Academic Day Seminar #10: Infectious Diseases

E.g. aInfectious Diseases:

I have just started my General Medicine rotation, so I anticipate that this session will come in very useful for my current and future rotations! 🙂

  • For each site, familiarize yourself with the institution-specific antibiogram (periodic summaries of antimicrobial susceptibility of local microbial isolates)
    • Limitations of antibiograms: Only summarizes susceptibility (does not provide information on the context (e.g. is patient sick?), patient in which the bacteria was isolated), only includes one isolate per patient (not representative of all the different isolates in hospital)

Resources:

Microbiology and Laboratory Testing:

  • Specimen Assessment: the key for accurate identification of microbial pathogens is properly collected specimens
  • Consider:
    • Why was the specimen collected?
      • E.g. smelly urine can be thought to be indicative of infection…but if patient is otherwise asymptomatic, was it necessary?
    • How the specimen was collected (catheter vs midstream urine sample)?
      • E.g. was it something from a dirty foley catheter sitting in a patient for several days (will be colonized with various pathogens)? The urine sample may be from the patient’s bladder or possibly washed from the foley catheter. With a midstream urine sample would be less concerned with contaminiation
        • If you have a high suspicion of infection in this case (e.g. fever, increased WBC), one approach is to have the nurse change the foley and get a clean catch sample
    • When was the specimen collected?
      Whether the patient was receiving antimicrobials at the time of specimen collection

      • If have negative result, may be masked by the fact that the patient received meropenem a few days ago…might not be indicative that patient does not have an infection
  • Once a sample is sent to microbiology, it will undergo assessment via various means:
    Microscopy, C&S, Antigen testing, Nucleic acid tests, Serology
  • Microscopy (looking down a microscope):
    • Presence of PMNs (inflammatory cells – would suggest inflammatory response to what might be there), other cells (e.g. epithelials)
      • E.g. if no PMN, are they neutropenic? Is there no response to what is growing?
      • E.g. if expectorate sputum from mouth, sample will be contaminated with what is in the mouth — and the # of epithelial cells helps to suggest that the bacteria grown may be from spit
    • Stains – helps to differentiate between organisms
      • E.g. gram stains, acid-fast (e.g. tuberculosis or other mycobacterium), India link (for fungal organisms)
      • Show presence of PMNs, RBCs, epithelial cells and predominant organisms
    • Morphology – of organism:Cocci vs bacilli vs coccobacilli
    • Configuration: pairs vs chains vs clusters
    • Helps to give “hints” while waiting for cultures
      • S. aureus: gram + cocci in clusters (golden grapes)
      • S. pneumoniae: gram + cocci in pairs
  •  C&S: help identify microorganisms
    • MacConkey agar: Lactose fermenting vs non-fermenters
    • Blood agar: alpha, beta, gamma hemolysis with Streptococci
    • Biochemical tests are also used to help differentiate bacteria
      •  Examples
        • Catalase: differentiates Staphylococci from Streptococci
        • Coagulase: differentiates S. aureus from other Staphylococci
        • Oxidase: differentiates Pseudomonas spp, Burkholderia from Acinetobacter, Strentrophomonas
        • Lactose fermentation:
    •  Antimicrobial susceptibility is based on the MIC, and interpretation is outlined by Clinical and Laboratory Standards Insitute (CLSI)
      • S/I/R: relates to the achievement of concentrations with typical drug dosing in relation to the specific MICs
      • Minimum Inhibitory Concentration (MIC): lowest antimicrobial concentration that inhibits visible growth. Clinically used to guide antimicrobial choice and dosing.
        • Can’t compare MICs together – doesn’t relate to susceptibility and CLSI will tell us the S/I/R tell us susceptibility
          • E.g. can’t say penicillin with a lower MIC vs. cephalosporin with a higher MIC — that penicillin is more susceptible since different drug groups
        • Examples of when we ask for MIC:
          • Viridans group Streptococci IE (MIC is used to determine penicillin dose and duration of therapy)
          • MRSA (Higher vancomycin MICs associated with treatment failure)
        • How do they calculate MICs?:
          • tiny wells of different drug concentrations and different drugs and machines will read it with light technology and chemical reactions – all automated – more quantitative tests of MICs
          • E-test and KB test: qualitative tests of MICs
            • What is the issue with this?: interpretation is subjective
        • Limitations of MIC:
          • E.g. why might someone be responding to a drug that shows resistance, or vice versa?
          • It is a static concentration of the drug in-vitro — in your body, the drug concentrations are fluctuating or may concentrate  + immune system is helping defeat the pathogens
          • In the body, the innocum of the pathogens might be too high…making it harder for the drug
    • + Microbiology results do not always indicate the presence of infection!!!
      • Consider:
        • How the culture was obtained (e.g. catheter vs. midstrain urine; superificial wound swab vs surgical biopsy)
        • Context in which culture was taken (septic patient vs. patient with new onset confusion)
        • whether patient was receiving antimicrobials at time of culture sampling
    • Ancillary Tests:
      • Antigen tests: of variable sensitivity, should consult with ID or medical microbiology – e.g. cryptococcal antigen
      • Nucleic acid tests: PCR based tests used to identify various micro-organisms
        • Useful e.g. when patient is given pip-tazo → can use this test to go “fishing” as to what could have caused the infection
      • Serology: often used to identify organisms that are difficult to grow via culture  (useful if can’t identify with gram stain)

Microbiology results interpretation, consider:

  • Where is the organism isolated? Non-sterile vs sterile site?
  • What is the organism? Is it considered part of normal flora? Organism associated with causing infection?
  • Is the isolated organism the only pathogen involved? Source?
    • Where is this organism usually found (environmental vs normal)
    • How the organism ended up in the specimen that was sent for culture
  • Is a negative culture truly negative?
  • Patient factors (i.e. immune status, burns, hardware)
  • Patient’s clinical status

When to call the microbiologist:

  • Excellent resources of the microbiology and infectious diseases issues
  • Consider calling the medical microbiologist when:
    • additional susceptibilities or MICs are required
    • further identification/speciation of an isolate is required (i.e. yeast (not C. albicans) – if need to treat that yeast, ask if can specify which)
    • guidance needed on interpretation of a result
    • guidance needed on microbiology testing
    • guidance needed on antimicrobial therapy
  • Best to contact early as will throw out information over time

Antimicrobial PK/PD:

  • In-vitro susceptibility studies, such as time-kill curves, help to delineatie antimicrobial activity characteristics
    • Bacteriocidal vs. Bacteriostatic
      • Bacteriostatic: inhibits growth but requires a much higher concentration to kill (e.g. clindamycin, tetracyclines, macrolides, linezolid)
        • Minimum bacteriocidal concentration (MBC) >> MIC
        • Requires intact immune system (relying on the immune system to mop up the rest of the infection)
      • Bacteriocidal: able to kill organisms at similar concentrations to those that inhibit their growth (e.g. beta-lactams, fluoroquinolones)
        • MBC ~ MIC
        • Preferred for serious infecions, especially in the immunosuppressed
      • No great studies that compare them head-to-head clinically
    • Time-dependent vs. Concentration-Dependent
      • Time-dependent: antimicrobials display some increased activity with increased concentrations but plateaus at about 4-5 times the MIC
        • Antimicrobial activity is dependent on duration of exposure to drug to pathogen
        • PK/PD parameters: t >MIC, AUC/MIC
        • Examples: Beta-lactams, vancomycin
        • Most antimicrobials are time-dependent
      • Concentration-dependent: antimicrobials display increased antimicrobial activity with increasing peak concentrations
        • PK/PD parameters: Cpeak/MIC
        • Examples: fluoroquinolones, aminoglycosides, daptomycin, rifampin, metronidazole
      • How can we apply this into our drug dosing?
        • Concentration-dependent: Extended interval aminoglycosides
        • Time-dependent: especially with pathogens that have increased resistance = continuous infusions of beta-lactams (important to maintain a certain concentration above the MICs for a certain period of time – for Beta-lactam this is 40-60% of the time)
    • Post-antibiotic effect: where bacterial growth continues to be suppressed even with undetectable antimicrobial concentrations
      • Thought to be due to various factors such as host immune response
      • Extent of post-antibiotic effect depends on the antimicrobial bacteria combination
      • E.g. aminoglycoside have prolonged post-ab effect vs. G – bacteria

Approach to the Infectious Diseases Patient:

Information Gathering:

  • ID, CC, HPI (including previous antimicrobial tx (drug, duration, efficacy), PMHx (including history of previous infections – i.e. MRSA, C diff, immune status), Medication Hx, Allergies, Social Hx, Vaccination status
  • Exposures (as appropriate): close contacts/sick contacts, dietary (e.g. raw foods), anmials, travel history (recent, current or past), environmental, occupational
  • Comprehensive ROS: head to toe (e.g. DERM – pressure ulcers, LYMPH) – Foreign bodies: prosthetic joints, valves, IV catheters, foley catheters, pace-makers
  • Test results: Laboratory, Micrbiology and Radiology results

Checklist:

  • Does my patient have an infection?
  • What is the likely souce of infection?
  • If diagnosis or etiology of infection not clear, can antimicrobials be delayed until diagnostic tests are performed?
  • If treatment required, what is the expected microbiology? Empiric antimicrobial therapy options?
  • Source control?
  • Reserve risk factors for ongoing/recurrent infection?
  • Adjust/narrow/stop antimicrobials?

Does my patient have an infection? If so, how long do we keep the patients on antibiotics?

  • Consider non-specific findings:
    • vitals
      • Temp (36.5-37.5) → Fever > 38.3
      • BP <120/80 mmHg
      • HR 60-100 bpm
      • RR 12-18 bpm
    • symptoms (chills, rigors, fatigue, confusion, poor appetite)
    • lab (WBC, CRP)
  • Consider localizing signs/symptoms (hint as to the source if have pain/erythema at site of infection, and radiographic evidence of infection)
  • Microbiologicl testing results

Systemic Inflammatory Response Syndrome (SIRS)

  • Not specific to infection! Non-specific clinical response to inflammation of non-infectious or infectious etiology
  • 2 or more of:
    • Temp > 38 or <36
    • WBC > 12 or < 4 or > 10% immature (band forms)
    • HR > 90
    • RR >20 or PaCO2 <32mmHg

Fever is not always from infection (e.g. patients can present hypothermic – and that’s their sign of infection) → consider the whole patient picture

  • Also consider non-infectious causes of fever (e.g. inflammation, post-operative (usually febrile the 1st 24 hours after), malignancies, drugs (e.g. allergic rxn to drug), DVTs)

WBCs: Leukocytosis (WBC >11 x 10^9) is a normal response to infection or inflammation

  • Not specific to infection – e.g. inflammation, stresses, etc.
    • Drug causes (e.g. corticosteroid, lithium)
    • Trauma
    • Hemolytic anemia
    • Leukemias
    • Myeloproliferative disorders
  • Absolute WBC count composes of:
    • granulocytes
      • neutrophils (polymorphonuclear granuocytes or PMNs)
      • Eosinophils: increase in allergic reactions or parasitic infections
      • Basophils
    • Monocytes
    • Lymphocytes: increase in viral infections, chronic infections, malignancies
  • Left-shift: mature circulating neutrohils (segs) move to site of infection, followed by release of immature neutrophils (bands) from bone marrow → increased ratio of immature to mature neutrophils (“left-shift”)
  • Abnormal WBC response (e.g. leukopenia) is also observed in response to infections in:
    • Neutropenic/immunosppressed patients
    • Severe sepsis
    • Elderly

Acute Phase Reactants: Non-specific markers of inflmmation

  • CRP
  • ESR
  • Platelets
  • Ferritin

Determine if organisms seen on culture are pathogens, colonizers or contaminants

  • Pathogens: organism causing damage to host tissue and elicit host response
  • Colonizers: organisms that make up normal flora or exist at the host site without eliciting host response
  • Contaminant: organisms that comprise normal flora that are isolated from sterile sites (e.g. S. epidermidis in blood)
  • Consider all patient factors and likelihood of organism to cause infection!

Can antimicrobials be delayed?

  • If unwell, septic or unstable with infection→ do NOT delay
  • If clinically stable, diagnosis/etiology of infection is not clear → somtimes held in order to improve yield of more invasive cultures (e.g. bone biopsy for OM)

Summary of considerations:

Consider Patient Factors:

  • Acuity of illness, Allergies, Previous antimicrobial use, Organ function, PO intake, weight, Drug interactions
  • Age
  • Allergies/Intolerances
  • Comorbidities (i.e. immune function)
  • Risk factors
    • e.g. diabetes control in diabetic foot infection
    • e.g. immunizations
  • Concomitant medications/drug interactions
  • Renal function
  • Hepatic function
  • Genetic susceptibility to adverse effects
  • Pregnancy
  • History of antimicrobial use
  • Adherence
  • Social history

Consider bug factors:

  • MSSA – beta-lactams (e.g. cloxacillin) work better against this than vancomycin
  • Pulmonary surfactant interacts with daptomycin
  • Likelihood of acquired resistance
    • ESBL amongst enterobacteraciae
    • Amp C mediated B-lactamase production against SPICE/SPACE organisms

Consider drug factors:

  • PK/PD factors (e.g. required drug concentrations)
  • Activity/ability to penetrate the site of infection
  • Bacteriostatic vs bacteriocidal activity
  • Development of resistance
  • SEs profile
  • Route of administration
  • Frequency of administration
  • Availability Cost

Source control:

  • Drainage of abscesses
  • Debridement of infected tissue
  • Removal of infected devices or foreign bodies
  • Correct of anatomic derangements contributing to infection

Application into  my practice!:

  • Reassess antimicrobial therapy regularly to avoid prolonged, unnecessary broad spectrum antimicrobial and to assess for step down to PO (if on IV)
  • Treat the patient; not the cultures!

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