Acute Infection Flashcards
What are the risk factors for patient with Osteomyelitis?
previous osteomyelitis penetrating injury intravenous drug misuse diabetes HIV infection recent surgery distant or local infections sickle cell anaemia rheumatoid arthritis chronic kidney disease immunocompromising conditions upper respiratory tract or varicella infection (in children)
What pathogens can cause meningitis is immunocompromised individuals?
Listeria monocytogenes (unpastureized milk) TB(endemic areas)
What are the risk factors for meningitis?Kernigs and Brudenzski
complement systems defects,hyposplenism,HIV
What investigations should be done in patients suspected of viral mengitis and how are they treated
A polymerase chain reaction (PCR) test for enterovirus, herpes simplex virus 1&2 and varicella zoster virus on the cerebrospinal fluid sample. All patients with meningitis should also be offered a HIV test.
There is no treatment of proven benefit in viral meningitis. Supportive treatment and rest is recommended. Some clinicians advocate using Aciclovir to treat meningitis due to herpes simplex virus but there is no good quality evidence to support this and it results in an increased length of stay in hospital.
Recovery is likely to be slow. Many patients suffer from symptoms including fatigue, headaches, slowed thinking and mental health problems for many months.
How can meningitis be treated and when are steroids given?When is Prophylaxis given?
IV ceftriaxone 2g/12hrs
Pre-hospital
Only in patients with signs of meningococcal sepsis e.g. non-blanching rash
Intramuscular Benzylpenicillin or Ceftriaxone
Hospital
Antibiotics should be given within 1 hour of arrival if meningitis or sepsis are suspected
Ideally, this would be immediately following lumbar puncture and blood cultures
Standard antibiotics recommended for sepsis may not be appropriate
Cefotaxime/ Ceftriaxone (or Chloramphenicol if penicillin allergy)
Duration of antibiotic therapy depends on the causative organism
Modest reduction in mortality in pneumococcal meningitis only
Reduction in risk of hearing loss
Current UK guidelines
Start dexamethasone ideally shortly before but certainly within 12 hours of the first dose of antibiotics
Continue for 4 days only in cases where pneumococcal meningitis is confirmed, or thought probable
Pneumococcal-Signs of meningism present where as meningococcal rash is present
Only recommended for meningococcal infection
Aim - to eradicate nasal carriage of N.meningitidis
Offered to:
Close contacts – living in same house or sharing a kitchen in halls of residence
High risk exposure – exposure to airways secretions e.g. intubation, CPR
Recommended treatment:
Ciprofloxacin oral for a single dose
Rifampicin oral for 2 days
Ceftriaxone intramuscular injection for a single dose
Which factors suggest a poor prognosis from meningitis?
Essentially, these factors reflect the presence of features suggesting the development of complications;
Disseminated intravascular coagulation
Severe sepsis/ septic shock
Raised intracranial pressure
Urgent senior review and critical care assessment is required
What are the complications of meningitis?
Deafness-sensineuronal
Cognitive impairment
Focal neurological deficits
Epilepsy
meningococcal-skin necrosis,amputation,pneumonia,permenant adrenal insufficiency,pericarditis,arthritis,ocular infection
What Vaccinations are given to prevent meningitis
Infants-Capsular group A and B
Quadravent ACWY at age 24 oe high risk travel
What Investigations can be used to diagnose viral encephalitis
Lumbar Puncture
General findings
White blood cells ↑ (lymphocytes)
Protein ↑
Glucose ↔
Specific tests
PCR on cerebrospinal fluid for HSV 1 and 2, VZV and Enteroviruses
Clinical features allow differentiation from viral meningitis
Neuro-imaging
MRI can show evidence of brain parenchyma inflammation
Other tests
EEG – especially to rule out subtle motor seizures or non-convulsive status epilepticus
HIV test – wider investigations are required in immune compromised patients
If relevant travel history – serology and PCR for other neurotropic viruses
What are complication and prognosis of viral encephalitis?
Mortality No treatment ~70% die Treatment - 10-20% die Worse outcomes with delayed treatment >24hrs Acute complications Venous sinus thrombosis Status epilepticus Stroke Aspiration pneumonia
HSV encephalitis is often life-changing
~60% of survivors are left with a permanent neurological disability
Specialist neuro-rehabilitation may be required
Would a negative cerebrospinal PCR test exclude a diagnosis of viral encephalitis?
NO,10% of patients might of a negative serology on initial test, therefore if clinical suspicion remains another PCR should be done 24-48hrs later
To exclude viral Encephalitis -Need to have 2 negative PCR tests done 24 to 48 hours apart and normal MRI
OR
.HSV PCR in the CSF is negative ONCE >72 hours after neurological symptom onset, with unaltered consciousness, normal MRI (performed >72 hours after symptom onset), and a CSF white cell count <5 cells/mm3
What are the Indications and Complications of LP
Indications
Diagnostic
Infection – meningitis (bacterial/ viral/ fungal) or encephalitis
Subarachnoid haemorrhage
Other – multiple sclerosis, malignancy etc.
Therapeutic
Reduce intracranial pressure e.g. idiopathic intracranial hypertension
Spinal epidural
Pain relief (during labour)
Anaesthesia (e.g. lower limb surgery)
Contraindictions
Indications for brain imaging prior to lumbar puncture
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
Infection at the site of the lumbar puncture
How can IE be managed?
Antibiotics as soon as blood cultures taken:
4-6 weeks, including at least 2 weeks IV initially.
Empirical treatment-
NVE,indolent-gentamicin+amoxicillin
NVE,severe sepsis no risk factors for entero-psuedomonas-Vancomycin +gentamicin
If risk factor-Vancomycin+meropenem
Empiric therapy and for streptococci: benzylpenicillin (or amoxicillin) + gentamicin.
Staph. aureus: flucloxacillin if native valve, add rifampicin and gentamicin if prosthetic valve.
Enterococcal-Amoxicillin,amoxicillin +gentamicin,
Surgery:
Debridement, repair, or replacement required in 20%.
Indications: refractory HF, persistent sepsis or emboli, or fungal IE.
Prevention
Prophylactic antibiotics for high-risk dental procedures in patients at risk of IE (e.g. prosthetic valves) is controversial: European and American guidelines recommend it, but NICE do not.
How to diagnose prosthetic valve endocarditis?
Diagnosis is more difficult in PVE than in NVE (native valve endocartitis) and is based mainly on the results of echocardiography and blood cultures. However, both are more frequently negative in PVE. Although TOE is mandatory in suspected PVE, its diagnostic value is lower than in NVE. A negative echocardiogram is frequently observed in PVE and does not rule out the diagnosis, but identification of a new periprosthetic leak is a major criterion, in which case an additional imaging modality could be considered (such as CT or nuclear imaging).
How can prothetic valve endocarditis be treated and what complications can develop
A very high in-hospital mortality rate of 20–40% has been reported in PVE.
These patients need aggressive management, consisting of antibiotic therapy and early radical surgery.
Most common causative Organism in prosthetic valve is staph aureus
antibiotics-Vancomycin and rifampicin and gentamicin
If vancomycin resistant-daptomycin
Several factors have been associated with poor prognosis in PVE including older age, diabetes mellitus, healthcare associated infections, staphylococcal or fungal infection, early PVE, HF, stroke and intracardiac abscess
name other signs and symptoms associated with IE?
Fever Roth’s spots Osler’s nodes Murmur Janeway lesion Anaemia Nail haemorrhage Emboli
Infective Endocarditis caused by which pathogens need a colonoscopy?
There have been several studies showing a close association between S. gallolyticus 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).
Strep bovis
When should a trans oesophageal echo be done?
Echo must be performed ASAP (ideally within 24 hours) in all patients with suspected IE (C)
TTE first (C)
If TTE negative but clinical suspicion, repeat TTE/TOE at 7-10 days (C)
SA bacteraemia/Candidaemia should have TTE within first week of treatment or within 24 hours if other evidence of IE (B)
TTE at completion (C)
F/u Echo if cardiac complications or suboptimal response to treatment (B)
Routine repeat Echo whilst on treatment is not required (C)
How many blood cultures need to be done? and what organisms require serology
Blood cultures taken prior to starting treatment in all cases (B)
ANTT when taking blood cultures (B)
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 (C)
If septic shock: 2 optimally filled sets at different times within 1 hour prior to antibiotics (C)
Bacteraemia is constant in IE (B)
Paired blood cultures (B)
Coxiella burnetti (Q fever) (B) Bartonella spp (B) Consider: Chlamydia, Legionella, Mycoplasma (C) Brucella if risk of exposure (C) Candida Ab/Ag tests are NOT used
What is the criteria for surgery?
Hf
Controlled infection-access for example
Prevention of embolism
How can IE be managed?
Antibiotics as soon as blood cultures taken:
4-6 weeks, including at least 2 weeks IV initially.
Empirical treatment-
NVE,indolent-gentamicin+amoxicillin
NVE,severe sepsis no risk factors for entero-psuedomonas-Vancomycin +gentamicin
If risk factor-Vancomycin+meropenem
Empiric therapy and for streptococci: benzylpenicillin (or amoxicillin) + gentamicin.
Staph. aureus: flucloxacillin if native valve, add rifampicin and gentamicin if prosthetic valve.
Enterococcal-Amoxicillin,amoxicillin +gentamicin,
2-4% IE caused by fungal Infections(neonates,Iv drug users,prosthetic valve,immunosuppressed)
candida Albicans-25%
Other Candida_25%
Aspergillus-25%
Other-25%
Intial treatment-Echnocandin,Lysosomal AmphoterIcin B
Modified after Organism identidied
For candida combination of Sugical and Medical treatment reccomended
2-4% IE caused by fungal Infections(neonates,Iv drug users,prosthetic valve,immunosuppressed)
Aspergillous-Variconazole
Surgery:
Debridement, repair, or replacement required in 20%.
Indications: refractory HF, persistent sepsis or emboli, or fungal IE.
HACEK Group
Fastidious extracellular Gram negative bacteria
3% of cases
Treatment
Beta lactamases stable cephalosporin or Amoxicillin
Gentamicin for first 2 weeks of therapy
Alternative Ciprofloxacin
Prevention
Prophylactic antibiotics for high-risk dental procedures in patients at risk of IE (e.g. prosthetic valves) is controversial: European and American guidelines recommend it, but NICE do not.
What is the POET STUDY?
- According to guidelines we treat left-sided infective endocarditis with intravenous (IV) antibiotics for up to 6 weeks in hospital (sometimes OPAT when available)-OPAT-Outpatient parenteral antibiotic therapies
- Endocarditis is associated with high in-hospital complication- and mortality rates - but mainly in the early phase
- After stabilisation, the patient may be clinically fit enough for discharge but have to remain an inpatient solely to finish a long course of iv antibiotics, rather than back home and their daily lives.
- Longer inpatient stays are associated with increased risk of complications such as Healthcare Associated Infections
- Therefore there was interest in researching whether using oral antibiotics, was a safe and equally effective alternative to IV.
Conclusion
Efficacy and safety of shifting to oral antibiotic treatment was noninferior to continued intravenous antibiotic treatment
- in stabilized 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 Tx
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 to partial oral antibiotic treatment
What are the risk factors for IE?What is the modified dude’s criteria?
Risk factors
Increased turbulent flow:
Valve disease.
Prosthetic valves.
Structural disease: unrepaired PDA, VSD, HCM.
Rheumatic heart disease.
Increased pathogen entry and bacteraemia:
IV drug use.
Haemodialysis
Dermatitis
Chronic disease:
Diabetes
Kidney disease.
Duke criteria
Diagnosis requires any 1 of:
2 major.
1 major plus 3 minor.
5 minor.
Major criteria:
+ve blood culture x2 or persistent.
+ve echo: vegetation, abscess, new regurgitation, or prosthetic valve dehiscence.
Minor criteria:
RF +ve.
Fever
Vascular immune-complex signs.
+ve blood culture (x1).
+ve echo for other abnormality.
What are risk factors and organisms responsible for Osteomyelitis?
Risk factors
Portal for pathogen entry:
Trauma: open fracture or orthopedic surgery.
Surgical prostheses.
IVDU
Diseases:
TB
Diabetes
PVD
Immunosuppression.
Alcoholism
Sickle cell disease.
Pathophysiology
Infection can come from direct/contiguous spread (cellulitis, abscess, trauma, surgery prosthesis), or haematogenous spread, which is commoner in kids, patients with urinary catheters, or TB.
Once infected, leukocytes enter bone, releasing enzymes which cause bone lysis and leave necrotic areas known as sequestra. New bone often forms around this.
Chronic osteomyelitis if >6 months of infection.
Pathogens
Staph. aureusis the commonest cause in most patient groups.
Less common pathogens includeStrep. pyogenes(kids),H. influenzae(kids), Gram negative bacilli (elderly), andPseudomonas aeruginosa(IV drug users).
In sickle cell disease,Salmonellais the commonest cause.
What Organisms can cause IE?
The overall causative agents in IE are well documented and have been relatively stable, based on population-based studies over time. The most common pathogens are listed below; these together with any underlying risk factors indicate the most likely causative organism:[2]
Viridans group streptococci Staphylococcus aureus Enterococci Coagulase-negative staphylococci Haemophilus parainfluenzae Actinobacillus Streptococcus bovis Fungi Coxiella burnetii Brucella species Culture-negative Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella species (HACEK). Patients who develop native valve endocarditis in the absence of intravenous drug use commonly present with viridans group streptococci, enterococci, or staphylococci, with other pathogens being less frequent. Intravenous drug users often present with right-sided valvular involvement and are more likely to have S aureus, streptococci, gram-negative bacilli, or polymicrobial infections.[2]
Prosthetic valve endocarditis is most commonly caused by coagulase-negative staphylococci, S aureus, enterococci, or gram-negative bacilli. It should be noted that early prosthetic valve endocarditis is often caused by Staphylococcus epidermidis.[2]
What is the pathophysiology and clinical presentation of bone and joint infection
Bacteria that enter the bloodstream exist in a free-floating planktonic state. Most osteomyelitis is caused by biofilm-forming bacteria. These bacteria express surface components called adhesins that bind to proteins found in host tissues. Once attached, the bacteria produce a polysaccharide extracellular matrix, forming a biofilm.Once sufficient numbers of organisms are present in the biofilm, a complex system of cell-to-cell signalling develops, known as quorum sensing. This controls further development of the mature biofilm. It may also propagate the spread of infection by controlling separation of fragments of this biofilm which seeds to local sites. Some of the organisms in biofilm are able to enter a dormant state with minimal cellular division. In this state, antibiotics that act on cell division are ineffective.
Clinical presentation is highly variable
Septic arthritis tends to present with the 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
What Investigations can be done for bone and joint infections?
Bedside tests Fever is often absent Blood tests FBC, U&Es, CRP, blood cultures Microbiological tests Joint aspiration, bone biopsy, tissue biopsy, sonication of excised prosthetic material Radiology Plain X-rays, CT scans, MRI scans
How does Disseminated gonococcal infections present?How can they be diagnosed and managed?
Presentation:
- 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
Risk factors:
- Female sex
- HIV infection
- Menses
- Low socioeconomic or educational status
- Pregnancy
- Multiple sexual partners
- SLE
- Complement deficiency
Diagnosis:
- Blood cultures (may be negative)
- Synovial fluid analysis (joint aspirate)
- Gram stain will show inflammatory effusion with neutrophil predominance plus or minus gram negative diplococci
- Culture & sensitivity testing
- NAAT PCR (if available and validated for synovial fluids)
Treatment:
- Intravenous ceftriaxone 2 weeks with appropriate oral switch for further 4 weeks
- Joint drainage for purulent arthritis (may need to be repeated several times)
Of note going back to the original presentation
- Parvovirus B19 infection tends to cause a symmetrical polyarthralgia
- Disseminated gonococcal disease tends to cause an asymmetrical and migratory joint symptoms
- This case highlights the importance of taking a full medical history including sexual history
What Organisms usually cause native and prosthetic joint infections
Native-Stap aureus,strep,clostridium.Neisseria gonorrhea,E-coli
Prosthetic
early-Staph,strep,Enterococci
Late
Coagulase negative staphylococci
How can Acute and Chronic Periprosthetic Infections be differentiated?
Acute-<3 months, acute pain, fever,red swollen joint,Stap,ecoli are the causes
Antibiotics-Courses of antibiotics need to be relatively prolonged
Four weeks for septic arthritis
At least six 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
Osteomyelitis-Flucloxacillin
Management-DAIR(Debridement,antibiotics and implant retention)
Chronic-months to years, present with chronic pain, loosening prosthetic, sinus tracts.Causes include coagulase negative staph
Surgical management-Complete removal of prosthesis in stage 1 and 2
What is PUO/FUO and what are the different types?
Sustained or recurrent pyrexias for ≥3 weeks
No identified cause after evaluation: in hospital for 3 days ≥3 outpatient visits
‘Classic’ Nosocomial Immunodeficient HIV
Possible Classic causes- Infection Abscess Infective endocarditis Tuberculosis Complicated UTI
Geography/travel Melioidosis-Asia,Australia RA SLE Possible Nosocomial causes-Catheters/devices Thrombophlebitis UTI/RTI Drug fevers C.Diff ICU – ventilators, ET tubes, NG tubes Stroke-remodelling of brain tissues
Immunodeficiency-Cell-mediated immunodeficiency Congenital Biologic/immunomodulatory therapies Neutropaenia Haematological disorders Chemotherapy < 500 neutrophils/µl N.B. blunted ‘typical’ inflammatory responses-might not be able to generate purogens N.B. lack of radiological changes
How can FUO be Investigated?
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
What substances can induce a fever and what are the different patterns of fever?
Infectious factors: microbes and microbial products
G- bacteria: Lipopolysaccharide (LPS)/Endotoxin
G+ bacteria: Exotoxins; Peptidoglycans
Viruses
Other microorganisms
Non-infectious factors:
Antigen-antibody complexes
Complement
Non-infectious inflammation-genesis irritants
Drugs – antibiotics, steroids, chemotherapy agents
Fever-inducing cytokines: TNF IL-1 IL-6 IFN Derived from: mononuclear cells macrophages T-lymphocytes Kupffer cells endothelial cells tumour cells
Sustained-Parenchymal and interstital infections -Pneumonia,UTI,Typhoid,Brucelosis
Intermittent-Abcess on lung brain liver ,intermittent sepsis,empyema
Remittent-Active IE,blood stream infections
Relapsing-usually have intervals of 24 to 48 hours for example in malaria,parasitic infections
What causes gas gangrene?
he causative organism is almost always clostridial and is typically Clostridium perfringens.
It is important to note that having a peripheral vascular disease increases the risk of developing gangrene of all causes. C perfringens is a Gram-positive spore-forming bacillus.
What are the causes of enteric fever and how do they present?
Typhoid and paratyphoid are caused by Salmonella typhi and Salmonella paratyphi (types A, B & C) respectively. They are often termed enteric fevers, producing systemic symptoms such as headache, fever, arthralgia
They are aerobic, Gram-negative rods which are not normally present as commensals in the gut.
Features
initially systemic upset as above
relative bradycardia
abdominal pain, distension
constipation: although Salmonella is a recognised cause of diarrhoea, constipation is more common in typhoid
rose spots: present on the trunk in 40% of patients, and are more common in paratyphoid
Possible complications include
osteomyelitis (especially in sickle cell disease where Salmonella is one of the most common pathogens)
GI bleed/perforation
meningitis
cholecystitis
chronic carriage (1%, more likely if adult females)
What is the main risk of Parvo virus infection in pregnancy?
However, potential complications can include hydrops fetalis and fetal death. The risk of these complications is similar in symptomatic and asymptomatic women with parvovirus.
mmediate serological testing for parvovirus B19 is required for all pregnant women in contact with someone with a rash consistent with parvovirus.
How does Infection mononucleosis present?
The classic triad of sore throat, pyrexia and lymphadenopathy is seen in around 98% of patients:
sore throat
lymphadenopathy: may be present in the anterior and posterior triangles of the neck, in contrast to tonsillitis which typically only results in the upper anterior cervical chain being enlarged
pyrexia
Other features include:
malaise, anorexia, headache
palatal petechiae
splenomegaly - occurs in around 50% of patients and may rarely predispose to splenic rupture
hepatitis, transient rise in ALT
lymphocytosis: presence of 50% lymphocytes with at least 10% atypical lymphocytes
haemolytic anaemia secondary to cold agglutins (IgM)
a maculopapular, pruritic rash develops in around 99% of patients who take ampicillin/amoxicillin whilst they have infectious mononucleosis
How can Infectious mononucleosis be diagnosed and managed and what should
Symptoms typically resolve after 2-4 weeks.
Diagnosis
heterophil antibody test (Monospot test) - NICE guidelines suggest FBC and Monospot in the 2nd week of the illness to confirm a diagnosis of glandular fever.
Management is supportive and includes:
rest during the early stages, drink plenty of fluid, avoid alcohol
simple analgesia for any aches or pains
consensus guidance in the UK is to avoid playing contact sports for 8 weeks after having glandular fever to reduce the risk of splenic rupture
What can cause a false positive and false negative Mantoux test?
mmunosuppression can cause a false negative result - including in sarcoidosis, steroid use, AIDS and lymphoma.
False positive-BCG,Immunity to TB
What is the commonest cause of pneumonia post viral infection and it alcoholics?
post viral-Staph Aureus
Alcoholics-Klebsiella
How does Mycoplama present and what are the complications?
Features
the disease typically has a prolonged and gradual onset
flu-like symptoms classically precede a dry cough
bilateral consolidation on x-ray
complications may occur as below
Complications
cold agglutins (IgM): may cause an haemolytic anaemia, thrombocytopenia
erythema multiforme, erythema nodosum
meningoencephalitis, Guillain-Barre syndrome and other immune-mediated neurological diseases
bullous myringitis: painful vesicles on the tympanic membrane
pericarditis/myocarditis
gastrointestinal: hepatitis, pancreatitis
renal: acute glomerulonephritis
Investigations
diagnosis is generally by Mycoplasma serology
positive cold agglutination test
Management
doxycycline or a macrolide (e.g. erythromycin/clarithromycin)
What are the differentials for night sweats?
- Infection: TB, abscess, endocarditis, osteomyelitis, HIV, any other infection.
- Lymphoproliferative disease.
- Drugs: antidepressants, antipsychotics.
- Endocrine: thyrotoxicosis, diabetes.
- Others: menopause, anxiety, idiopathic hyperhidrosis.
What infections can be transmitted by Aedes eygpti mosquito?
Dengue
Chickengunya
zIKA
What are the warning signs of Dengue and signs of DSS
Warning signs-abdominal pain and tenderness,Persistent vomiting and diarrhoea,clinical fluid accumulation,mucosal bleeding,tender hepatomegaly,lethargy,Increase HCT and reduced platelets
Severe Dengue
Plasma leakage
Organ impairment-shockAST/ALT>1000,CNS,heart
Severe bleeding
What drugs should be avoided in Dengue?
NSAIDS and ibuoprofen increases the risk of bleeding.Acetoaminopen(Panadol)and sponging can be used
What are the 3 phases in dengue and it’s importance?
Febrile-dehydration
Critical -plasma leakage, saddle back fever
Convalesce-risk of fluid over load
Pathophysiology-Affects endothelial glycocalyx layer
How can dengue be treated?
Febrile phase=Crystalloid
Critical phase=Crystolloid,(FFP,Albumin,packed red cell,DIVC regime if severe)
Recovery-stop fluid infusion and allow fluid resorption
What Investigations can be done to identify dengue?
naat
RT-PCR
NS1 antigen
ELISA-IgM,IgG serology
< 5days from onset of fever-RT-PCR,NS1 antigen
> 5 days-IgM(recent infection,IgG (past infection)
RT pcr +IgM or IgM + NS1 extend the window of detection to 10 days post fever
What Ultrasound finding may indicate dengue infection?
gall bladder wall thickening
How can rickettsial diseases be classified and what is Scrub typus presentation?
Spotted fever group
Typus
Scrub typus
Scrub typus
An acute, febrile, infectious disease which is caused by the organism Orientia tsutsugamushi.
Source of infection——–Rat
Route of transmission—–Trombiculid mites
Susceptible population—-All susceptible
Spread by haematogenus or lymphatic system
Epidemic features———-Tsutsugamushi triangle
Clinical features
Eschar(inoculation), regional lymphadenopathy, fever, Maculopapular rash, leukopenia
What is the Epidemiology of Scrub typus?
Tsutsugamushi triangle
North: northern Japan and far-eastern
Russia
South: to northern Australia
West: to Pakistan and Afghanistan
How is Scrub typus diagnosed?
Epidemiology data：Visit the endemic area during the past 3weeks. working, camping or sitting on grass
Clinical manifestation：Eschar,regional lyphadenopathy, fever, maculopapular rash, leukopenia, failed therapy with common antibiotic drug.
Laboratory examination：Weil-felix reaction with titers beyond 1:160 or fourfold rise during the course of disease.
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.
Maculopapular rashes
Onset: Appear at the end of the 1st week, lasts 3~7d.
Location: Chest, abdomen, whole trunk, or upper and lower limbs. rarely involves the face, palms and soles. .
Haematology:
Leukopenia
Normal of WBC,
Elevation with some complications.
Biochemical:
Injury of liver function, CRP
Weil-felix: Can be positive as early as 4th day after onset.
>1:160 or increase 4 times during the course.
Easy for operation but poor for specialization.
IFA (Indirect Fluorescent Antibody): Almost the gold standard.
Positive at the end of the 1st week. Last for years.
IIP (Indirect Immunoperoxidase Test): Comparable to those from IFA. More available.
Culture: Mouse is usual experimental animal.
Spleen and liver are stain with Giemsa.
PCR: Detect the orientia DNA
Not routinely available
How can Scrub typus be treated and prevented?
Ddx-Epidemic typhus: occur 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 of typhus bacillus is positive.
Leptospirosis: Tenderness of calf muscle, microscopic haematuria
Treatment
Sensitive antibiotics decrease fatality from as high as 30 % (untreated) to 2%.
General treatment
Supportive IV Fluids
Intensive nursing care and prevent complication
Chloramphenicol : 2g per day for adult, or 25mg/kg of bw per day for children.
Doxycycline: 0.2g per day for adult. (tetracycycline 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
Prevention
Source of infection: Rat
Routes of transmission: Trombiculid mite
Protect succeptibility: Avoid being bitten
No effective vaccine against scrub typhus
Prophylactic antibiotics ? Only in special situations perhaps! Few evidence
What are the examples for healthcare associated infections?
C.difficile MRSA CAUTI MSSA bacteraemia Indwelling catheter (line) related infections HAP and VAP Surgical site infections GI infections eg. norovirus as part of an outbreak Candida auris CPE (carbapenemase producing enterobacteriaceae) Antimicrobial resistance- others ESBL GRE/VRE
Other transmissible infections: MDR/XDR TB VHFs (eg. Lassa fever, Ebola) SARS/COVID-19/MERS vCJD BBVs (hepatitis B/C, HIV)
- Healthcare environments can be a reservoir for organisms which have the potential to cause health care associated infections (HCAIs)
- HCAIs are associated with increased morbidity and mortality and are estimated to cost the NHS around £2.7 billion per year. (1)
- Therefore imperative to have collaborative working between designers, architects, engineers, facilities managers and the infection and prevention control (IPC) teams to create a safer environment for patients and staff.
What are the legislations in place for safety and infection control in inbuilt environment such in hospitals and who is responsible?
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)
HTMs-Comprehensive advice and guidance on the design, installation and operation of specialised building and engineering technology used in the delivery of healthcare.
HBNs-Building note detailing each stage of a project, from initial concept through to post-project evaluation, in relation to infection control.
IPC team including DIPC (Director of Infection and Prevention Control) Microbiologists Domestic team Estates team including engineers Architects
Members from each team meet to discuss, monitor and improve infection control in various areas, such as water and ventilation.
Why is proper ventilation in a health care setting needed and what are different systems?
Important to have appropriate ventilation to prevent airborne infections
Airborne transmission
Spread of an infectious agent caused by the dissemination of droplet nuclei/aerosols (≤5μ) that remain infectious when suspended in air over long distances and time (vs contact or droplet transmission >5-10μ)
Ventilation is a means of removing and replacing the air in a space
Dilution of contaminants
Clean airflow path
Control of Hazards-removal of gases moisture,odors
Comfort
Clean air flow paths
positive (neutropenic)and negative pressure rooms(infection)
Ultra clean ventilation
What Infections can be transmitted from water and what are water safety groups?
Pseudomona’s
Team of specialists 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
What does MRSA cause and how is it screened?
Meticillin Resistant Staphylococcus aureus
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 meticillin – and hence also flucloxacillin
It is often resistant to other antibiotics too (multi-resistant)
Screening 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 sensitive organisms will be killed and not able to grow
How is CPE
Carbapenemase Producing Enterobacterales
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)
Screening
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 many more
What are the risk factors for c.difficle and how does it present?
risk factors
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!)
presentation
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)
How is C.difficle investigated and managed?
INx
Stool sample! GDH(Glutamate dehydrogenase-antigen produced by c.difficle) PCR Toxin Interpreting the results: Not detected C.difficile CARRIER C.difficile TOXIN DETECTED
Management
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
Prevention
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
Complications
Dehydration AKI Electrolyte Imbalance Pseudomembranous colitis Toxic megacolon Requirement for colectomy Colonic perforation Peritonitis Death
What are the Indications for Urinary catheterisation?What are risk factors for CAUTI?
Indications
Acute Urinary retention (causes-drugs,nerve injury)
Bladder Outflow Obstruction-Prostatitis,blood clots
Clinical unwell-fluid balance and monitering of urine output
Healing of sacral and perineal wounds
End of life
Prolonged Immbolization-Pelvic fractures
Peri operative-short term
Risk factors
Risk factors
- 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
How can be diagnosed?
Can be difficult to diagnose: the presence of the catheter means that the patient doesn’t develop frequency or dysuria
New onset or worsening of fever, rigors, altered mental status, malaise, or lethargy – with no other identified cause
Flank/loin pain, pelvic discomfort, costovertebral angle tenderness
Acute haematuria
Risk of progressing to urosepsis
NB: dark/cloudy/smelly urine can indicate dehydration rather than UTI
NB: “Purple urine bag syndrome”
Usually a benign condition associated with colonisation of specific bacteria (e.g. Providencia spp)
Indirubin (red) and indigo (blue) are produced from metabolites of dietary tryptophan
May indicate CAUTI, especially in the context of constipation
INX
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/recatheterisation, 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)
How can CAUTI be managed and prevented?
Treatment
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, 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
Prevention
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
Give some examples od
a) gram positive cocci in clusters, pairs,chains
b) gram postive rods
c) gram negative cocci, rods
Gram positive cocci in clusters
Staph aureus (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.
How can CLED agar be used to differentiate bacteria
eg. CLED agar differentiates lactose-fermenting bacteria (eg. E.Coli-yellow) from non-lactose fermenting bacteria (eg. Proteus-green)
What is the use of E tests?
E tests
Combine disc diffusion and ability to generate MIC data
MIC = minimum inhibitory concentration. More specific than disc testing.
MICs may be useful in deciding which antibiotic to use for planned long courses for deep infections
Eg we use penicillin MIC data of streptococci causing endocarditis to know when to use penicillin or amoxicillin and when to avoid them and use an alternative agent.
What Malarial parasites have a dormant stage in the liver?
Vivax and oval-Can cause relapse
What is the life cycle of malaria?
Sporozoites injected through human skin by female anopheline mosquito, then migrate to liver.
In the hepatocytes, they multiply into merozoites. After 1-4 weeks incubation, the hepatocytes rupture and the merozoites are released into the blood.P. vivaxandP. ovalecan also become hypnozoites, incubating in liver for months or even years.
Enter RBCs and become trophozoites then schizonts, which form further merozoites, leading to rupture and hence haemolysis and fever in 48-72 hr cycles.
Some merozoites become gametocytes, which are taken up in RBCs by mosquitoes feeding on blood.
P. falciparumis the most pathogenic as it affects all RBC ages, including reticulocytes, while others only affect mature RBCs
What are the signs and symptoms and complications of malaria?
Epidemiology of cases imported to UK
1500 cases annually, many from those visiting family members in country of origin.
Species:
P. falciparum: 80%, usually Africa.
P. vivax: 10%, usually South Asia.
P. ovaleandP. malariae: 10%.
Signs and symptoms
General:
Fever: all tertian (48-hourly) except quartan (72-hourly) inP. malariae. These classic patterns aren’t always clearly seen.
Rigors
Headache
Diarrhoea and vomiting.
Hepatosplenomegaly
Falciparum malaria:
Flu-like prodrome: myalgia, malaise, headache, anorexia.
Irregular fever initially.
Jaundice
Complicated falciparum malaria:
Mortality approaches 100% if severe and untreated.
Cerebral malaria: altered mental status, seizures, coma, decerebrate posturing, ↑plantars, teeth-grinding.
AKI
Bleeding: haemoglobinuria (‘blackwater fever’), DIC, retinal haemorrhages.
Metabolic: ↓glucose, metabolic acidosis, Kussmaul’s breathing.
ARDS and pulmonary oedema.
Splenic rupture.
Shock
What Investigations are used to diagnose malaria?
Diagnosis using blood films:
Serial testing: up to 3 times if 1st -ve.
Thick film – quick yes or no malaria – and thin film – which subtype.
Also shows parasitaemia (%RBCs infected) and stage, with imminent decline in patient condition due if there are ↑schizonts. Dangerous if parasitaemia >2% and life-threatening if >5%.
Simple but less sensitive antigen detection kits are available too.
Immunochromographic RDT
Quantitative buffy coats
Antibody detection using immunoassays or fluorescence techniques
Bloods:
FBC: anaemia, ↓platelets. Low platelets result from increased splenic activity during haemolysis, leading to excess platelet clearance., low wbc
Coag: DIC.
↓Glucose
ABG: metabolic acidosis.
U+E: AKI.
Other tests:
Urinalysis: blood.
Blood cultures to rule out bacterial sepsis
How can malaria be treated and what chemo prophylaxis is given?
Treatment
Artemether-lumefantrine: 4 tablets then 4 tablets at 8, 24, 36, 48 and 60 h
Atovaquone/proguanil (Malarone): 4 ‘standard’ tablets daily for 3 days.
Quinine sulphate 600 mg 8 hourly for 5 - 7 days plus doxycycline 200 mg daily (or clindamycin 450 mg 8 hourly for pregnant women) for 7 days
P. vivax,P. ovale, andP. malariae: chloroquine plus primaquine.
UncomplicatedP. falciparum: 1st-line artemether/lumefantrine (Riamet). 2nd-line: quinine/doxycycline (quinine/clindamycin in kids), or atovaquone/proguanil.
ComplicatedP. falciparum(cerebral, renal, or shock): artesunate IV (preferably), or quinine IV + doxycycline IV/PO. Careful monitoring of fluid, lactate, U+E. Transfuse if anaemic.
Prophylaxis
Start 1 week before to check for side effects, and continue until 4 weeks after.
Areas without chloroquine resistant falciparum:
Chloroquine (daily) plus proguanil (weekly).
Areas with chloroquine resistance. Any 1 of:
Atovaquone/proguanil (Malarone). Few side effects, and is taken from 1 day before until 7 days afterwards. Expensive.
Doxycyline
Mefloquine (Lariam): once weekly.
Causal
Directed against hepatic stage (i.e. schizonts, not hypnozoites)
Prevents progression to erythrocytic 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, doxycycline, mefloquine Also:
Long sleeves dusk till dawn.
Mosquito nets
DEET repellent.
What are side effects of anti malarial drugs?
Antimalarials
Mechanism
Most prevent plasmodium conversion of haem to inert haemozoin, causing toxic haem accumulation
Primaquine is the only agent effective against hypnozoites.
Side effects
Chloroquine: headache, psychosis, retinopathy. Contraindication: epilepsy.
Primaquine: epigastric pain, triggers hemolysis in G6PD deficiency (check 1st and give atovaquone/proguanil if +ve).
Atovaquone/proguanil: abdo pain, nausea, dizziness.
quinine-Cardiac toxicity – ECG monitoring
Cinchonism-tinnitus, vertigo, N&V, visual disturbances
Mefloquine: nausea, dizziness, insomnia, vivid dreams, psychosis. Contraindications: epilepsy, psychosis.
Doxycycline: photosensitivity, diarrhoea, oesophagitis.
How can malaria be classified according to severity?
UNCOMPLICATED: All of the following
Parasitaemia <2% No schizonts
No clinical complications
POTENTIALLY SEVERE: Any of the following
Parasitaemia >2%
Parasitaemia <2% with schizonts
Parasitaemia <2% with complications
SEVERE
Complications present, regardless of parasitaemia
Who gets leptospirosis, how does it present and how is it managed?
Leptospirosis is caused by the spirochaete Leptospira interrogans (serogroup L. icterohaemorrhagiae), classically being spread by contact with infected rat urine.
Epidemiology
leptospirosis is commonly seen in questions referring to sewage workers, farmers, vets or people who work in an abattoir
however, on an international level, leptospirosis is far more common in the tropics so should be considered in the returning traveller
Weil’s disease should always be considered in high-risk patients with hepatorenal failure
Features
the early phase is due to bacteraemia and lasts around a week
may be mild or subclinical
fever
flu-like symptoms
subconjunctival suffusion (redness)/haemorrhage
second immune phase may lead to more severe disease (Weil’s disease)
acute kidney injury (seen in 50% of patients)
hepatitis: jaundice, hepatomegaly
aseptic meningitis
Investigation
serology: antibodies to Leptospira develop after about 7 days
PCR
culture
growth may take several weeks so limits usefulness in diagnosis
blood and CSF samples are generally positive for the first 10 days
urine cultures become positive during the second week of illness
Management
high-dose benzylpenicillin or doxycyclin
