Communityacquired (most common)

Major route of infection ascending; through urethra, bladder, through ureter to kidneys (responsible for 30-40% of hospital-acquired infections) Major disposing factor: Catheterization

Hospitalacquired

URINARY TRACT INFECTIONS Urine: source of nutrients, ph 5-6, good bacterial growth medium More common in females because of urogenital tract anus vagina urethra bladder ureter During insertion, bacteria may be carried directly into bladder In situ catheter facilitates bacterial access to bladder  Via lumen of catheter  Tracking between outside of catheter and urethral wall

80%: e. coli; 10%: coagulase-negative staphylococci; 5%: proteus mirabilis; 3%: other gram ve; 2%: other gram +ve;

Catheter may become colonized with bacteria biofilm formation o Long-term catheterization > 5days 50% chance of infection Remove catheter clear infection

Host defence against UTI Predisposing factors to UTI anything that:

Most susceptible hosts

Mechanical processes to prevent bacterial colonization of urinary tract: flushing effects of urination; epithelial cell shedding; sphincter action Disrupts normal urine flow Why is urine screened for infection in Impairs free drainage of urine pregnancy? Causes injury to mucosa of urinary tract Facilitates access of organisms into bladder Women (20-40 years old): - Children: anatomical abnormalities of the sexual activity enhances entry urinary tract; uncircumcised male infants of faecal bacteria into the  symptoms are often non-specific: urinary tract fever, irritability, incontinence, Pregnant women: diarrhea, lack of appetite Hormonal changes: - Males (>60 years old): prostate Progesterone-induced hypertrophy ureteral dilation Growing foetus : Pressure of expanding uterus against the ureters

40%: e. coli; 25%: other gram ve; 16%: other gram +ve, 11%: proteus mirabilis; 5%: candida; 3%: coagulase-negative staph - Biological (Immune system: less important than mechanical processes) - Pregnant women have higher risk of UTI - Early stage of infection may be asymptomatic (increased risk of pyelonephritis) - UTI and pyelonephritis septicemia; may result in premature delivery - Calculi (little stone/pebble): may form in any part of urinary tract - Loss of neurological control of bladder: spina bifida; paraplegia; multiple sclerosis - incomplete bladder emptying - urinary reflux - tumours - contraceptive diaphragms - diabetes - instrumentation of lower urinary tract

1|P a ge

URINE SAMPLES Mid-stream urine (MSU) reduces contamination of urine with bacteria and epithelial cells present in urethra Procedure Clean surrounding area with saline swabs; do not Allow first 20-3ml of urine to escape Collect next 50ml in use antiseptics sterile container Babies and young Bag urine: subject to contamination Suprapubic aspirate: avoids contamination Detection of any bacteria children is clinically significant Catheterised Urine drawn from catheter port with sterile patient syringe and needle Storage and Immediately after collection, urine should be If patient is on antibiotics, note this on request transport stored at 4 degrees celcius to prevent any form organisms in urine from multiplying no. of bacteria in urine is critical for correct diagnosis Urine analysis Biochemical screening rapid detection of blood, WBC, protein, nitrite, pH, glucose etc. DIAGNOSIS OF UTI Findings required: - MSU interpretation  Probable contamination y 2 species, both >10^8/L, polymorphs NOT elevated, increased no. of squamous epithelial cells y 10^7-10^8 organisms/L, 2 bacterial species, with or without elevated polymorphs - Consistent with UTI  At least 10^8/L organisms; one bacterial species isolated; polymorphs elevated to >100x10^6/L - Likely UTI  2 bacterial species; at least one organism at least 10^8/L; polymorphs elevated to >100x10^6/L  Report identity and sensitivities of major species Macroscopic Red, clear Red, cloudy Yellow, cloudy Microscopic - Bacterial count Red cell count (abnormal/contaminant) Epithelial cell count (>20 examination - White cell count (presence of - UTI epithelial cells per high PMN) - Endocarditis, renal trauma, calculi, urinary carcinomas, power field = contamination) >100x10^6/L abnormal clotting disorders, thrombocytopenia, menstruation, catheterization, instrumentation, aspirin, anticoagulants Culture (MCS) Allows quantitation; determines Culture on MacConkey agar streaking, quantitation Antibiotic sensitivity bacteria types; identifies (urostrips) testing causative agent - Guides treatment Quantitation Not delivered promptly or badly Probable infections but require confirmation: Infected: 10^5-10^7 contaminated: 10^3-10^4 10^4-10^5

2|P a ge

Complicated UTI: Associated with anatomical/functional abnormalities; increased risk of serious complications or treatment failure Signs and symptoms Treatment - Dysuria (pain on urination): irritation/swelling in Non-pregnant women the bladder (may be caused be infection) - Generally treated empirically with (TCAC) - Frequency (need to urinate more often, Trimethoprim/ Cephalexin/ Amoxycillin + accompanied by increase in total daily amount of Clavulanate/ Nirofurantoin urine) - If treatment fails Urine culture and antibiotic - Urgency (sudden urge, accompanied by discomfort susceptibility testing in bladder) Pregnant women - Possible supra-pubic pain (above pubic symphysis) - Urine culture and susceptibility testing - NO TRIMETHOPRIM Acute Inflammation - Systemic symptoms (fever, chills, nausea, vomiting) - *** Culture and sensitivities *** pyelonephritis of kidneys - Possible flank pain (lumbar region) - Mild infection (low grade fever, no nausea or - Onset of symptoms is typically rapid vomiting): TCAC (orally) - Severe infection (sepsis / vomiting): *** Immediate empiric therapy *** of Gentamicin (IV) + Ampicillin (IV) Switch to oral therapy asap. Urethral syndrome - Symptoms of cystitis (Cause unknown) - Difficulty in starting urination slow stream Hormonal imbalances, urethral stenosis, - Feeling of incomplete emptying of bladder environmental chemicals, traumatic sex - Sterile urine culture no bacteria Asymptomatic bacteruria (pregnant) Only detected by screening; significant bacteria in urine MORE THINGS TO TAKE NOTE OF Colonization Adhesion Typical clinical presentation st requirement: UPEC: Urinary 1 Adhesins most important - 23-year-old woman pathogenic e.coli sources of UPEC - Protect bacteria from urinary lavage - 2 day history of frequency, dysuria, slight hematuria Colonisation strong in colon - Increased ability to multiply and invade - Suprapubic pain inflammatory 2nd: entry & Major E.coli-associated adhesins - No vaginal discharge response symptoms colonization of - Type 1 pili: vital for attachment to bladder - No relevant history; unremarkable physical exam of acute UTI vagina and/or - Pyelonephritis-associated pili (P pili) - What factors suggest UTI? urethra Attach to receptors in kidney - What specimens should be collected? Recurrent UTI Common in young (27-44% women with initial UTI: 1 recurrence Reinfection; persistent focus of infection; formation of healthy women in 6 months despite antibiotic therapy) intracellular communities Catheter-associated - Catherise for shortest time possible infections - Remove catheter when possible (intermittent better than continuous use) Only treat if signs and - Change infected catheter immediately - Encourage increase in fluid intake symptoms present

Uncomplicated UTI: Adult nonpregnant women UTI Definition Acute Inflammation uncomplicated of bladder cystitis

3|P a ge

Type Superficial

Site Hair shafts; dead layer of skin; outermost layers of skin (stratum corneum)

Examples Mycoses (PityriasisVe rsicolour) Common fungal infection of skin Mycoses (Tinea/Der matophytosi s ringworm)

FUNGAL INFECTIONS Causative agent; Symptoms - Malassezia furfur (Yeast) - Common inhabitant skin - Changes from commensal to pathogen (phase change from yeast hyphal form of fungus; stimulus unknown) Flaky discoloured patches; confined to trunk and proximal part of limbs; uncommon in other parts of body Hypo or hyper-pigmented lesions; coalesce to form scaling plaques; not normally itchy May resolve spontaneously Dermatophya fungi/dermatophytes (in the three genus: Epidermiphyton, Trichophyton, Microsporum) Source of infection: humans, soil, animals Can be transmitted from feet through desquamated skin scales shed in carpet, matting, showers Infection spread by contact with arthrospores (asexual spores) which attach to keratinocytes and invade Dermatophytes can utilize keratin as nutrient source using its unique enzyme capacity from keratinase no living tissue is invaded; keratinized stratum corneum is simply colonized presence of fungus and its metabolic products allergic and inflammatory eczematous response

Cutaneous

Epidermis; hair; skin; keratinised layers of epidermis, nails and hair

Tineapedis Tineabarbae Tineacapitis Onychomycosis Diagnosis of dermatophyte infections

- Typical symptoms: annular lesions; scaling; raised margin - Main symptom: itching Athelete s foot ; marked erythema of 1st and 2nd toes; toe-web maceration and minimal inflammation Affects beard area Affects hair and skin of scalp Infection of keratinized layer of nails; in 3% of population; increases to 5% in elderly - Clinical assessment: based on clinical grounds - Specimen collection: skin scraping from leading edge of lesion - Microscopy: examine structure of fungus; presence/absence of asexual spores, size, shape, site - Culture: Sabourauds (SAB) sugar; pigment formation and mycelial form o Epidermiphytonfloccosum: infects skin (tineacorporis, tineacruris, tineapedis) and nails o Trichophytonrubrum: one of most common causes of Tinea; infects skin, hair, nails; produces pigment; mycelium (many hyphae) o Trichophytonmentagrophytes: infects feet, hands, groin; inflammatory lesions of scalp, nails, beard o Microsporumcanis: occurs on scalp and glabrous skin (smooth, hairless); cause of ringworm in cats and dogs

4|P a ge

Subcutaneous Dermis, subcutis

Sporotrichosis

Mycetoma Systemic Internal organs Coccidioidomy cosis

Blastomycosis

Histoplasmosis

Opportunistic Internal organs

Candidiasis

Oral candidiasis

Vaginal/Vulvo vaginal candidiasis

Sporothrixschenckii;from soil, plants; infection acquired through trauma Small papules/sub-cutaneous nodules at site of trauma Spread of infection produces a series of secondary nodules along lymphatics Disseminated disease can occur Commonly madurella species (endemic in Africa) Chronic infection of subcutaneous tissue Coccidoidesimmitis(soil, endemic in south-western USA, northern Mexico) Primarily a pulmonary disease; results from inhalation of conidia (spores) o 60% suffer benign chest infection o 40% develop typical symptoms of pulmonary fungal disease anorexia, weight loss, cough, hemoptysis - 5% progress to systemic disease (meninges, bones, joints, subcutaneous & cutaneous tissues) - Blastomycesdermatitidis(restricted to North America, recently in Africa, Asia, Europe) - Symptomatic in only 50% of cases - Chronic granulomatous disease: progresses slowly - Primary pulmonary involvement - Flu-like illness (fever, chills, productive cough myalgia, arthralgia, pleuritic chest pain) - Haematogenous spread cutaneous lesions in skin/bone in >70% of patients - Histoplasmacapsulatum(world-wide, majorly endemic in Mississippi-Ohio River Valley) - Intracellular infection of reticuloendothelial system - Inhalation of conidia from soil enriched with chicken, starling and bat exreta - 95% of cases are inapparent, subclinical, benign - 5% of cases chronic progressive lung disease; chronic cutaneous/systemic/acute fulminating fatal systemic diseases - Members of the Candida genus (C. albicans most common; C. glabrata etc.) - Acute, subacute, chronic or episodic clinical manifestations - Localized to mouth, throat skin, vagina, fingers, nails, bronchi, lungs, GIT - Or become systemic (septicemia, endocarditis, meningitis) - Broad spectrum of antibiotics changes balance of normal flora of oral cavity C. albicans flourishing - Superficial infection, usually responds to treatment In newborn babies - Characteristic patches of a creamy-white to grey pseudomembrane - Mouth of normal newborns has low pH C. albicans proliferate - Infections acquired during birth (mothers with vaginal thrush during pregnancy) - Nursing mothers C. albicans infection of nipples severe pain when feeding (ping-pong: mum-baby-mum) - Vaginal thrush (75% of women at least 1 occurrence in their lifetime) - Most commonly C. albibans normal flora - Opportunistic due to prolonged broad spectrum antibiotics, diabetes, douching, pregnancy, contraceptive pill - May be sexually transmitted to partner (penile colonization in 20% of male partners of infected women; usually asymptomatic; but if not symptoms = balanitis)

5|P a ge

Systemic candidiasis

Cryptomycosis

At risk patients: o lymphoma and leukemia o cell-mediated immune deficiency; o patients receiving aggressive cancer treamtment, immunosuppression and transplantation therapy C. albicans usually acquired via GIT infections; IV catheter-related infections Blood-bourne spread to almost any organ Diagnosed @ lab using o microscopy (wet mount; gram stain) o culture (sabouraud s medium) o germ tube test (C. albicans +ve; C. glabrata and C. parapsilosis ve) Cryptococcus neoformans (encapsulated yeast) Source: bird shit (pigeons) Inhalation of airborne cells Primary infection in lung pneumonia Immune-suppressed patients; invade bloodstream from primary site cryptococcal meningitis o Most common cause of worldwide fungal meningitis o 7-10% of AIDS patient affected: CD4 lymphocyte count <200/mm^3 increased risk Symptoms develop slowly over several months Initial headache, then drowsy, dizzy, irritable, confused, nausea, vomiting, neck stiffness, focal neurological defects Later stages of infection diminishing visual acuity, maybe coma Diagnosed @ lab using o Microscopy: india ink preparation o Culture: sabouraud s dextrose sugar o Colonies: cream, smooth, mucoid o Cryptococcal antigen test: rapid latex agglutination test to detect capsular polysaccharide antigens of C. neoformans; serum and cerebrospinal fluid Aspergillusfumigatus/flavus Non-invasive pulmonary disease in patients with pre-existing lung cavities/chronic pulmonary disorders o Aspergilluscolonises cavity fungal ball aspergilloma Invasive pulmonary disease in immune-compromised hosts Hematogenous dissemination in those severely immunosuppressed or with IV drug addition Causes thrombosis and infarction when blood vessels are invaded Pneumocysticjiroveci (yeast-like fungus) Common cause of interstitial pneumonia High fever, non-productive cough, shortness of breath, weight loss, night sweats, limited sputum production Affects immunocompromised hosts (AIDS, patients on immunosuppressant medication) Rare in people with normal immune systems; may be found in lungs but NO disease

Aspergillosis

Pneumocystis pneumonia

6|P a ge

TREATMENT OF FUNGAL INFECTIONS Know the structure of fungal cell Sites of action of common Polyenes integrate into cell membrane antifungal agents Azoles Major uses: superficial mycoses and candidiasis Mode of action: block production of ergosterol with inhibition of enzyme lanosterol C14-demethylase accumulation of toxic sterol intermediates cell membrane stress Flucytosine interrupt DNA and RNA synthesis Oral: Fluconazole To treat: Candida oesophagitis Vaginal candidiasis (unresponsive) Severe oral candidiasis Onychomycosis Azoles interrupt steroid biosynthesis (cell and mito membrane) Topical: Bifonazole, Clotrimazole, Econazole, Ketaconazole (shampoo for seborrhoeic dermatitis and dandruff), Miconazole To treat: Tineapedis, tineacorporis, pityriasisversicolour (superficial mycoses) and some candida infections (balanitis, vaginal thrush) Nystatin (topical agent) Poorly absorbed from FIT Not absorbed through skin/mucous membranes when appliced topically Mainly active against C. albicans (Vaginal/oral thrush) 5-Flucytosine Developed in 1950s as potential anticancer agent; later found to be anti-fungal Mode of action: inhibits DNA and RNA synthesis Active against yeasts, used for cryptococcal infection Resistance develops rapidly, used in combination with Amphotericin B

Polyenes

2 major ones: Amphotericin B (for serious systemic infections, given through IV) Nystatin (topical agent) Mode of action: inhibit cell membrane function by preferentially binding to ergosterol (a cholesterol) toxic effects

Amphotericin B To treat cryptococcal meningitis Toxic administer saline prior to amp B to limit toxicity Side effects: renal toxicity

7|P a ge