medical microbiology

• Superficial mycoses: limited to outer surface or hair shafts, skin shafts and nails  

  Cutaneous mycoses: common fungal infection – deeper into epidermis – invasive hair and nail diseases. 

  Subcutaneous mycoses – caused by saprophytic fungi – unable to penetrate skin – introduced to body by puncture wound that’s been contaminated with soil.  
• Nodules > become ulcer > protrude out skin > pus containing drainage 
• Systemic mycoses: primary pathogens – introduced to lungs through breathing – spread to many organ systems. 
• Opportunistic mycoses – infections of patients with immune deficiencies (same principle of latent TB) 

   
• Characteristics of fungi: 

  • Most are obligate or facultative aerobes 
  • Digest food externally  

  Divided into 3 groups: 

  • Multicellular filamentous moulds 
  • Macroscopic filamentous fungi – mushrooms  
  • Single celled microscopic yeast 

   
• Fungal structure:  

  • Most cell walls are made of polysaccharides, lipid- phosphate – protein, protases and melanin 
  • Chitin is polysaccharide – long chain of n- acetylglucosamine 
  • Contain membrane-bound nucleus where DNA is wrapped round histone proteins 

   
• Pathogenesis: 

  • Most saprophytic or parasitic to plants – adapted to natural environment   
  • Other fungi have adapted to human environment  
  • Infection for humans is by chance event – if immune system has failed
• Virulence: 

  • Infection depends on inoculum size + immunity of host  
  • Ability to adhere to host cells  
  • Produce capsules to avoid phagocytosis  
  • Acquire iron from blood  
  • Damage host cells – secreting enzymes 

   
• Moulds: 

  • Made up of hyphae 
  • Hyphae grow at tip then divide and intertwine to form network called mycelium  
  • Digestive enzymes secreted from hyphal tip  
  • Stachybotrys (black mould) 
• Morphology: 

  • Hyphae – basic element of filamentous fungi  
  • Mycelium – web or mat structure  
• Impact on humans: 

  • Mild or severe symptoms  
  • Congestion, coughing, wheezing, sore eyes, skin irritation, headaches  
  • Some release mycotoxins – absorbed by skin or breathed in  
  • Long term exposure to toxins cause pulmonary fibrosis, cancers and kidney damage 
• Mushrooms/toadstools: 

  • Grow by producing mycelium below ground 
  • Produce visible fruiting bodies, holds spores 
  • Fruiting is made of hyphae which divide to produce diff parts of mushroom  
  • Gills underneath cap covered with spores – 10cm cap ca prod 100 million spores  
• Yeast: 

  • Small  
  • Facultative anaerobes  
  • Reproduce asexually or sexually  
  • Asexual reproduction is through budding or binary fission  
  • Yeast cells can form chains to to resemble hyphae  
  • Yeasts used in bread + alcohol 
  • Used model organism for genetic studies  
  • Are opportunistic pathogens  
  • Yeast cells resemble bacterial colonies  
  • Can be identified by ability to assimilate and ferment various carbon sources – utilize nitrate. 
• Dimorphic fungi: 

  • Exhibit filamentous mycelial morphology  when grown room temp – have typical yeast morphology – inside body and lab  
• Diagnosis: 

  • Culture 
  • Germ tube test  
  • Urease test 
  • Chromagar 
  • Dermatophyte medium  
  • Whole genome sequencing  

  Treatment: 

  • Polyenes – amphotericin B – bind directly to ergosterol in fungal cell membrane causing leakage and cell death  
  • Can also bind to cholesterol – needs to be titrated  
  • Toxic at higher concentrations  
  • Very effective topically  
• Echinocandins: 

  • Act through inhibition of D-glucan 
  • Non- toxic  
  • Limited application – due to large size  

  Azoles: 

  • Antifungal usually fungistatic  
  • Inhibit lanosterol demethylase enzyme  
  • Completely absorbed in GI  
  • Secreted in high levels of saliva  

  Allylamines: 

  • Inhibit ergosterol biosynthesis at the level of squalene epoxidase 
• Candida: 

  Superficial infections: athletes foot, jock itch  

  Mucosal infections: genital candidiasis, ocular candidiasis, oropharyngeal  

  Systemic: blood stream infection, sepsis, meningitis 
• Candida species: 

  • Belongs to phylum Ascomycota 
  • Diploid yeast cells – 4-6  
  • Multiply by budding 
• C.glabrata: 

  • 1 of the smallest species  
  • Major cause of candidemia + candidiasis 
  • Can live as mucosal commensal 
• C.parapsilosis; 

  • Produce both yeast and pseudohyphae in culture 

  C. krusei • Can grow as a yeast & pseudohyphae • Associated with candidaemia • Niche – natural sources e.g soil  
• C. parapsilosis • Frequently encountered in cancer patients, can cause candidemia • Can grow as yeast & can produce pseudohyphae  
• C. albicans • The most widespread yeast • Normal flora of oral cavity, genitalia, large intestine or skin in 20% of humans • Infections can be short--lived, superficial skin irritations to overwhelming fatal systemic diseases • Account for 80% of nosocomial fungal infections and 30% of deaths from nosocomial infections • Can produce pseudohyphae, true hyphae or yeast forms 
• Risk factors: 

  • Obesity, pregnancy  
  • Immune compromised  
  • Metabolic dysfunction  
  • Extremes of age  
  • Cytotoxic chemotherapy  
  • Long term hospitalization  
  • Broad spectrum anti-biotics  
• Superficial candida infections: 

  • Nail infection – paronychia 
  • Develops when candida enters broken skin  
  • Risk – nail biting or working with water  
  • Onychomycosis is fungal infection of nail unit  
  • Risk factors – HIV, diabetes mellitus, age  
  • Are frequent in adult population  
• Diagnosis and treatment of nail infection: 

  • Sample type – scraping or clippings – microscopy + culture 
  • Treatment – Paronychia = topical creams 
  • Onychromycosis – topical creams – 1-3 weeks  

  Oral treatment with itraconazole or terbinafine is 80% effective  

  Treatments takes long due to slow nail growth  
• Tinea Pedis: 

  • Closed shoes regularly, sweat heavily, walk barefoot in infested areas  

  Sample: skin scraping  

  Treatment: Miconazole, Terbinafine 
• Mucosal candida: 

  C.albicans or C.glabrata resident flora of vaginal area 

  • Caused by imbalance of Ph or hormoans  

  Risk factors: pregnancy, diabetes, poor hygiene 

  Is frequently recurring. 

  Symptoms • Itching and irritation around the vagina/ penis head • Soreness during sex or urination • White discharge within the vagina/ penis head 

  Diagnosis – swab for microscopy + culture  

  Treatment – topical azole creams  
• Disseminated candida infections: 

  • Common in hospitalized patients  
  • Can cause blood stream infections  
  • Symptoms: fever, chills, yeast can be isolated  
  • Infection can be spread to the heart  
  • Patients at risk – central venous catheter, diabetics, pre-term babies, long term Abx treatment  

  Diagnosis: 

  • Blood culture or CSF culture  
  • Subculture  
  • Urease test  
  • Chromagar 
  • MALDITOF 
  • Serology  
• Blood is sterile, consists of plasma and cells• The presence of a pathogen in the bloodstream can result in:o Bacteraemiao Viraemiao Fungaemiao Parasitaemia• Pathogens can access the bloodstream via:o Kidneys (ascending UTI)o Infection of tissues e.g., wound/biteo Lungs (during pneumonia infection)
• Types of bloodstream infections

  Transiento Presence of bugs for several minutes rapid removal by immune systemo After dental extraction, urinary catheterisation2. Intermittento Recurrent transient bacteraemia negative blood cultures3. Continuouso Infection that has overwhelmed host defences (cannot be cleared frombloodstream)
• Primaryo Bacterial invasion with no preceding or simultaneous site of infection withsame pathogen2. Secondaryo Isolation of bug from blood as well as other site(s) e.g., wounds, urine,sputum
• Symptoms of bloodstream infections• Fever (>38.3ºC), chills, rigors• BSI = Bacteria/Fungi in blood plus clinical signs andsymptoms of pathogen invasion and toxin production• Full-blown sepsis can develop if not treated quickly
• Sepsis• Is defined as a life threatening condition caused by a dysregulated hostresponse to an infection.o Body’s early response to injury or infection• At least two of the following symptoms:o Body temp above/below normal (<36°C/ >38.3°C)o Heart rate >90 beats per minuteo Hyperventilation >20 breaths per minuteo White blood cell count >12,000 cells/μL (high) or <4000 cells per μL (low)
• Severe sepsiso Dysfunction of ≥ 1 organ plus hypotension• Septic shocko Severe sepsis → extreme low hypotension• All associated with high mortalityo Each hour of delay in antibiotic treatmentresults in increased mortality• Accurate and timely lab diagnosis needed
• Septic shock symptoms• Additional symptoms includeo Extremely low blood pressureo Little or no urine outputo Heart palpitationso Skin rasho Cool and pale limbs
• Disseminated Intravascular Coagulation• Involve both excessive bleeding and clotting• Thrombosis obstruction of blood supply to organs/tissues• Can lead to:o Necrosis of renal cortex/adrenal glandso Gangrene of fingers/toeso Bleeding into subcutaneous tissues• This can lead to Hypotension/shock, Organ failureo Very poor prognosis
• Treatment of Sepsis• Involve both broad-spectrum antibiotics• But once clinical diagnosis made• Switched to more targeted agentso Once more information available about organism in theblood culture• Start to see ↓ inflammatory response (measure CRP, serumlactate)
• infective endocarditis• Infectious endocarditis is the inflammation of the endocardium, the inner lining ofthe heart, as well as the valves that separate each of the four chambers within theheart
• BSI


  Bacteremia, presence of bacteria in the blood, indwelling catheters, IV drug use, oral health problems, diabetes
• Infective Endocarditis


  Infection of the heart valves, bacterial or fungal infection, common causative organisms: S. viridans, S. aureus, risk factors: IV drug use, cardiac surgery, congenital heart disease, valvular heart disease