Micro - Management, Hepatitis Serology, CNS Infections and Congenital/Childhood Infections Flashcards
ABX inhibiting cell wall synthesis
BCG
Beta lactams - penicillin, cephalosporins
Carbapenems (these are also B lactams) - meropenem
Glycopeptides - vancomycin, teicoplanin
ABX inhibiting protein synthesis
TAM
Tetracyclines - tetracycline, doxycycline
Aminoglycosides - gentamycin
Macrolies - erythromycin, clarithromycin
ABX inhibiting nucleic acid synthesis
Quinolones - ciprofloxacin, ofloxacin
Other - metronidazole, trimethoprim, rifampicin
ABX inhibiting folate synthesis
Sulphonamides - trimethoprim?, septrin
Diaminopyrimidines - trimethoprim
Amoxicillin
Beta-Lactams: Penicillins (-cillin)
Cover Gram +ve mainly
Broad-spectrum, covers some Gram –ve (like Haemophilus, enterococci) –> first-line for pneumonia
broken down by β-lactamase produced by S. aureus and many Gram negative organisms
Piperacillin
Beta-Lactams: Penicillins (-cillin)
Cover Gram +ve mainly
Broad-spectrum, covers some Gram –ve (like Haemophilus) –> first-line for pneumonia. COVERS PSEUDOMONAS and other non-enteric gram -ves
broken down by β-lactamase produced by S. aureus and many Gram negative organisms
Ampicillin
Beta-Lactams: Penicillins (-cillin)
Cover Gram +ve mainly
Listeria listeria
Flucloxacillin
Beta-Lactams: Penicillins (-cillin)
Cover Gram +ve mainly
Staph aureus (skin infections)
Less active than penicillin but stable to B-lactamase produced by staph a
Benzylpenicillin
Beta-Lactams: Penicillins (-cillin)
Cover Gram +ve mainly
Group A strep (“sore throat”
Penicillis are often used with
beta-lactamase inhibitors:
Co-amoxiclav = amoxicillin + clavulanic acid
Tazocin = piperacillin + tazobactam
Protect penicillins from enzymatic breakdown and increase coverage to include S. aureus, Gram negatives and anaerobes. V useful for HAI.
What to use if someone is penicillin allergic
Just rash: use cephalosporin (5-10% cross-reactivity)
Anaphylaxis: doxycycline for pneumonia, erythromycin for impetigo
1st Generation Cephalosporins (Beta-Lactams)
(cefalexin): Gram +ve but not –ve
Cefuroxime is 2nd gen
3rd generation Cephalosporins (Beta-Lactams)
(cefotaxime, ceftriaxone, ceftazidime): Gram –ve but not +ve
Used in hospital acquired pneumonia
Cephalosporin management of pseudomonas
Ceftazidime
Cephalosporin management of meningitis
IV ceftriazone
Carbapenems - uses
For severe infections, when beta-lactams would not work
Extended-Spectrum Beta-Lactamases = resistant to beta-lactams
Carbapenemase enzymes becoming more widespread. Multi drug resistant Acinetobacter and Klebsiella species.
Meropenem
Sepsis of unknown origin, severe abdominal infections
Glycopeptides
Gram +ve only
MRSA = vancomycin (IV only)
Oral vancomycin can be used to treat serious C. difficile infection
Slowly bactericidal
Nephrotoxic – hence important to monitor drug levels to prevent accumulation
Aminoglycosides (end in –cin)
- Rapid, concentration-dependent bactericidal action
- Require specific transport mechanisms to enter cells
- Ototoxic & nephrotoxic, therefore must monitor levels
- Synergistic combination with B-lactams
- No activity vs. anaerobes
Gram -ve only
Pseudomonas = gentamycin, tobramycin
Tetracycline (end in –cycline)
- Broad-spectrum agents with activity against intracellular pathogens (e.g. chlamydiae, rickettsiae & mycoplasmas) as well as most conventional bacteria
- Bacteriostatic (stops reproduction)
- Widespread resistance limits usefulness to certain defined situations
- Do not give to children or pregnant women
- Main side-effect: Light-sensitive rash
Intracellular bacteria
Chlamydia = doxycycline
Macrolides (end in –mycin)
Bacteriostatic
Gram +ve –> substitute for penicillin if allergic (vs staph/strep).
Also active against Campylobacter sp and Legionella. Pneumophila
Atypical pneumonia = add clarithromycin to amoxicillin
Oxazolidinones (end in –zolid)
Excellent for Gram +ve (not active against most -ve)
Vancomycin-Resistant Enterococci (VRE) = linezolid
Is expensive, may cause thrombocytopoenia and should be used only with consultant Micro/ID approval. Can cause optic neuritis –> don’t tend to use over long periods (more than 4 weeks).
Nitroimidazole (end in –azole)
Anaerobic bacteria
C. Diff = metronidazole
Under anaerobic conditions, an active intermediate is produced which causes DNA strand breakage
Rapidly bactericidal
Active against anaerobic bacteria and protozoa (e.g. Giardia)
Nitrofurans are related compounds: nitrofurantoin is useful for treating simple UTIs
Rx - herpes simplex & HSV encephalitis
HSV:
Aciclovir
2nd line = foscarnet
HSV encephalitis:
On clinical suspicion- Start empiric treatment immediately without waiting for test results
iv ACV 10mg/kg tds
If confirmed, treat for 14 - 21 days
Rx - varicella zoster
Acyclovir
Indications for Rx:
- Chickenpox in adults (risk of complication: pneumonitis)
- Zoster in adults >50 (risk of complication: post-herpetic neuralgia)
- 1o infection or reactivation in the immunocompromised
- Neonatal chickenpox
- If there is an increased risk of complications
Rx - cytomegalovirus (CMV) = immunocompromised
Ganciclovir (IV or vGCV = oral prodrug) Guanosine analogue - inhibits viral DNA synthesis.
Primary infection:
- Latency in blood monocytes and dendritic cells
- Reactivation (eg following immunosuppression)
Asymptomatic shedding in saliva, urine, semen and cervical secretions.
MAJOR pathogen in the immunocompromised (including solid organ and bone marrow transplant patients) – causes marrow suppression, retinitis, pneumonitis, hepatitis, colitis, encephalitis…
Can give:
Ganciclovir(GCV) iv. SEs: bone marrow, renal and hepatic toxicity. Contraindicated in BM suppression (neutropenia).
Valganciclovir (VGC) po
Foscarnet (FOS) iv / intravitreal - Non-competitive inhibitor of viral DNA, polymerase. Use when GCV contraindicated ie neutropenic patients (eg pre-engraftment post-BMT); GCV-resistant CMV; CMV retinitis (intravitreal implants). Nephrotixic.
Cidofovir (CDV) iv - Nucleotide (cytidine) analogue (Competitive inhibitor of viral DNA synthesis). Nephrotoxic - Require hydration + probenicid.
Also maribavir (inhibits viral kinase (UL97), effective in vitro against GCV resistant CMV), letermovir (CMV DNA terminase* inhibitor) - CMV prophylaxis in CMV+ SCT recipients. Give Ganiciclovir with IVIG for CMV pneumonitis
Rx - EBV (infectious mononucleosis, infects B cells- life-long)
Rituximab (anti-CD20) for post-transplant lymphoproliferative disease (reactivation of EBV with immunosuppression)
Rx - Influenza (A&B)
Oseltamivir (“Tamiflu”)
Neuraminidase inhibitor
Inpatients:
Indicated for all patients admitted to hospital due to influenza virus-related respiratory disease
Indicated in the community if all 3 apply (NICE guidance):
- National surveillance indicates influenza is circulating
- Patient is in a ‘risk-group’ *
- Within 48 hours of symptom onset (36 hours for zanamivir)
Peramivir - Neuraminidase inhibitor licensed in US, but also available in UK. H275Y mutation confers reduced susceptibility –> avoid use with oseltamivir resistance
Baloxavir merboxil
Rx - Respiratory Syncytial Virus (RSV) = in young kids
Treat: ribavirin (Guanosine analogue, PO)
Prevent: palivizumab
Rx - Adenovirus = after bone-marrow transplant
Cidofovir
Herd immunity threshold calculation
Herd Immunity threshold = 1 – 1/R0
R0= the average number of people that one sick person will infect. To eliminate a disease the effective R0 needs to be <1.
Herd immunity threshold = percentage of fully immune individuals required to stop the spread of disease.
Live attenuated vaccine
Stimulates all aspects of the immune system e.g. MMR, yellow fever
T cell response important in destroying infected cells.
Advantages:
Single dose often sufficient to induce long-lasting immunity
May stimulate response to multiple protective antigens
Strong immune response evoked
Local and systemic immunity produced – particularly important for infections where CMI plays an important role. Activation of all components of immune system
Disadvantages
Potential to revert to virulence
Can cause illness directly
Contraindicated in immunosuppressed patients
Interference by viruses or vaccines and passive antibody
Poor stability
Potential for contamination
Inactivated vaccine
Need adjuvant to boost immune response e.g. influenza, polio
Whole microorganism destroyed by heat, chemicals, radiation or antibiotics (e.g. Influenza, cholera, polio)
Advantages:
Stable
Constituents clearly defined
Unable to cause the infection
Disadvantages: Need several doses Local reactions commn Adjuvant needed Shorter lasting immunity
Subunit vaccine
Need adjuvant to boost immune response e.g. Hep B, HPV
Protein component of the microorganisms or synthetic virus like particles.
Lacking viral genetic material and unable to replicate.
Viral vector vaccine
Type of cloning –> grow viral proteins which induce immune response
DNA vaccine
Type of cloning –> inject genes encoding viral antigens –> host cells make the antigens (and therefore induce B and T cells)
Virus-like particles vaccine
Type of cloning –> virus which doe snot replicate (so you can give the intact virus)
Toxoid vaccine
Inactivated toxin e.g. tetanus, diptheria
Conjugate vaccine
Poorly immunogenic antigens and highly immunogenic adjuvant e.g. haemophilius influenza type B
Heterotypic vaccine
Pathogens which do not cause disease in humans e.g. BCG
Hep A Features
Faecal-oral
Acute, never chronic
“Fever, malaise, raised ALT in someone coming from India”
Hep B Features
DNA virus, same transmission modes as HIV (more likely sex than C)
Presents like Hep A, but can cause liver cancer and cirrhosis
Treatment: interferon-a and tenofovir
Hep C Features
RNA virus, same transmission modes as HIV (more likely blood than B) (“transfusion long time ago”)
80% become chronic –> 25% cirrhosis
PCR shows HCV RNA = acute; anti-HCV antibodies = chronic
Treatment: antiviral combination
Hep D Features
Need Hep B to get Hep D!
Treatment: interferon-a