Infection / Med Micro Flashcards
Antibiotic Stewardship
What are the aims of AMS?
*LOB: Understand the aim of AMS as promotion of judicious use of antimicrobials for current patients and preserving antimicrobials for future patients
Antimicrobial Stewardship
Judicious Use: Ensure antimicrobials are used appropriately for the current patient, minimizing misuse (e.g., inappropriate prescriptions or overuse).
Preservation: Protect the effectiveness of antimicrobials for future patients by reducing the development of antimicrobial resistance (AMR).
AMS focuses on balancing effective treatment with resistance prevention for long-term efficacy
Antibiotic Stewardship
AMS categories
*LOB: Understand the aim of AMS as promotion of judicious use of antimicrobials for current patients and preserving antimicrobials for future patients
Firm Diagnosis (Pathogen Unclear): Start empiric antibiotics, adjust based on diagnostic tests (e.g., PCR, culture). Use broad-spectrum initially, but de-escalate once pathogen is identified
Febrile Illness of Unknown Cause: Many antimicrobials are given in this context, particularly in primary care. Accurate diagnostics (e.g., CRP, procalcitonin) are crucial to differentiate between bacterial, viral, or non-infective causes
Antibiotic Stewardship
Principles of Empirical Antimicrobial Use
*LOB: Explain the principles of giving empirical antimicrobials according to clinical syndrome - right drug, person, dose, route, time, duration
- Right Drug: Choose an antimicrobial based on the likely pathogen (e.g., Streptococcus pneumoniae for pneumonia) before definitive results. Consider drug’s ability to reach the infection site and minimize toxicity/resistance.
- Right Person: Account for patient-specific factors such as immune status, allergies, comorbidities (e.g., renal function).
- Right Dose: Use the correct dose to ensure adequate drug levels at the infection site without underdosing or overdosing.
- Right Route: Start IV if rapid action is needed, but switch to oral (PO) as soon as possible.
- Right Time: Start treatment within the first hour in emergencies (e.g., sepsis).
- Right Duration: Use the shortest effective duration to minimize exposure and resistance (e.g., 5-7 days for common infections, reassess at 48-72 hours)
Antibiotic Stewardship
Principles of Empirical Antimicrobial Use
*LOB: Explain the principles of giving empirical antimicrobials according to clinical syndrome - right drug, person, dose, route, time, duration
- Right Drug: Choose an antimicrobial based on the likely pathogen (e.g., Streptococcus pneumoniae for pneumonia) before definitive results. Consider drug’s ability to reach the infection site and minimize toxicity/resistance.
- Right Person: Account for patient-specific factors such as immune status, allergies, comorbidities (e.g., renal function).
- Right Dose: Use the correct dose to ensure adequate drug levels at the infection site without underdosing or overdosing.
- Right Route: Start IV if rapid action is needed, but switch to oral (PO) as soon as possible.
- Right Time: Start treatment within the first hour in emergencies (e.g., sepsis).
- Right Duration: Use the shortest effective duration to minimize exposure and resistance (e.g., 5-7 days for common infections, reassess at 48-72 hours)
Antibiotic Stewardship
Types of Microbiology/Virology Specimens:
*LOB: Know when and what microbiology/virology specimens to take and essential clinical details to write on laboratory requests
Types of Specimens:
Blood cultures for suspected sepsis or febrile conditions.
Urine cultures if UTI is suspected.
Sputum cultures for productive coughs (especially in pneumonia).
CSF if meningitis is suspected.
Respiratory viral swabs for viral infections (e.g., SARS-CoV-2, influenza).
Stool cultures if diarrhea is present, check for Clostridioides difficile if antibiotics were recently used.
Antibiotic Stewardship
Essential Clinical Details on Lab Requests:
*LOB: Know when and what microbiology/virology specimens to take and essential clinical details to write on laboratory requests
Include relevant travel history, presence of chronic lung diseases (e.g., bronchiectasis), immunocompromised status, ICU admission, etc. This ensures that the laboratory selects appropriate tests and interpretations
When to Take Specimens: Ideally before starting antibiotics to avoid skewing results, especially in conditions like sepsis, UTIs, respiratory infections, meningitis.
Antibiotic Stewardship
Local Guidelines for Abx
*LOB: Be aware of the need to access local guidelines for treating specific conditions
Importance: Use local or hospital-specific guidelines for empiric therapy, which take into account local resistance patterns and likely pathogens.
Tools: Microguide app or local hospital intranet can provide access to condition-specific guidelines, ensuring the most effective and safe treatment is chosen
Antibiotic Stewardship
Daily Review of Antimicrobials:
*LOB: Know and understand why antimicrobials should be reviewed daily according to clinical picture and laboratory/imaging results
Why: To ensure ongoing appropriateness of treatment based on updated clinical status and microbiological results.
Adjust therapy based on:
Clinical Picture: If the patient improves, consider de-escalation or stopping.
Lab/Imaging Results: Narrow spectrum where possible if results confirm specific pathogen sensitivity.
Consider switching from IV to oral (PO) as the patient stabilizes (following the C’MON mnemonic: Clinically stable, Markers improving, Oral route possible, No deep-seated infection).
Action: Stop antimicrobials if no infection is confirmed, change to a narrower agent, or continue with the shortest appropriate duration. Always aim to limit resistance development
Viral and Anti-Viral
RECAP: How do viruses replicate?
*LOB: Describe the diseases caused by members of the herpes virus family
Viral and Anti-Viral
How is Herpes categorised?
*LOB: Describe the diseases caused by members of the herpes virus family
Alpha HSV1,2, ZVZ
Beta CMV, HHV-6, HHV-7
Gamma EBV, HHV-8
Viral and Anti-Viral
What diseases do Alpha Herpes cause?
*LOB: Describe the diseases caused by members of the herpes virus family
HSV1,2 Herpes Labalis, Herpes Genitalis
VZV Chickenpox, Shingles
Viral and Anti-Viral
What diseases do Beta Herpes cause?
*LOB: Describe the diseases caused by members of the herpes virus family
CMV Mononucleosis like illness, retinitis, collitis, oesophagitis
HHV-6 Sixth disease, encephalitis
HHV-7 Exnathem Subitum
Viral and Anti-Viral
What diseases do Gamma Herpes cause?
*LOB: Describe the diseases caused by members of the herpes virus family
EBV Infectious mononucleosis, Burkitts Lymphoma, nasopharyngeal carcinoma
HHV-8 Kaposki’s Sarcoma, Multicentric Castlemanns disease
Viral and Anti-Viral
What is Herpes labialis
*LOB: Describe the diseases caused by members of the herpes virus family
Cold sores; caused by herpes simplex virus (HSV)
* Nearly always HSV-1
* Spread by direct contact with lesions
(asymptomatic shedding frequent)
* Primary infection: frequently asymptomatic,
may experience pharyngitis, fever, mouth
ulceration and lymphadenopathy
* Recurrence: very common, classically, prodromal
tingling followed by localised painful blisters that
resolve over 5 – 7 days
Viral and Anti-Viral
What is Herpes genitalis
*LOB: Describe the diseases caused by members of the herpes virus family
Genital herpes; caused by herpes simplex virus
(HSV)
* Classically HSV-2 but 50 – 80% HSV-1 in some
settings
* Primary infection: again frequently
asymptomatic, may experience painful
ulceration, fever, lymphadenopathy and urinary
retention
* Recurrence: localised ulceration; HSV-2 > HSV-1
Viral and Anti-Viral
Herpes simplex encephalitis
*LOB: Describe the diseases caused by members of the herpes virus family
Severe, life-threatening infection of the CNS
* Virus spreads via neurons to CNS
* Sporadic, no seasonal occurrence
* SIGNS: Fever, Fits, Funny behaviour
* Also: disturbed conscious level, focal
neurology
* Distinct clinical syndrome from meningitis:
headache, photophobia, meningism +/- fever
Viral and Anti-Viral
Chicken Pox
*LOB: Describe the symptoms and signs, and treatment of chickenpox and shingles
Caused by primary infection with varicella-zoster virus
(VZV)
* Sporadic with a spring-summer peak in UK
* HIGHLY infectious via respiratory droplets and
shedding from lesions
* Infectious from 1-2 days before rash onset until all
lesions crusted over (usually 5-7 days)
* Generally uncomplicated in healthy children
* Adults at risk of more severe disease and pneumonitis
* Immunocompromised can experience disseminated
infection
Viral and Anti-Viral
Shingles
*LOB: Describe the symptoms and signs, and treatment of chickenpox and shingles
Viral and Anti-Viral
Treatment of HSV and VZV
*LOB: Describe the symptoms and signs, and treatment of chickenpox and shingles
Virally-encoded enzymes are key targets: thymidine kinase and DNA polymerase
– Aciclovir (ACV, aciclovir, prototype drug)
– Valaciclovir (vACV prodrug of aciclovir, high bioavailability)
– Famciclovir (prodrug of penciclovir, high bioavailability)
- Oral doses generally well-tolerated, bioavailability of
ACV 15-30%, t½ = 3 hrs, renally-excreted - Poorly soluble in urine so crystallisation of drug in
tubules can occur at high IV doses and in renal failure - Chronic use has not been associated with toxic effects
Viral and Anti-Viral
Treatment of HSV and VZV
*LOB: Describe the symptoms and signs, and treatment of chickenpox and shingles
Virally-encoded enzymes are key targets: thymidine kinase and DNA polymerase
– Aciclovir (ACV, aciclovir, prototype drug)
– Valaciclovir (vACV prodrug of aciclovir, high bioavailability)
– Famciclovir (prodrug of penciclovir, high bioavailability)
- Oral doses generally well-tolerated, bioavailability of
ACV 15-30%, t½ = 3 hrs, renally-excreted - Poorly soluble in urine so crystallisation of drug in
tubules can occur at high IV doses and in renal failure - Chronic use has not been associated with toxic effects
Viral and Anti-Viral
Mode of Action of Acyclovir
*LOB: Describe the symptoms and signs, and treatment of chickenpox and shingles
Monophosphorylated by viral thymidine kinase (TK)
and then further phosphorylation by cellular kinases to
Affinity of cellular kinases for ACV is poor but activity of these enzymes in virally-infected cells is greatly increased
Affinity of cellular DNA polymerase for ACV-PPP 10- to 30- fold lower than herpesvirus DNA polymerase
Hence inhibition of DNA synthesis by aciclovir in herpesvirus-infected cells is much greater
Susceptibility: HSV-1 > HSV-2»_space; VZV; susceptibility of other herpesviruses is negligible
VZV TK 10x less sensitive so higher doses required
Viral and Anti-virals
How do CMV and EBV drugs work?
*LOB: Understand the importance and principles of diagnosis and treatment of viral infections in the immunocompromised including EBV and CMV
Ganciclovir (GCV) IV and valganciclovir (vGCV, oral pro-drug)
are effective
* Longer intracellular t½ (18 hrs)
* Major drawback is toxicity: marrow suppression (neutropenia
and thrombocytopenia)
* Foscarnet (FOS) – analogue of pyrophosphate, IV only
* Major side effects are renal impairment and electrolyte
disturbance
* Cidofovir (CDV) – nucleoside analogue, broad activity against
DNA viruses, IV or topical
* IV given weekly, nephrotoxic++ and contraindicated in renal
impairment
* Requires prior IV hydration and co-treatment with probenecid
* All 3 also effective against HSV, VZV, EBV, and HHV-6
Viral and Anti-virals
When to treat CMV?
*LOB: Understand the importance and principles of diagnosis and treatment of viral infections in the immunocompromised including EBV and CMV
Universal prophylaxis: GCV for all transplant recipients
* Pre-emptive therapy: treat viraemia without evidence of
end-organ disease (EOD)
* Some controversy about which strategy is best
* End-organ disease: consider treatment
Viral and Anti-virals
When to treat CMV?
*LOB: Understand the importance and principles of diagnosis and treatment of viral infections in the immunocompromised including EBV and CMV
Universal prophylaxis: GCV for all transplant recipients
* Pre-emptive therapy: treat viraemia without evidence of
end-organ disease (EOD)
* Some controversy about which strategy is best
* End-organ disease: consider treatment
Viral and Anti-virals
What is Respiratory transmission
*LOB: Understand the importance, clinical presentations, and management of respiratory viral infections including influenza and SARS-CoV-2
Viral and Anti-virals
Influenza A
*LOB: Understand the importance, clinical presentations, and management of respiratory viral infections including influenza and SARS-CoV-2
Viral and Anti-virals
Neuraminidase inhibitors
*LOB: Understand the importance, clinical presentations, and management of respiratory viral infections including influenza and SARS-CoV-2
Oseltamivir (oral), zanamivir (dry powder inhaler)
- IV and nebulised zanamivir can be obtained
- Effective for influenza A and influenza B
Indicated if all 3 apply (NICE guidance):
1. National surveillance indicates
influenza is circulating
2. Patient is in a ‘risk-group’
3. Within 48 hours of symptom
onset (36 hours for zanamivir
Viral and Anti-virals
SARS-CoV2 Treatment Guidance
*LOB: Understand the importance, clinical presentations, and management of respiratory viral infections including influenza and SARS-CoV-2
Investigation of Infection
UTI signs and symptoms
*LOB: Describe symptoms and signs of patient with infection
Investigation of Infection
Different staining
*LOB: List key principles in diagnosis of common bacterial infections
Investigation of Infection
Blood Cultures
*LOB: Describe how blood cultures are taken, processed and interpreted
bacteria or fungi in the blood, which can indicate bloodstream infections like sepsis, bacteremia, or fungemia
Processing of Blood Cultures
Incubation
Bottles are placed in a blood culture incubator that continuously monitors for growth by detecting CO2 production from the metabolism of microorganisms.
The bottles are incubated for 5-7 days, but results may be flagged earlier if growth is detected.
Detection of Growth:
If the system detects microbial growth, an alert is sent to the laboratory.
A Gram stain of the culture bottle content is performed immediately to provide a preliminary identification (e.g., Gram-positive cocci, Gram-negative rods).
Subculture and Identification:
The positive culture is subcultured onto solid agar plates to allow the bacteria to grow in isolation.
Identification tests (e.g., biochemical testing, MALDI-TOF, PCR, or genomic sequencing) are done to determine the exact organism.
Antimicrobial Sensitivity Testing (AST):
Once the organism is identified, the lab performs susceptibility testing to determine which antibiotics are effective.
Results are reported as susceptible, intermediate, or resistant to specific antibiotics.
Investigation of Infection
Range of tests & microbes
*LOB: Describe how blood cultures are taken, processed and interpreted
Investigation of Infection
Abscess
*LOB: Define PUO, list common causes & key investigations
Investigation of Infection
Clostridium difficile infection
*LOB: Define PUO, list common causes & key investigations
Investigation of Infection
*LOB: Differentiate between bacteraemia, septicaemia & sepsis syndrome
BacteraemiaThe presence of bacteria in the bloodstream, typically transient or asymptomatic
Septicaemia (outdated term)Previously used to describe the presence of bacteria in the blood (bacteraemia) with accompanying clinical signs of systemic infection. It is now largely replaced by the term sepsis.
SepsisA life-threatening organ dysfunction caused by a dysregulated immune response to infection. It represents a severe systemic infection with widespread inflammation affecting multiple organs.
