Mirco: Resp, Gastro and Infective Endocarditis Flashcards
S. Pneumonia
+ve diplococci
a-haemolytic
Rusty-coloured sputum. Usually lobar on CXR. Almost always penicillin sensitive.
30-50% CAP
H. influenzae
-ve cocco-bacilli
Smoking, COPD
15-35% CAP
More common with pre-existing lung disease.
May produce beta-lactamasde.
M. catarrhalis
-ve coccus
Smoking
S. aureus
+ve cocci in “grape-bunch clusters”
Recent Viral Infection (post influenza infection in EMQs), ± cavitation on CXR
K. pneumoniae
-ve rod
Alcoholism, Elderly, haemoptysis
Legionella pneumophila
Travel, Air Conditioning, Water towers, Hepatitis, Low sodium
Can cause multi-organ failure
Confusion, abdo pain, diarrhoea. Lymphopenia and hyponatraemia.
Dx - urinary antigens
Requires special culture: buffered charcoal yeast extract
Mycoplasma pneumonia
Common – systemic symptoms, joint pain, cold agglutinin test, erythema multiforme. Risk SJS, AIHA
Chlamydia pneumonia
Hard to diagnose
Chlamydia psittaci (psittacosis)
Birds - inhalation
Splenomegaly, rash, haemolytic anaemia
Dx by serology
Sensitive to macrolide
Bordatella pertussis
Whooping cough in unvaccinated – (often travelling community in EMQs)
Rx - Classical mild-moderate pneumonia
Penicillin e.g Amoxicillin or macrolide if pen allergic (5-7 days)
Rx - Classical moderate-severe pneumonia
Penicillin + Macrolide ( e.g Co-amoxiclav + Clarithromycin) (2-3 weeks)
Allergic: Cefuroxime AND clarithromycin.
Rx - Classical HAP
1st Line: Ciprofloxacin ± Vancomycin
2nd Line/ITU: Piptazobactam + Vancomycin (ITU pts increased risk of resistant bacteria/MRSA)
Rx - HAP - Pseudomonas
Piperacillin+tazobactam (tazocin/piptazobactam) or Ciprofloxacin ± Gentamicin
Rx - HAP - MRSA
Vancomycin
Rx - Atypical Pneumo - Chlamydia, mycoplasma
Macrolide (e.g. Clarithromycin/erythromycin)/tetracycline (e.g. doxy)
(20% CAPs)
Rx - Aspiration Pneumonia
Cefuroxime and metronidazole
Rx - CAP - Legionella
Macrolide + rifampicin
Rx - CAP - S.aureus
Flucloxacillin
Score for Pneumonia Severity
Curb-65
Confusion Urea >7 mmol/l RR >30 BP <90 systolic <60 diastolic >65 years
Score 2 = ?admit
Score 2-5 = manage as severe
Compromise to resp defences
- Poor swallow
- Abnormal ciliary function e.g. smoking, viral infection, kartagener’s
- Dilated airways - bronchiectasis
- Defects in host immunity
Resp Pathogens by age
0-1 mths- E.coli, GBS, Listeria
1-6mths- Chlamydia trachomatis, S aureus, RSV
6mths-5yrs- Mycolpasma, Influenza
16-30yrs-M pneumoniae, S pneumoniae
Bronchitis
Inflammation of medium sized airways (smaller lumen).
Mainly in smokers
S. pneumoniae
H. influenzae
M. catarrhalis
Coxiella Burnetii (Q fever)
- Common in domestic/farm animals
- Transmitted by aerosol or milk
- Dx by serology
- Sensitive to macrolides
Pneumonia failure to improve on treatment
Empyema / abscess
Proximal obstruction (tumour)
Resistant organism (incl. Tb)
Not receiving / absorbing Abx
Immunosuppression
Other diagnosis
- Lung cancer
- Cryptogenic organising pneumonia (type of idiopathic intersitial pneumonia w/fibrosis)
TB - Clues
Clues:
- Ethnicity
- Prolonged prodrome
- Fevers
- Weight loss
- Haemoptysis
TB - CXR
Classically upper lobe cavitation but can vary considerably
Ghon focus/complex
Occasionally milliary
TB - Stains
Auramine and ziehl Neelsen (counter stain with methylene blue)
Most common causes of HAP (organisms)
Staphylococcus aureus - 19%
Enterobacteriaciae - 31%
Pseudomonas spp - 17%
Pneumocystis Jirovecii
Protozoan
Ubiquitous in environment
Insidious onset
Dry cough, weight loss, SOB, malaise
CXR “bat’s wing” - bilateral ground glass shadowing
Dx Immunofluorescence on BAL (bronchoalveolar lavage)
Rx Septrin (Co-trimoxazole)
Prophylaxis Septrin
Aspergillus Fumigatus Lung Diseases
Allergic bronchopulmonary aspergillosis:
- Chronic wheeze, eosinophilia
- Bronchiectasis
Aspergilloma:
- Fungal ball often in pre-existing cavity
- May cause haemoptysis
Invasive aspergillosis:
- Immunocompromised
- Rx Amphotericin B
Immunosuppression & LRTI
HIV: PCP, TB, atypical mycobacteria
Neutropenia: fungi e.g. Aspergillus spp
Bone marrow transplant: CMV
Splenectomy: encapsulated organisms
e.g. S. pneumoniae, H. influenzae, malaria
BUT “Anything can do anything”
Antigen Tests - Pneumonia
Limited urine antigen tests available:
- S. pneumoniae
- Legionella pneumophila
Send in severe community-acquired pneumonia
Antibody Tests - Pneumonia
Only useful on paired serum samples
Usually collected on presentation and 10-14 days later
Look for rise in antibody level over time
Most useful for organisms that are difficult to culture eg:
- Chlamydia
- Legionella
The only organism (pneumonia) for which immunofluorescence is routinely used
Pneumocystisis jirovecii
May also be detected by Silver stain in cytology lab
Prevention of pneumonia
Smoking advice
Vaccination: - Childhood immunisation schedule. - Adults: Influenza annually Pneumovax every 5 years
Pulmonary TB - Sx
FLAWS
+/- cough
+/- haemoptysis
Pulmonary TB - RFs
Recent Migrant HIV Homelessness IVDU Immunosuppression Foreign travel Living closely with people
Pulmonary TB - Ix
Imaging: CXR (Upper lobe cavitation typically). CT
Culture – Sputum (x3), bronchoalveolar lavage (BAL), urine (EMU - early morning urine), pus etc in Lowenstein-Jensen medium (Gold Standard)
Sputum microscopy – ZN/auramine staining: Gram +ve rods, acid fast, aerobic, intracellular
Tuburculin skin tests (TST): Mantoux/Heaf using PPD
IGRA: interferon-γ release assays e.g. Elispot, Quantiferon - used for screening/diagnosing latent TB NOT active.
NAAT: PCR-line probe assays, tests for sensitivities (more sensitive than culture)
Other: Liquid culture mediums
TB - Vaccination
Vaccination: BCG (=Bacille Calmette-Guerin)
Attenuated strain of M. Bovis
Efficacy 0-80% – Bad for pulmonary TB. Good for leprosy, TB meningitis, disseminated TB.
Extrapulmonary TB
All the “ITIS”
Pericarditis, Lymphadenitis, Peritonitis etc
TB Meningitis
- FLAWS + Neurological change
- Diagnose with CT and LP
- Needs 1yr TB tx with Steroids (PP says 10 months?)
Pott’s Disease aka Spinal TB
FLAWS
Hematogenous spread –> initial discitis –> Vertebral destruction + collapse ± Anterior extension (causing iliopsoas abscess)
Ix – MRI/CT ± Biopsy/Aspirate
Rx – 1 year anti TB treatment
Pulmonary TB - Rx
RIPE 6 months (pp says 4?): Rifampicin - raised transaminases, induces CYP450, orange secretions Isoniazid (+pyridoxine) - peripheral neuropathy, hepatotoxicity
2 months:
Pyrazinamide - hepatotoxicity
Ethambutol - visual disturbance (check colour visitant every review)
+ vit D, nutrition, surgery
M. Leprae & M. Lepromatosis
SNEB
Skin: Depigmentation, macules, plaques, nodules, ulcers
Nerves: Thickened nerves, sensory neuropathy
Eyes: Keratitis, Iridocyclitis
Bone: Periositis, aseptic necrosis
M. Avium (part of M avium complex with M. intracellulare)
Children – Pharyngitis/cervical adenitis
Pulmonary – Underlying lung disease (resembles TB)
Disseminated – Lymphoma etc
AIDS – Disseminated infection, Mycobacteraemia (consider in HIV pts with longstanding diarrhoea)
M. Marinarum
- Single or clusters of papules/plaques –> granulomas
- Swimming pool/aquarium owners
M. Ulcerans
- Insect Transmission / Bite
- Early – painless nodule
- Usually slowly progressive leading to ulceration, scarring + contractures –> Bairnsdale ulcer, Buruli ulcer
- Seldom fatal, hideous deformity
MTB complex includes
M. tuberculosis
M. bovis
M. abscessus complex includes
M.abscessus
M.massiliense
M.bolletii
Mycobacteria microbiology
Non-motile rod-shaped bacteria
Relatively slow-growing compared to other bacteria
Long-chain fatty (mycolic) acids, complex waxes & glycolipids in cell wall
- Structural rigidity
- Complete Freund’s adjuvant
- Staining characteristics
Acid alcohol fast
“Rapid Growing” NTM
M. abscessus, M. chelonae, M. fortuitum
Skin & soft tissue infections
- Tattoo associated outbreaks
In hospital settings, isolated from BCs
- Vascular catheters & other devices
- Plastic surgery complications
NTM - RFs
- Age
- Underlying illness/condition (particularly resp)
Diagnosis of NTM
Lung disease
Clinical: pulmonary symptoms, nodular/cavitary opacities, multifocal bronchiectasis with multiple small nodules
Exclusion of other diagnoses
Microbiologic:
- Positive culture >1 sputum samples
- OR +ve BAL
- OR +ve biopsy with granulomata
NTM - Rx
Susceptibility testing results may not reflect clinical usefulness
MAI (mycobacterium avium)
- Clarithromycin/azithromycin
- Rifampicin
- Ethambutol
- +/- Amikacin/streptomycin
Rapid-growing NTM- Based on susceptibility testing, usually macrolide-based
Close contact of a person with smear positive pulmonary TB, What is his lifetime risk of developing active TB?
10%
Post-primary TB
Reactivation or exogenous re-infection
> 5 years after primary infection
5-10% risk per lifetime
Risk factors for reactivation
- Immunosuppression
- Chronic alcohol excess
- Malnutrition
- Ageing
Clinical presentation
- Pulmonary or extra-pulmonary
Other Extra-Pulmonary TB
Lymphadenitis
- AKA scrofula
- Cervical LNs most commonly
- Abscesses & sinuses
Gastrointestinal
- Swallowing of tubercles
Peritoneal
- Ascitic or adhesive
Genitourinary
- Slow progression to renal disease
- Subsequent spreading to lower urinary tract
Where has the most MDR TB?
Russia
China
India
Drug Resistant TB
Multi-drug resistant TB (MDR)- Resistant to rifampicin & isoniazid
Extremely drug-resistant TB (XDR)- Also resistant to fluoroquinolones & at least 1 injectable
Spontaneous mutation + inadequate treatment
RFs:
- Previous TB Rx
- HIV+
- Known contact of MDR - TB
- Failure to respond to conventional Rx
- > 4 months smear +ve/>5 months culture +ve
4/5 drug regimen, longer duration - Quinolones, aminoglycosides, PAS, cycloserine, ethionamide
Influenza A virus - Hosts
Many different host species - birds, pigs etc
Influenza Tropism
Causes resp disease because:
1) The host cell receptor (sialic acid) the virus binds to is only expressed in the lung
2) The influenza virus can only get into the body through the mouth
3) The influenza virus requires activation by host cell proteases that are only expressed in the respiratory tract - human airway tryptase
4) The influenza virus envelope can only fuse with membranes of cells that secrete mucus.
Host range barriers prevent infection of humans with most avian influenza, however, infection of humans with H5N1 avian influenza viruses can lead to
hypercytokinaemia –> ARDS
Key Features of Pandemic Flu
A pandemic virus will have novel antigenicity.
A pandemic virus will replicate efficiently in human airway.
A pandemic virus will transmit efficiently between people.
AIV (avian flu) replication in mammals can be achieved by a single amino acid change in polymerase
PB2 E627K
Avian influenza viruses co-opt ANP32A to support RNA replication but cannot utilize shorter mammalian ANP32 homologues unless they mutate PB2. However Reassortment/polymerase adaptation is not sufficient for evolution of a pandemic virus.
Features of HA and NA that affect influenza transmission
Receptor binding
Virion stability
NA stalk length
Genetic determinants of influenza susceptibility
Loss of IFITM3 linked with severe influenza.
Antivirals for Influenza
Amantadine
- Targets M2 ion channel
- Single amino acid mutation in M2 (S31N) renders virus resistant
- Does not work against influenza B or pH1N1 or seasonal H3N2
Neuraminidase inhibitors and mode of administration:
- Tamiflu (oseltamivir) oral
- Relenza (zanamivir) inhaled or iv formulation
- Peramivir iv
Polymerase inhibitors:
- Favipiravir (licensed in Japan excluding pregnant women)
- Baloxavir (licensed in Japan) - inhibits the PA endonuclease (decreased virus shedding may interrupt transmission)
Tamiflu
Conflicting evidence
In adults oseltamivir reduced time to first alleviation of symptoms by 16.8 hours, in children by 29 hours.
“no evidence.. to use these drugs to prevent serious outcomes in annual influenza and pandemic influenza outbreaks….”
1/2 mortality if NAI given within 48 hours of symptom onset.
UK adult flu vaccine is
live attenuated
Influenza vaccines in use today - 2 types
Trivalent or quadrivalent inactivated vaccine
- Split or subunit- HA rich
- Given to those at risk
- Short term strain specific immunity mediated by antibody to HA head
- Adjuvants introduced to boost response in elderly
Live attenuated vaccine, quadrivalent
- Cold adapted virus limited to urt
- Given to children
- Broader more cross reactive immunity including cellular response
Novel oil-in-water adjuvants used in monovalent vaccines AS03 Pandemrix have been associated with
Narcolepsy (H1N1-related)
Clostridia - Botulinum
Canned/vacuum packed foods: Blocks Ach release from peripheral nerves –> DESCENDING paralysis
Descending paralysis - differentiates from GBS
Rx - antitoxin
Clostridia - Perfringens
Reheated meats
Enterotoxin (super antigen) acts on small bowel, 8-16hrs incubation.
Watery diarrhea +cramps, lasts 24hrs.
Can also cause gas gangrene
Clostridia - Difficile
2 exotoxins (A,B) Pseudomembranous colitis (i.e an inflamed bowel) Caused by Abx usually cephalosporins, cipro and clindamycin
Rx - 1st line metronidazole PO, 2nd line vancomycin PO. Also infection control - need to be in side room, hand washing with soap and water (gel doesn’t kill spores)
Bacillus cereus
Gram +ve rod-spores
Heat stable emetic toxin (not destroyed by reheating)
Reheated rice
4-18 hours incubation
Watery non-bloody diarrhoea + Vomiting
Self limiting
Rare cause of bacteraemia in vulnerable populations - can cause cerebral abscesses
S. Aureus
Catalase and coagulase positive gram +ve coccus
Produces enterotoxin (exotoxin that acts as superantigen, releasing IL1 and IL2 –> prominent vomiting + watery, non bloody diarrhoea)
Self-limiting
Enterotoxigenic E.coli (ETEC)
Travellers diarrhoea
Act on the jejeunum, ileum not on colon.
Enteroinvasive E.coli (EIEC)
Invasive, dysentry (cramps, D&V)
Enterohaemorrhagic E.coli (EHEC)
haemorrhagic O157:H7 EHEC: shiga- like verocytotoxin causes HUS
Enteropathogenic E.coli (EPEC)
Infantile diarrhoea (paeds)
Haemolytic uraemia syndrome
Anaemia, thrombocytopenia, renal failure
E.coli 0157:H7)
E.colis - Rx
Self limiting - can treat with ciprofloxacin but tend to avoid abx
Source - human faeces, contaminated food/water
(Gram -ve enterobacteriacae)
Salmonella - Typhi and Paratyphi (enteric fever)
Only transmitted by humans
Multiplies in Peyers patches,
Slow onset fever + CONSTIPATION, relative bradycardia
Splenomegaly and rose spots, anaemia and leukopaenia.
bacteraemia in 3% carriers.
Rx- ceftriaxone or ciprofloxacin
Salmonella - Enteritides
Poultry, eggs and meat
Self limiting non-bloody diarrhoea
Rx- usually none. Ceftriaxone or ciprofloxacin (if required)
Shigella
Mainly affects the distal ileum and colon –> mucosal inflammation, fever, pain, bloody diarrhoea, shiga enterotoxin
Avoid abx (cipro if required)
Yersinia enterocolitis
Associated with farming/ domestic animal excreta – transmitted via contaminated food.
Enterocolitis, mesenteric adenitis w/ necrotising granulomas, assoc reactive arthritis & eythema nodosum.
Vibriosis - Cholera
(comma shaped, late lactose fermenters, oxidase +ve)
Rice water stool.
Massive diarrhoea without inflammation.
cAMP: opens Cl channel at the apical membrane of enterocytes»_space; efflux of Cl to lumen; loss of H2O and electrolytes
Rx - supportive
Vibriosis - Parahaemolyticus
(comma shaped, oxidase +ve)
Ingestion of raw undercooked seafood (common in Japan)
3/7 of diarrhoea which is often self limiting
Rx- Doxycycline
Vibriosis - Vulnificus
(comma shaped, oxidase +ve)
Cellulitis in shellfish handlers
Fatal septicaemia with D&V in HIV patients
Rx - doxycycline
Campylobacter Jejuni
(curved, comma or S shaped)
Unpasteruised milk, poultry
Prodrome of headache and fever, cramps, bloody (foul-smelling) diarrhoea
**Assoc with Guillain-Barre, reactive arthritis (Reiter’s)
Only teat if immunocompromised - Erythromycin or Cipro if first 4-5/7
Listeria Monocytogenes
V or L shaped, ß haemolytic with tumbling mobility
Unpasteruised dairy, vegetables
GI watery diarrhoea, cramps, headache, fever, little vomiting.
Rx - Ampicillin, Ceftriaxone, Cotrimoxazole
Entamoeba Histolytica
Protozoa
EMQ: MSM
Also: food, water, soil
Colonizes colon - Makes a flask-shaped ulcer on histology
Mature cyst has 4 nuclei
Symptoms: dysentery, wind, tenesmus. Chronic weight loss + RUQ pain due to liver abscess
Stool microscopy for dx (wet
mount, iodine and trichrome)
Rx- Metroniazole + Paromomycin if luminal disease
Giardia lamblia
EMQ: Travellers/hikers/MSM/ psych hospitals
Pear shaped trophozoite 2 nuclei Trophozoites/cysts found in stool
Get it by ingesting cysts from faecally contaminated H2O
Malabsorption of protein + fat - foul smelling non-bloody diarrhoea
Dx = ELISA + stool microscopy, “string test”
Rx - metronidazole
Cryptosporidium Parvum
Infects the jejunum.
Severe diarrhoea in immunocompromised.
Dx = Oocysts see in stool by Kinyoun acid fast stain
Rx - Paromomycin
Nitazoxanide in kids, reconsistution of immune system
Viruses: Secretory Diarrhoea
Adenovirus – Types 40,41 cause non bloody diarrhoea (<2yrs)
Rotavirus - <6yrs. dsDNA “wheel like”. Replicates in mucosa of small intestine. Secretory diarrhoea, no inflammation.
Norovirus – Adult outbreaks, vomiting.
Other
3 organisms causing bloody diarrhoea
hang on a bloody SEC
Shigella
E.coli
Campylobacter
Superantigens
MOA - secretory diarrhoea - toxin production
Superantigens bind directly to
T-cell receptors and
MHC molecules;
outside the peptide binding site
> > massive cytokine production by CD4 cells ie systemic toxicity and suppression of adaptive response
Inflammatory Diarrhoea vs Enteric Fever
Inflammatory - exudative diarrhoea
Enteric fever - interstitial inflammation
GI Vaccines
Cholera
- Inactivated, whole cell (PO)
- Live attenuated (PO) not recommended
Campylobacter- military, infants,traveller, candidate vaccines exist..
ETEC- inactivated and live vaccines in trials
Salmonella typhi- Vi capsular PS (IM) and (PO)live
Rotavirus - various PO options
GI - Notifiable diseases
Campylobacter, Clostridium sp, Listeria monocytogenes, Vibrio, Yersinia
UTI - Common Organisms
Bugs: E. coli (95%), Proteus, Klebsiella, Staphylococcus saprophyticus (frequent causes of Lower UTIs). Also enterococcus faecalis, staph epidermis.
Catheter associated UTIs is likely staph epidermis
UTI - Diagnosis
Clinical, Dipstick (nitrite, leucocytes +ve), Bloods - WBCs, Neutrophils, CRP,MSU MC&S (see organism, pyuria) – beware epithelial cells.
UTI - Rx
Cephalexin or nitrofurantoin
Nitrofurantoin is 1st line from NICE or Trimethoprim if low risk of resistance, but check EGFR is >45ml/min if giving Nitrofurantoin
If catheter associated - gentamicin/amikacin
Pyelonephritis - Rx
If pyelonephritis – Coamox +/- Gent OR Cefuroxime +/- Gent
Cystitis
inflammation of the bladder, often caused by infection
Uncomplicated vs Complicated UTI
Uncomplicated urinary tract infection refers to infection in a structurally and neurologically normal urinary tract.
Complicated urinary tract infection refers to infection in a urinary tract with functional or structural abnormalities (including indwelling catheters and calculi).Generally seen in:
- Men
- Pregnant women
- Children
- Patients who are hospitalised or in health care associated settings.
There are more likely to be caused by non–E.coli organisms
UTI - RFs
- Obstruction (intra or extra renal)
- Vesicoureteric reflux
- Haematogenous
Urine Microscopy - White Cells and Squamous Epithelial Cells
White cells Pyuria – indicative of infection
Squamous epithelial cells – indicative of contamination
Causes of Sterile Pyuria
Prior treatment with antibiotics Calculi Catheterisation Bladder neoplasm TB Sexually Transmitted Disease
Fungal UTI
Remove catheter
Don’t need to give medication
Hep A
- Acute hepatitis IP 2-6 weeks
- Often subclinical
- Faecal-oral spread
- Notifiable
- Occupational risks
- GUM clinics
- There is a vaccine
Hep B - General
- DNA Virus
- Sexual
- Vertical
- Blood products
- ACUTE and CHRONIC
- Chronic = 6 months or more
- Can lead to cirrhosis and HCC/liver failure
- Vaccine available
Chronic Hep B - Rx
Interferon alpha Lamivudine Tenofovir Entecavir Emtricitabine
Hep C- General
- RNA virus
- Flaviviridae
- Mainly blood product spread
- 60-80% chronicity
- Natural history
- Acute HepC: 20-40% of people clear, 60-80% chronically infected
Acute Hep C - Rx
Peginterferon alfa-2b Combination therapy (pegylated - not cleared as quickly)
Hep D
Can’t get D without B
Rx: INFa
Hep E
Like Hep A, but from Indochina, can be chronic and spread via pigs
Treatment: ribavirin
Vaccine - effective
Rare complications - CNS disease – Bell’s palsy, Guillain Barre, other neuropathy, Chronic infection
Infective Endocarditis - Duke’s Criteria
BE FEVER
Major - BE:
- Bacteraeima - >2 cultures, 12 hours apart.
- Echo findings - vegetations
Minor- FEVER:
- Fever of >38 degrees
- Echo findings that don’t meet the major criteria
- Vascular phenomenon e.g. embolization, stroke, PE
- Evidence of immune complex formation or microbiology not meeting major criteria
- Risk factors – murmur, IVDU
2 major, 1 major & 3 minor or 5 minor for diagnosis.
Infective Endocarditis - Presentation and RFs
Symptoms & Signs:
- FLAWS
- Chest Symptoms (SOB, tightness)
- Janeway lesions, osler’s nodes (painful), splinter haemorrhges, roth spots (eyes)
RFs:
- Rheumatic heart disease
- Congenital Heart disease
- IVDU
Subacute Infective Endocarditis
Takes weeks - months
Likely Strep Viridans
Acute Infective Endocarditis
Takes days - weeks
Likely Staph Aureus
Assoc with IVDU and therefore Tricuspid Valve involvement.
Other causes of IE
Gm –ve HACEK organisms
H - Heamophilius species A - aggregatibacter species C - cardiobacterium species E - eikenella corrodens K - kingella species
IE - Rx
Strep Viridans – BenPen & Gent
MSSA - Flucloxacillin
MRSA – Vancomycin +
Other
Prosthetic valve - Vanc & Gent & Rifampicin
