningitis in the UK * **_enteroviruses_** \> HSV 1&2 \> VZV * enteroviruses - think of this particularly if viral meningitis develops after vomiting bug * difficult to reliably differentiate from bacterial meningitis on the basis of clinical assessment * LP is diagnostic * lymphocytosis with relatively normal protein and glucose * virus detection by PCR on cerebrospinal fluid * self-limiting and managed supportively * no evidence for benefit of anti-viral treatments * causes significant long-term morbidity * particularly fatigue, headaches, slowed thinking and mood disturbance * effects can last for many months

Answer 4

* common * back pain, shooting pain down legs at time of procedure (occurs if off centre and patients need to notify you if they are experiencing any of these symptoms), localised bleeding * rare (\<1%) * persistent headache (due to persistent leak of CSF), infection, lower limb weakness

Answer 5

* Explain the procedure * A ‘spinal tap’ that involves using a needle to obtain a sample of the fluid surrounding the brain and spinal cord from a space between vertebrae in the lower back * Describe the likely benefits * To aid diagnosis (therapeutic if raised intracranial pressure) * List common and important risks

Answer 6

* diagnostic * infection - meningitis (bacterial/viral/fungal) or encephalitis * sub arach * other - MS, malignancy * therapeutic * reduce ICP e.g. idiopathic intracranial hypertension * spinal epidural * pain relief (during labour) * anaesthesia (e.g. lower limb surgery)

Answer 7

* **Indications for brain imaging prior to lumbar puncture** * **This is due to the risk of brain herniation through the foramen magnum** * Focal neurological signs * Presence of papilloedema * Continuous or uncontrolled seizures * Reduced or fluctuating conscious level * **Bleeding risk** * Deranged blood clotting or a low platelet count * Taking anticoagulation ( e.g. warfarin if INR \>1.4) * **Others** * Signs of severe sepsis or a rapidly evolving rash (indicating risk of coagulation problem) * Infection at the site of the lumbar puncture

Answer 8

* US guided technique should be used * Positioning allows for the largest possible gap between vertebrae * Lying on the side can be difficult to find landmarks so a sitting position can be used, however you cannot measure opening pressure in sitting position as this would be increased by gravity * Needle introduced in the L3/4 space, however L2/3 and L4/5 can be used depending on the anatomy of the patient

Answer 9

**Appearance** * Normal - clear (‘gin-coloured’) * Cloudy/purulent – meningitis * Blood-stained - subarachnoid haemorrhage, or a traumatic tap **Opening pressure** * Normal is 8-20cm * May be elevated due to infection, inflammation, haemorrhage and idiopathic intracranial hypertension

Answer 10

**Cell count** * Red blood cells * Normal – 0-10 cells/ul * ↑ traumatic tap, subarachnoid haemorrhage * White blood cells * Normal – 0-5 cells/ul * ↑ neutrophils – bacterial meningitis * ↑ lymphocytes – viral & TB meningitis/ encephalitis, (& inflammatory conditions, malignancy) * In real life it is often not as clear cut and may be a mixed picture * **Protein** * Normal - 0.15-0.45 g/L * ↑infection (TB \> bacterial \> viral), inflammatory conditions, Guillain-Barre syndrome * Oligoclonal bands in multiple sclerosis * **Glucose** * Paired with blood glucose * Normal - 60-80% of serum glucose * ↓ (\<50%) in infection (esp. bacterial, TB and fungal)

Answer 11

**Gram positive** * Peptidoglycan wall retains crystal violet stain (dark purple) * pneumococcal meningitis * Streptococcus pneumoniae is a gram-positive, α-hemolytic, lancet-shaped diplococcus - catalase-negative but produces hydrogen peroxide. **Gram negative** * Crystal violet not retained by cell wall; counter stained with safranin stain (pink) * Meningococcal meningitis * gram negative coffee-bean shaped diplococci

Answer 12

* Gram positive bacteria take up the basic dye (crystal violet) * Their **thick peptidoglycan** cell wall allows them to resist alcohol decolourisation and they retain the dark purple colour * Gram negative bacteria allow the crystal violet to wash out and so decolourise * Their thin cell wall is less stable * The decolourisation bacteria can then be counterstained pink with further application of a different dye, safranin

Answer 13

Gram positive cocci Round or oval shaped Sometimes you can guess what they might be by their shape and chain formation (but you can’t confirm unless you have colonies on a culture to test) eg: 1. Strep pneumoniae – tends to form typically lancet shape and like to group in pairs 2. Enterococci (a subset of Streptococci) – tend to form short chains 3. Oral (viridans) Streptococci (inhabit oral mucosa) – can form long chains 4. Strep pyogenes – medium to long chain

Answer 14

* grown on agar containing 5% sheep blood incubated in 5-10% CO2 * greyish white colonies * may be shiny or matte depending on type

Answer 15

**Catalyse test:** * scoop a colony on a small loop and dip into hydrogen peroxide solution * staphs contain catalase: H2O2 --\> H2O + O2 and bubbles indicate a positive test * streps are catalyse negative (no bubbles)

Answer 16

Streptococci produce extracellular enzymes that lyse the red blood cells in the agar. This can result in complete or partial clearing seen around colonies. The type of haemolysis present helps differentiate between possible species of streptococcus and can guide further identification steps.

Answer 17

Sometimes specific species do not need to be known as they will not affect management, however there are certaiin circumstances where it does need to be known: * in infections such as endocarditis, we need to know the species eg Streptococcus gallolyticus and specific antibiotic susceptibility profile in order to give optimal, evidence based, tailored treatment Further tests include: * mass spectrometry * panel of biochemical reactions

Answer 18

_Standard method in the lab:_ * Discs of filter paper impregnated with specific concentrations of antibiotics placed on agar plate which has been evenly spread with the bacteria and diluted in water * Antibiotic concentrates in agar around disc * Zones of inhibition of bacterial growth around discs suggests the particular antibiotic kills the bacteria * The bacteria is reported as susceptible to the antibiotic _E tests_ * MIC = minimum inhibitory concentration. More specific than disc testing * MICs may be useful in deciding which antibiotic to use for planning long courses for deep infections

Answer 19

* Sustained or recurrent pyrexias for ≥3 weeks * No identified cause after sufficient evaluation: * in hospital for 3 days * ≥3 outpatient visits * No diagnosis

Answer 20

* 'Classic' * nosocomial * immunodeficient * HIV

Answer 21

**Infection** * Abscess * Infective endocarditis * Tuberculosis * Complicated UTI * Geography/travel * Melioidosis * Visceral leishmaniasis * Amoebic abscess **Connective tissue** * Young * Still’s/JRA * Adult * Rheumatoid arthritis * SLE * Elderly * giant cell arteritis * polymyalgia rheumatica As population age increases, cancer is more likely as cause of PUO.

Answer 22

* hospitalised for \>48 hours * no infection present or incubating at admission * diagnosis uncertain after \>3days of appropriate evaluation * (microbiology cultures incubated for \>2 days)

Answer 23

* catheters/devices * thrombophlebitis * UTI/RTI * drug fevers * C. diff * ICU - ventilator, ET tubes, NG tubes * stroke

Answer 24

* Cell-mediated immunodeficiency * Congenital * Biologic/immunomodulatory therapies * Neutropenia * Haematological disorders * Chemotherapy * \<500 neutrophils/ul * N.B blunted ‘typical’ inflammatory responses * N.B lack of radiological changes

Answer 25

* primary HIV infection 'seroconversion illness' --\> AIDS * PCP * mycobacterial * toxoplasmosis * CMV * lymphoma

Answer 26

**Laboratory** * Blood cultures * Blood-borne viruses (BBV) – HIV/HBV.HCV * Blood films – cells, parasites * Serology * FBC – differential * U+E/LFT/bone chemistry * TFTs * Inflammatory markers – CRP, ESR, ALP * Auto-antibodies – ANA, dsDNA * Stool, urine, sputum, swabs * Ascitic/pleural/synovial fluid * Bone marrow * Biopsy **Imaging** * CXR * US – liver/spleen * Cross-sectional CT * HRCT * CT PET * Labelled white cell scan (scintigraphy) * Bone scan * MRI

Answer 27

* Symptoms/signs * Fever: important to define pattern * Rash * Arthralgia * GI symptoms * Abdo pain, diarrhoea, constipation, blood * Full systems review * Including neuro and GU * Investigations * Full blood count * U&Es * LFTs * Coagulation * Blood gas * Blood culture * Throat/sputum/stool/urine/CSF as appropriate * Special tests * Malaria films * Serology * E.g Rickettsiae, Dengue, HIV, Viral hepatitis, Syphillis * PCR * E.e Dengue (blood), Herpes + enteroviruses (CSF), TB * Special stains – ZN/auramine (TB), Grockott (fungi) * Special cultures – mycobacterial, fungal

Answer 28

South East Asia and South America

Answer 29

* aedes aegyptii and aedes albopictus

Answer 30

* Incubation period is 4~21 days * Sudden onset with a fever * 1st week, systemic toxic symptoms * 2nd week, get worse, complication * 3th week, convalesce (if prompt diagnosis and treatment)

Answer 31

* fever * normally normal WCC * fairly normal PLTs * HCT may be normal

Answer 32

* normally after about day 4 * Manifests with shock and bleeding as capillaries tend to start to leak, therefore plasma starts to leak out into extravascular compartment * As a result, there is marked drop in the WCC and PLTs, as a result HCT increases * Intravascular compartment becomes depleted * Need to recognise this because it is key to management of patient, and also important as when the patient begins to recover, they begin to reabsorb the fluid and so you must be careful not to fluid overload them at this point.

Answer 33

During the febrile phase, there is high viral load and so PCR can be used to detect the virus (dengue antigen capture ELISA can be used to rapidly diagnose within 30 minutes). However, at the end of the febrile phase IgM/IgG antibodies start to climb and so these are used for diagnosis during the critical and recovery phase.

Answer 34

**5 days or less post onset of fever:** * Detection of viral RNA (RT-PCR) * Detection of viral antigen (NS1) **5 days of more post onset of fever:** * Detection of IgM antibodies host response as host response to infection (IgM antibodies can last up to 6 months; a positive IgM test is only suggestive of recent infection) * Detection of IgG antibodies (IgG antibodies persist for life; a positive IgG test result proves evidence of post infection) **Use of RT-PCR + IgM or NS1 + IgM tests can extend the window of detection of acute dengue to 10 days post onset of fever.**

Answer 35

* treatment is mainly supportive * in the febrile phase * prevent dehydration * in the critical phase * correct dehydration * replace ongoing losses * in the recovery phase * prevent fluid overload

Answer 36

Tsutsugamushi triangle * North - northern Japan and far-eastern Russia * South - northern australia * West - to pakistan and afghanistan

Answer 37

**Eschar** * Probability: higher than 60% * Location: axillary fossa, inguinal region, perianal region, scrotum, buttocks and the thigh * Appearance: an ulcer surrounded by a red areola, is often covered by a dark scab * This is the most specific manifestation of scrub typhus **Maculopapuplar rash** * Onset: appear at the end of the 1^st week, lasts 3~7d * Location: chest, abdomen, whole trunk, or upper and lower limbs. Rarely involves the face, palms and soles **Lymphadenopathy** * Regional lymphadenopathy: * Occur at the end of the 1^st week * Localise: the draining lymph node around the primary eschar * Characterised by tenderness and enlargement * Generalised lymphadenopathy: appears 2-3 days later

Answer 38

* Haematology: * Leukopenia * Normal total WBC * May be elevation if patient has presented with some complications * Biochemical: * Injury of liver function, CRP **Serological examinations** * Weil-felix: can be positive as early as 4^th day after onset – used in poorer healthcare infrastructures * \>1:160 or increase 4 times during the course * Easy for operation (easily accessibility) but poor for specialisation (poor specification and sensitivity) * Gold standard for diagnosis: indirect fluorescent antibody) * positive at end of first week * IIP (indirect immunoperoxidase test): comparable to those from IFA. More available **Pathology** * Early course: perivascular lymphohistiocytic and extravasated erythrocytes and dermal oedema * Advanced lesion – shows dermal and epidermal necrosis * Immunohistochemical – positive staining for R. rickettsie

Answer 39

* Epidemiology data: visit the endemic area during the past 3 weeks. Working, camping or sitting on grass * Clinical manifestation: Eschar, regional lymphadenopathy, fever, maculopapular rask, leukopenia, failed therapy with common antibiotic drug * Laboratory examination: Weil-felix reaction with titers beyond 1:160 or fourfold rise during the course of the disease * (PCR for Orientia tsutsugamushi from blood of feverish patient)

Answer 40

* **Epidemic typhus**: occurs in winter and spring, bite by louse, Weil-felix with OX19 is positive * **Typhus**: slow onset, persistent high fever, confusion, bradycardia, digestive symptoms, rose rash, no eschar, widal test positive. Blood culture to typhus bacillus is positive * **Leptospirosis**: tenderness of calf muscle, microscopic haematuria

Answer 41

* Sensitive antibiotics decrease fatality from as high as 30% (untreated) to 2% * **General treatment** * Supportive IV fluids * Intensive nursing care and prevent complication * **Pathogen treatment** * Chloramphenicol: 2g per day for adult, 25mg/kg of bw per day for children * Doxycycline: 0.2g per day for adult (tetracycline alternative) * Azithromycin 500mg daily * Roxithromycin: 0.6g per day for adult, 2~3mg/kg/d for child * Strains resistant to doxycycline and chloramphenicol * Combination therapy with doxycycline and rifampicin should be used if resistance suspected * Azithromycin – shown to be promising against strains that are resistant from

Answer 42

* _**Plasmodium falciparum** (Malignant tertian)_ * **Plasmodium vivax (**Benign tertian) * **Plasmodium ovale (** “ “ ) * Vivax and ovale are also important to know about as they cause debilitating disease however they are rarely fatal * These species are known to have a dormant liver stage which can lead to relapsing episodes of clinical malaria * **Plasmodium malariae (**Quartan) * Can cause low levels of disease with periods of recrudescence that may go on for many years or even decades but it is currently less important than it has been in the past in terms of global burden of incidence * **(plasmodium knowlesii** infrequent. Probably zoonosis) * Infrequently diagnosed in humans, probably zoonosis that effects monkeys much more

Answer 43

* When the erythrocytic stage is initiated, a periodicity sets in and cycles of red cell ruptures starts happening roughly every 48 hours (**this is what earns the tertian periodicity fever which is classical of falciparum malaria – fever spikes every 48 hours**)

Answer 44

* **Sequestration:** Falciparum malaria itself gives rise to malignant disease itself – the shape of the red cell becomes distorted and the surface of the red cell becomes covered in little lumps (which are clumps of parasitic protein which are electrically charged). * Altered rheology – alters flexibility of red cells * Electrical charge * Intra-cellular adhesion (likely to adhere to each other, to other cells and the intima of vasculature) (Again, this mainly happens in falciparum malaria). Red cells therefore become sequestrated in microvasculature, some tissues being more susceptible than others (brain, kidneys, eventually tissues such as bowel mesentery, pulmonary bed and digital extremities). Clinically can cause: * **Cerebral malaria** – reduced GCS and seizures * **Renal failure** – either biochemical changes or oliguria leading to anuria * **ARDS** - people with falciparum are particularly susceptible to pulmonary oedema and an ARDS picture * **Tissue acidosis** – direct result of sequestration as this can cause an infarct in capillary beds leading to tissue hypoxia and acidosis * **Coagulopathy** – accumulating tissue damage exacerbates any coagulopathy present

Answer 45

Vivax and ovale species will not only produce merozoites in schizonts in the liver, but also hypnozoites which remain dormant in the liver – this allows the parasite to survive in the human host during cooler parts of the year in more temperate environments and will re-emerge when the mosquito vectors are feeding more actively

Answer 46

Jaundice and haemolytic anaemia can occur when large numbers of red cells are infected and then all rupture.

Answer 47

When trophozoites are readily feeding on glucose in the blood, this will cause levels to decrease in the blood. This is also partly explained by increased basal metabolic rate in infected cells.

Answer 48

Anyone returning from a malaria endemic area with: * Fever (or a history of fever) Other features (not always present): * Rigors * Headache +/- confusion * Myalgia, arthralgia * Nausea, vomiting, diarrhoea * Dark urine **Fever + travel history = think of malaria and do a blood film!!**

Answer 49

* Fever * Jaundice * Pallor * Splenomegaly * Hepatomegaly * Altered consciousness * Focal neurological signs * Coma

Answer 50

* Cerebral involvement – reduced GCS/seizures * Anaemia – Hb \< 8g/dL * Lactic acidosis – pH\<7.3 (i.e. need to do ABG or VBG to monitor lactate) * Renal failure * Oliguria \< 0.4ml/kg/hr * Creatinine \> 265 * Pulmonary oedema/ARDS * Hypoglycaemia – BM \<2.2mmol/L * Shock – BP \<90/60 * Bleeding/DIC * Haemoglobinuria

Answer 51

* characteristic double chromatin dots * usually only one in each cell * a cell is said to be hyper-parasitised when there are two trophozoites in the same cell

Answer 52

* contains many merozoites * if we see schizonts on the film, then we know the current parasitaemia may increase by 10-fold in the near future when it ruptures

Answer 53

**Uncomplicated: ALL of the following** – these patients would be suitable for oral treatment if there were no further issues, as long as they are not vomiting are able to take oral medications * Parasitaemia \<2% * No schizonts * No clinical complications **Potentially severe: ANY of the following** – IV treatment * Parasitaemia \>2% * Parasitaemia \<2% with schizonts * Parasitaemia \<2% with complications **Severe** – IV treatment * Complications present, *regardless of parasitaemia*

Answer 54

* P. vivax: Asia, South America * P. ovale: West & Central Africa * Both vivax and ovale are usually associated with **lower rates of parasitaemia (\<2%)** and due to not causing sequestration of RBCs we don’t see cerebral malaria, renal failures and capillary bed ischaemia with these species * Hypnozoites (get in both vivax and ovale) – if these are not eradicated along with the active infection then you will get relapse in the future * Dormant liver stage * Relapsing malaria * P. malariae: * Least common * Never causes severe disease * May persist for decades * Rare cause pf nephrotic syndrome

Answer 55

**Quinine** * Cardiac toxicity (due to sodium channel blockade) – ECG monitoring required (prolonged QT intervals and wide QRS complexes) * Cinchonism – tinnitus vertigo, vomiting, headache, nausea, abdominal pains and occasionally visual disturbance (sometimes temporary blindness) * Rarely an indication to stop treatment * When patient is ready to switch to oral treatment, continuation with oral therapy must be with a second agent (doxycycline or clindamycin) **Artesunate** * Standard of care globally is currently IV artesunate as first-line for severe malaria, however not currently licenced in the UK so sometimes there is a problem with supply – this is improving * Minimum 24 hours therapy, however if after this the patient is improving then a switch can be made to oral treatment * Delayed post-treatment haemolysis at about 70 days so patients need to be warned about this

Answer 56

* Artemether-lumefantrine: 4 tablets then 4 tablets at 8, 24, 36, 58 and 60h * First-line in the UK * Atovaquone/proguanil (Malarone): 4 ‘standard’ tablets daily for 3 days * Quinine sulfate 600mg 8 hourly for 5-7 days plus doxycycline 200mg daily (clindamycin 450mg 8 hourly for pregnant women) for 7 days

Answer 57

* Primaquine 2 weeks, oral * G6PD enzyme activity must be measured before taking this drug * G6PD deficiency – at risk of haemolysis due to oxidative stress imposed by metabolising this drug * These patients may need to be treated at a lower dose for a longer time, but expert advice should always be sought

Answer 58

**Causal** * Directed against hepatic stage (i.e. schizonts, not hypnozoites) * Prevents progression to erythrocyte stage * Continue for 7 days following last possible exposure * **Examples: atovaquone/proguanil (malarone)** **Suppressive** * Directed against erythrocytic stages * Continue for 4 weeks post-exposure * **Examples – chloroquine** (rarely used for falciparum prophylaxis these days due to widespread resistance), **doxycycline** (very fair-skinned individuals need to be warned about hypersensitivity to sun and frequently causes GI upset), **mefloquine** (once weekly – should not be to patients with strong history of severe depression or psychological history due to side effects)

Answer 59

* P. falciparum: Widespread, but primarily in tropics and subtropics * P. vivax: Widespread in tropical and subtropical areas and extends into temperate areas. Relatively uncommon in Africa * P Malariae: Broad but patchy geographical distribution * P. ovale: Primarily tropical Africa and west pacific islands. Sporadic distribution in SE Asia. NOT found in S America or Indian subcontinent but, there have been a small number of cases reported in Bangladesh. * P knowlesi: Confined to SE Asia

Answer 60

* FBC * Thick and thin films * Carestart Combo Rapid Test (pan pLDH/falcip HRP-2) **A negative malaria film does not exclude a diagnosis of malaria. If there is a strong suspicion of malaria but the initial films are negative, then repeat films should be requested 12-24hrs and 48hrs.**

Answer 61

* Particular note should be taken of the patient’s platelet and WBC counts * Malaria can often be associated with reduced leukocyte/neutrophil numbers * Platelet numbers are moderately or markedly reduced in approx. 80% of patients with malaria * Malaria parasites DNA/RNA can show as fluorescent populations on haematology FBC analysers that utilise flow cytometry

Answer 62

* blood is centrifuged in a capillary tube coated with acridine orange * the parasites separate into their own level * the acridine orange stains nucleic acid which then fluoresces when excited with blue light when examined under a fluorescent microscope (i.e. you can see the malaria)

Answer 63

* The gold standard for malaria screening * Thin films are fixed in methanol and stained with a MGG stain pH 6.8 * Additional diagnostic information can be gained by examining Giemsa-stained thin films pH 7.2 * Thick films are stained unfixed with Fields stain pH 7.2 (screening)

Answer 64

* strip pre-coated with two different monoclonal antibodies * two different capture lines * one test line (i.e. monoclonal antibody) is specific to falciparum and one is specific to vivax, malariae and ovale * there are relatively high rates of false positive and false negatives therefore these tests should never be used in isolation and thick and thin films must be examined

Answer 65

* Parasite nucleic acids are detected using polymerase chain reaction (PCR). * Although this technique may be slightly more sensitive than smear microscopy, it is of limited utility for the diagnosis of acutely ill patients in the standard healthcare setting (slow) * PCR results are often not available quickly enough to be of value in establishing the diagnosis of malaria infection. * PCR is most useful for confirming the species of malarial parasite after the diagnosis has been established by either smear microscopy or RDT.

Answer 66

* Antibodies to malaria can be detected using enzymatic immunoassays or immunofluorescence techniques. * The antibodies to the asexual blood stages appear days to weeks after the infection and may persist for months. * Although useful in survey work or for screening blood donors and reducing wastage, they are of little value in the "acute" malaria situation.

Answer 67

* **Haematogenous spread** * Associated with staph aureus * Children are at risk of salmonella and so can get hematogenous infection of native bone by salmonella * TB can be spread hematogenously to bones * **Direct inoculation** * People who have had metal plates inserted are at risk of direct inoculation (coagulase negative staphylococci) * These often form biofilms of the surface of the metal – these types of infections are very difficult to eradicate with antibiotics alone * Contiguous spread * for example diabetic ulcers (or any type of ulcer) can cause polymicrobial infections of the bone (which can then spread via haematogenous route)

Answer 68

* a structured community of microorganisms adhering to a surface and producing an extracellular matrix of polysaccharides” * (i.e. another community of bacteria in a blob of extracellular matrix that adheres to a surface – behaves very differently than other bacteria floating free) * very associated with device related infections but you do not need prosthetic material in your body to have a biofilm * chronic osteomyelitis is often assciated with biofilms * sessile (refers to bacteria in biofilms) ve planktonic (free bacteria) * sessile bacteria are relatively resistant to immune defences and antibiotics

Answer 69

* Clinical presentation is highly variable * _Septic arthritis_ tends to present with rapid onset of pain, swelling and redness in a single joint * _Prosthetic joint infection_ may present with joint pain & evidence of inflammation at the surgical site * _Vertebral osteomyelitis_ presents with back pain & may progress to cause neurological signs * _Chronic osteomyelitis_ often causes **a sinus which does not heal** (sinus is a break in the skin that does not heal and often discharges bits of dead bone)

Answer 70

* Bedside tests * Fever is often absent * Blood tests * RBC, U&Es, CRP, blood cultures * Microbiology tests * Joint aspiration, bone biopsy, tissue biopsy, sonication of excised prosthetic material * Radiology * Plain X-rays, CT scans, MRI scans

Answer 71

* “Medical” v. “Surgical” management (debridement many be the most important component of treatment) * Antibiotic therapy needs to be directed at the organism isolated or empirical therapy is necessary (I think flucloxicillin can be used empirically - see BNF treatment summary) * Antibiotics which penetrate bone well are preferred * Courses of antibiotics need to be relatively prolonged * Four weeks for septic arthritis * At least 6 weeks for vertebral osteomyelitis & prosthetic joint infections * Prolonged courses of IV therapy may be delivered via ‘OPAT’ clinics * Oral therapy may be as effective as IV therapy in many cases

Answer 72

* Purulent monoarthritis and/or * Triad of tenosynovitis, dermatitis (papules, pustules, necrotic lesions) and asymmetric migratory polyarthralgia * May occur several days to weeks following initial infection

Answer 73

* Female sex * HIV infection * Menses * Low socioeconomic or educational status * Pregnancy * Multiple sexual partners * SLE * Complement deficiency

Answer 74

* Blood culture (may be negative) * Synovial fluid analysis (joint aspirate) * Gram stain will show **inflammatory effusion with neutrophil predominance plus or minus gram-negative diplococci** * neisseria gonorrheae is oxidase positive and catalase positive * Culture & sensitivity testing * NAAT PCR (if available and validated for synovial fluids)

Answer 75

* IV ceftriaxone 2 weeks with appropriate oral switch for further 4 weeks (e.g. oral cipro) * Joint drainage for purulent arthritis (may need to be repeated several times)

Answer 76

* symmetrical polyarthralgia * similar to rheumatoid * arthritis is transient * other symptoms of parvovirus include: * prodromal illness that consists of fever, malaise, headache, myalgia, nausea and rhinorrea * risk factors include exposure to children (i.e. teachers at risk)

Answer 77

Definition: the infection of 1 or more joints cause by pathogenic inoculation of microbes. **Presentation** * painful joint * hot joint * swollen joint * restricted joint

Answer 78

* clinical * joint aspiration for urgent gram stain, culture and sensitivity

Answer 79

* Empirical antibiotic therapy should be commenced once appropriate cultures have been taken * according to NICE: * flucloxicillin * if penicillin allergic * clindmycin * if MRSA suspected * vancomycin (or teicoplanin) * if gonococcal arthritis or Gram-negative infection suspected, cefotaxime (or ceftriaxone) * other management * Depending on result of Gram stain likely require joint washout / orthopaedic intervention for definitive treatment * Rationalise antibiotics according to positive cultures * If haematogenous spread, ensure full systemic enquiry and appropriate investigations to ensure no seeding elsewhere

Answer 80

Staphylococcus aureus highly pathogenic and very likely a causative organism for either post-operative wound infection or early prosthetic joint infection. Remember on gram stain: * appear as gram positive cocci in clusters

Answer 81

* if MRSA suspected cover with e.g. teicoplanin, vancomycin, linezolid * broad spec agent that covers gram negative bacteria - piperacillin/tazobactam (Tazocin)

Answer 82

The most likely diagnosis is early onset prosthetic joint infection secondary to Staphylococcus aureus: * Gram positive cocci in clusters, catalase positive, coagulase positive organism Antibiotics alone will not be able to treat this. Prompt surgical action must be taken to optimise the changes of salvaging the prosthesis.

Answer 83

* Health & Safety at Work Act 1974 * COSHH (Law on the Control of Substances Hazardous to Health) * Workplace Regulations * Building Regulations * HTM’s (health technical memoranda) & HBN’s (health building note) * Comprehensive advice and guidance on the design, installation and operation of specialised building and engineering technology used in the delivery of healthcare

Answer 84

* Team of specialities that creates, implements and maintains a Water Safety Plan (WSP) * WSP – designed to ensure that the water used in hospitals and similar healthcare settings is safe to use by patients, staff and visitors, and poses minimal risk of infection from waterborne pathogens

Answer 85

* Pseudomonas * Legionella Need to consider high risk groups: * immunocompromised * children * burns * ICU

Answer 86

* types of taps/sinks * areas with los use (not flushing pipes/taps) * redundant piping

Answer 87

**Ventilation is a means of remvoing and replacing the air in a space:** * dilution of contaminants * clean airflow path * control of hazards * comfort

Answer 88

* infected patient in isolation: * air from anteroom flows into patient's room

Answer 89

* when a patient needs protected from infection e.g. neutropenic * air flows from patient room into anteroom

Answer 90

* joint replacement/orthopaedic operations

Answer 91

**Airborne transmission** Spread of an infectious agent caused by the dissemination of droplet nuclei/aerosols (\<5u) that remain infectious when suspended in air over long distances and time (vs droplet transmission \>5-10u) * TB, measles and chickenpox * n.b. * viruses - 0.1u * M. TB - 2-4u * bacteria - 10-16u * fungi and spores - 3-10u * It is important to have appropriate ventilation to prevent airborne infection

Answer 92

* Surgical Operating departments * Aseptic Pharmacies (production) * UCV Theatres * Burns units * Laboratories * Obstetrics / Maternity departments * Isolation rooms / wards (both +ve & -ve) * Laser Surgical units * Imaging units (CT, MRI, X- Ray, etc.) * Pathology departments * Mortuaries * Steriliser / packaging units (CSSD’s) * Hydrotherapy units * Infectious diseases units * Intensive Treatment / Therapy units

Answer 93

* **M**ethicillin **R**esistant **S**taphylococcus **a**ureus * *Staph aureus* is a Gram-positive bacterium that causes infections such as cellulitis, pneumonia, endocarditis and device-related infections * It can also colonise the skin and nasopharynx of healthy people without causing infection * _MRSA is resistant to methicillin – and hence also flucloxacillin_ * It is often resistant to other antibiotics too (multi-resistant)

Answer 94

* Knowing that a person is colonised with MRSA means that if they develop an infection which might be caused by Staph aureus, they might need different antibiotics to treat it * MRSA can be spread from person to person, so identifying carriage helps us put measures in place to prevent spread * MRSA carriage is more common in those who have recently been in a healthcare facility eg hospital

Answer 95

* **C**arbapenemase **P**roducing **E**nterobacterales * *Enterobacterales* are a group of Gram-negative bacteria that live in the gut eg E coli, Klebsiella * Carbapenems are very broad-spectrum antibiotics that can resist most of the enzymes that bacteria produce to break down antibiotics * CPE produce a carbapenemase enzyme that breaks down the carbapenem * They are resistant not just to carbapenems but to most antibiotics (multi-resistant)

Answer 96

* Knowing that a person is colonised with CPE means that if they develop an infection which might be caused by Gram negative organisms, they might need different antibiotics to treat it * CPE can be spread from person to person, so identifying carriage helps us put measures in place to prevent spread * CPE carriage is more common in those who have recently been in a healthcare facility in a place where CPE is common – in some other countries and in some parts of the UK (London, Manchester)

Answer 97

* Charcoal swab (black top) * Separate swabs for * Nose (both nostrils) * Throat (back of throat) * Groin (perineum) * Any wounds or device sites * CSU if catheterised * Different hospitals use different combinations * Swabs are plated onto MRSA selective agar and incubated * **This agar contains an indicator dye so staph aureus colonies are green (other skin organisms will be white)** * It also contains antibiotics so selective organisms will be killed and not able to grow

Answer 98

* Rectal swab or stool sample * Stool is better but harder to collect * Red topped swab – for PCR * Charcoal (black topped) swab – for culture * Different hospitals ask for different numbers of swabs spaced apart (often 48 hours) * This can be performed using selective agar for CPE, or by testing the sample directly using PCR or lateral flow * PCR and lateral flow only look for the 5 most common genes which confer resistance * There are many more

Answer 99

* anaerobic, gram positive, spore-forming bacteria which is found in the the guts of healthy people (33%) where it does not cause any symptoms * problem arises when the person becomes unwell or takes broad spec bacteria (wipes out 'good' bacteria) * therefore c.diff is not kept in check and can produce high levles of toxin, which cause clinical disease when in high enough concentrations * ingestion of spores is route of transmission (although recent evidence suggests can also be airborne?) * the spores can remain viable in the environement for long periods of time

Answer 100

* Broad-spectrum antibiotic use * Some more implicated than others- fluoroquinolones, cephalosporins, clindamycin * Acid supressing medications (PPIs) * Increasing age * Hospitalisation * Underlying morbidity particularly immunosuppression * Inflammatory bowel disease * Certain C.difficile strains more associated with severe disease- eg. type 027 * Exposure to other patients with C.difficile and/or contaminated environment (including the hands of HCWs!)

Answer 101

* Symptoms can range from mild self-limiting diarrhoea to pseudomembranous colitis, toxic megacolon, perforation and death * Disease is caused by the toxins produced by C.difficile damaging the lining of the colon * Indicators of disease severity: * WCC \>15 * Acutely rising serum creatinine (AKI) * Fever \>38.5 * Evidence of severe colitis (clinical peritonitis, radiological changes)

Answer 102

* Antibiotics: * Metronidazole (PO or IV) – mild-moderate disease * Vancomycin (PO ONLY) – severe or recurrent disease * Fidaxomicin (PO) – non life-threatening recurrent disease * IVIG with combination of IV metronidazole and oral vancomycin +/- surgical management in life-threatening disease * Faecal transplant in recurrent disease

Answer 103

* Dehydration * AKI * Electrolyte Imbalance * Pseudomembranous colitis * Toxic megacolon * Requirement for colectomy * Colonic perforation * Peritonitis * Death

Answer 104

* Stool sample! * GDH * PCR * Toxin * Interpreting the results: * Not detected * C.difficile CARRIER * C.difficile TOXIN DETECTED

Answer 105

* Address the risk factors! * Antimicrobial stewardship * Review of PPIs/H2-antagonists * Infection control * Not all risk factors are modifiable- age, hospitalisation, need for specific antibiotics

Answer 106

No, catheters quickly become colonised by bacteria but that does not result in clinical infection

Answer 107

* Presence of urinary tract catheter! * Manipulation of catheter, trauma * Negates one of the body’s main defences against UTI: the direction of flow of urine down the urethra which helps wash out bacteria * Biofilm formation on prosthetic material: microbial cells embedded in a sticky extracellular matrix that adheres to a surface. This acts as a source of infection, and can’t be eradicated due to poor penetration of antibiotics **No catheter** ** no CAUTI**

Answer 108

* No urine dipsticks!!! * Chronic bacterial colonisation of a catheter will result in permanently positive dipstick results. This means that the dipstick results will not help with any decision-making process * Urine culture, taken following TWOC/re-catheterisation, or from the catheter port site (NOT the catheter bag) * NB asymptomatic bacteriuria is not diagnostic – **don’t treat a positive urine result in an asymptomatic patient** * Blood cultures (if abnormal temperature/systemically unwell)

Answer 109

* You send a catheter sample of urine (CSU) from the catheter port, and send it to the Microbiology laboratory for culture * On the request form, you include the specimen type, symptoms, and any other relevant clinical details * E.g. recent C.difficile infection, any antibiotic allergies (for example giving antibiotics to someone who has had recent c. diff puts them at high risk for reoccurrence so weight risk verses benefit) * Next day, the culture shows \>100,000 colony forming units of Klebsiella pneumoniae * No sensitivity results are given on the report, so you call the Microbiology department for advice

Answer 110

* Catheter removal or catheter change * Antibiotics, if required: * Look back at previous urine cultures to see if the patient has previous results that help inform the decision * Otherwise, the treat according to local antibiotic guidelines for UTI * 7 days for ‘complicated UTI’ * If systemically unwell: IV antibiotics for urosepsis, rationalise according to culture results

Answer 111

* **Avoidance of urinary tract catheters** * Insertion by properly trained personnel, using good aseptic technique * Unobstructed flow – no kinks in tubing, keep the bag secured below the level of the bladder to avoid backflow, empty drainage bag when necessary * Encourage mobilisation, recognise and treat dehydration, resolve constipation, encourage good hygiene * Removal of catheter when no longer required * Routine catheter changes for long term catheters * Antibiotic prophylaxis not routinely required unless significant previous infection associated with catheter manipulations * Long term antibiotic prophylaxis/methenamine Hippurate – NOT ROUTINELY ADVISED

Answer 112

1. Fixation of specimen to slide (heat or methanol) 2. Application of primary stain **(Crystal Violet)** then rinse 3. Application of mordant (binds stain more tightly- Iodine) then rinse 4. Decolourisation (acetone or ethanol) then rinse 5. Application of counter-stain **(Safranin or Carbolfuschin)** then rinse 6. Blot dry

Answer 113

* Gram positive cocci in clusters * Staph aureus (including MSSA and MRSA) * Gram positive cocci in pairs * Streptococcus pneumoniae * Gram positive cocci in chains * Enterococci * Other streptococci (eg. Group A Strep) * Gram positive rods: * Clostridium perfringens * Gram negative cocci: * Neisseria gonorrhoea * Neisseria meningitidis * Gram negative rods: * Pseudomonas aeruginosa * E.Coli * Klebsiella pneumoniae * Salmonella sp. * Enterobacter sp.

Answer 114

* Endocarditis = Infection and inflammation of the endothelial surface of the heart by a micro-organism. * **Turbulent blood flow can cause damage to smooth surfaces** leading to the accumulation of platelets / fibrin / leucocytes which **can then become infected by any circulating microorganisms and form a vegetation**

Answer 115

* Vegetations

Answer 116

* **Almost any type of structural heart disease** can predispose to IE. Rheumatic heart disease was the most frequent underlying lesion in the past, and the mitral valve was the most commonly involved site * Prosthetic valves and cardiac devices (such as permanent pacemakers and cardioverter defibrillators) * Congenital heart disease * Injection drug use (IVDU) * Human Immunodeficiency Virus infection (particularly if accompanied by immunocompromise) * Extensive health care system contacts

Answer 117

* strep and staph collectively account for 80% of all cases * **The emergence of health care-associated IE has been accompanied by an increase in the prevalence of Staphylococcus aureus and coagulase-negative staphylococci,** whereas the proportion of IE due to viridans group streptococci (VGS) has declined**.** * enterococci are the third leading cause of IE and are increasingly linked to healthcare * infections that involve gram-negative and fungal pathogens in IE are rare

Answer 118

* In approximately 10% of cases of IE, blood cultures are negative * Most commonly due to patient receipt of antibiotics before the diagnostic work-up. * ‘True’ culture-negative IE is caused by fastidious microorganisms that are difficult to isolate with conventional microbiological techniques. * Causes include * Coxiella burnetii (the causative agent of Q fever, associated with abattoirs / livestock) * Bartonella spp (associated with alcoholism or homelessness) * Brucella spp (associated with contact with livestock or abattoirs) * Tropheryma whipplei * Brucella spp (travel to the Middle East or the Mediterranean or consumption of unpasteurized dairy products) * Bartonella henselae (contact with cats) * Aspergillus spp. (extensive health care contact in a patient with a prosthetic valve)

Answer 119

* **Embolic manifestations include (figure):** * Portions of the fibrin–platelet matrix of the vegetation may dislodge from the infected heart valve and travel with arterial blood until lodging in a vascular bed downstream from the heart. (left sided heart disease will result in systemic emboli) (right sided heart disease will cause septic emboli in lungs) * **Immunological manifestations include:** * Skin: findings such as Osler's nodes consist of arteriolar intimal proliferation with extension to venules and capillaries and may be accompanied by thrombosis and necrosis. Immune complexes may be found within the lesions. * Renal: immune complex deposition glomerulonephritis * Systemic: Rheumatoid factor may be raised

Answer 120

* Basic initial investigations on presentation as follows: * Bloods * Inflammatory markers may be raised: CRP, ESR, WCC, Plts * Look for end organ damage/comorbidities: U&E, LFTs * Blood Cultures * **Ideally 3 sets with a period of time between each (1-6 hrs)** * **2 sets within 1 hr if septic and starting antibiotics** * Do not wait for temperature spike – bacteraemia is constant in IE regardless of temperature * ECHO * TTE (transthoracic) or TOE (transoesophageal) (should be low threshold for transoesophageal if TTE is negative due to it being more sensitive)

Answer 121

* Mortality * No treatment 100% * Treatment – 20-25% die

Answer 122

Predisposing heart conditions include valvular heart disease, valve replacement, structural congenital heart disease, previous endocarditis or hypertrophic cardiomyopathy.

Answer 123

**Efficacy and safety of shifting to oral antibiotic treatment was non inferior to continues IV treatment,** in the case of: * In stabilised patients with left-sided endocarditis caused by Streptococcus spp, Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci * Across co-morbidities, native vs prosthetic valve and surgically vs conservatively treatment **Oral antibiotics may safely be administered during approximately half of the recommended antibiotic treatment period** * Potentially as outpatient treatment * More than 50% of patients with endocarditis may be candidates for partial oral antibiotic treatment

Answer 124

* If chronic/subacute presentation: 3 optimally filled sets to be taken from peripheral sites with 6 or more hours in between them prior to antibiotics * If septic shock: 2 optimally filled sets at different times within 1 hour prior to antibiotics

Answer 125

* **Coxiella burnetti (Q fever)** * **Bartonella spp** _Considered_ if these two are negative: * Chlamydia, legionella, mycoplasma Brucella if risk of exposure

Answer 126

Risk factors for enterobacteriaceae, pseudomonas: * **IVDU**, elderly, diabetic

Answer 127

Guidelines suggest antibiotics therapy for at least 4 weeks in NVE, and 6 weeks PVE or patients with secondary lung abscesses and osteomyelitis.

Answer 128

In the treatment of streptococcal endocarditis, the minimum concentration of penicillin to inhibit growth of bacteria is required. Those with high MIC of over 0.5mg/L should be treated as per enterococcal guidelines.

Answer 129

The BSAC guidelines suggest that first line therapy for susceptible enterococci is amoxicillin or high dose penicillin combined with gentamicin. Glycopeptides such as vancomycin and teicoplanin, in combination with gentamicin are second line for susceptible enterococci.

Answer 130

Fungal endocarditis is common in patients with prosthetic valves but also can occur in IVDU, neonates and immunocompromised patients. * Candida infections: usually HCAI, first line is amphotericin * Aspergillus infections: **surgical valve replacement is mandatory for survival,** variconazole is first line with confirmation of susceptibility to variconazole and therapeutic drug level monitoring, (amphotericin B can be an alternative but some species are resistant).

Answer 131

* Fastidious extracellular Gram-negative bacteria, including: * Haemophilus species * Aggregatibacter actinomycetemcomitans * Cardiobacterium hominis * Eikenella corrodens * Kingella kingae * 3% of cases

Answer 132

* Beta lactamases stable cephalosporin or amoxicillin (if isolate is susceptible) * Gentamycin for first 2 weeks of therapy * Ciprofloxacin can be considered an alternative agent

Answer 133

* most common cause of culture negative IE * treatment: * at least 18 months * combination of doxycycline and hydroxychloroquine

Answer 134

* gram negative, causes up to 3% of all IE * transmitted by body louse * RFs include homelessness and alcoholism (quintana) * cat scratch fever * rare cause of endocarditis (henselae) * treatment: * gentamicin in combination with a beta lactam or doxycycline, minimum four weeks

Answer 135

The pathogenesis of DSS is not fully understood, but may be due to immune priming by prior exposure to a different serovar. DSS is a significant problem in endemic areas where people are repeatedly exposed, particularly affecting young children and elderly, but is less common in travellers. These features raise the question of whether his febrile illness in Sri Lanka the year before was also an episode of Dengue Fever.

Answer 136

* **F**ever * **R**oth’s spots * **O**sler’s nodes * **M**urmur * **J**aneway lesion * **A**naemia * **N**ail haemorrhage * **E**mboli

Answer 137

There have been several studies showing a close association between S. gallolyticus (formerly known as strep bovis) endocarditis and colon cancer, with incidence between 18% and 62%. It has been standard of care to screen the patients with S. gallolyticus endocarditis for colon cancer (eg colonoscopy and/or CT scan).