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Flashcards in Microbiology II Deck (47):

Fungal infections

Fungal infections cause three types of disease:

• infections (mycoses)
• mycotoxicoses
• allergic reactions.

Infections (mycoses)
1. Superficial infections. The commonest encountered surgically is infection of the mucous membrane with yeasts (thrush). Infections of keratinized tissues of skin, nail and hair occur. Abnormalities of toe nails may be caused by fungi.

2. Subcutaneous infections may occur as the result of traumatic implantation of spores leading to local disease with tissue destruction and sinus formation. Such infections are rare in the UK but are more common in tropical regions.


Yeasts: Candida

Candida spp are involved in invasive mycoses. Candida spp, especially Candida albicans are isolated from blood cultures with increasing frequency. Infection is usually endogenous but cross-infection may occur.
Patients at risk include:
• premature babies;
• adults with debilitating diseases, e.g. diabetes;
• immunocompromised;
• transplant patients on immunosuppressive drugs;
• malignancy, especially leukaemia, lymphoma;
• patients on long term broad spectrum antibiotics
or cytotoxic drugs; and
• patients undergoing surgical procedures.


Yeasts: Candida: Clinical

Clinical features
Infection (candidiasis) depends on the host’s suscep- tibility. Minor susceptibility leads to mild, superficial infections, whilst more serious susceptibility leads to deep invasive infections.
Superficial infections include:
• mucous membranes, e.g. thrush – white patches on buccal mucosa, vagina or oesophagus;
• skin, e.g. red weeping areas where skin is moist, e.g. intertrigo in obese patients; and
• deep, e.g. endocardium, heart valves, eye, meninges, kidney, liver, bone.


Yeasts: Candida: Treatment

Superficial infections
Topical preparations, e.g. nystatin or amphoteracin or an imidazole, e.g. miconazole or clotrimazole.

Systemic infections
Intravenous therapy is required, e.g amphoteracin B, flu- cytosine or a combination of both. Oral fluconazole or itraconazole may be used in mucosal or systemic infec- tions. They may also be used prophylactically in suscep- tible patients, e.g. neutropenic or immunosuppressed.
Other yeast infections are rare in surgical patients.


Filamentous fungi


These cause infection of the keratinised tissue of skin, nails and hair, e.g. tinea, ringworm.

Invasive aspergillosis is a well recognised complica- tion of prolonged immunosuppression and is a main cause of death in patients undergoing allogeneic bone marrow transplants. Aspergillus fumigatus is the main pathogen. Aspergillus spp cause a variety of clinical pictures as follows:

• Allergic bronchopulmonary aspergillosis. Inhaled spores cause hypersensitivity reactions, e.g. type I (asthma), type III (extrinsic alveolitis).

• Aspergilloma. Fungal balls grow in existing lung cavities due to TB, bronchiectasis, sarcoid and malignancy.

• Invasive aspergillosis. Usually seen in the immuno- compromised with pneumonia and later spreads to brain, kidneys and heart. Treatment of invasive aspergillosis is with intravenous amphotericin B, caspofungin or voriconazole. Mortality is
high reaching 90% in patients with persistent neutropenia.


Mould pathogens

Pneumocystis carinii
This is a predominant cause of pneumonia in HIV- infected individuals. It may also occur in immunosup- pressed transplant patients. It is usually the result of reactivation of latent infection. A severe pneumonia with progressive dyspnoea and respiratory failure results. Chest x-ray reveals diffuse infiltrates with a ‘white out’ of the lungs. Diagnosis is via demonstra- tion of the characteristic cysts in bronchial aspirates, bronchial lavage or lung biopsy. Treatment is by co-trimoxazole or pentamidine.


Classification of wounds (1 & 2)

Wounds may be classified by their potential for infection:

1. clean: an operation carried out through clean
non-infected skin under sterile conditions where the GI tract GU tract, or respiratory tract are not breached, e.g. hernia repair, varicose vein surgery; the risk of wound infection should be less than 2%;

2. clean contaminated: an operation carried out under sterile conditions with breaching of a hollow viscus other than the colon, where contamination is minimal, e.g. cholecystectomy; the risk of wound infection should be less than 8%;


Classification of wounds (3 & 4)

3. contaminated: an operation carried out where contamination has occurred, e.g. by opening the colon, an open fracture, or animal or human bites; the risk of wound infection is around 12%; and

4. dirty: an operation carried out in the presence
of pus, or a perforated viscus, e.g. perforated appendicitis, faecal peritonitis; the risk of wound infection is 25%.


Hospital-acquired infections

Hospital-acquired infections, or nosocomial infections occur in about 10% of hospitalised patients. The com- monest are UTIs, wound infections, lower respiratory tract infections, and skin and soft tissue infections. Present-day pathogens are often resistant to antibiot- ics, a major problem being methicillin-resistant Staph. aureus (MRSA). Predisposition to hospital-acquired infection includes:

• age – the extremes of life;
• susceptible patients, e.g. immunosuppressed,
diabetic, those with prosthetic implants; and
• modes of treatment, e.g. intravenous lines,
indwelling catheters, etc.
The origin of bacterial infection may be divided into two main sources:
• endogenous – with patient’s normal flora; and
• exogenous – from other people or objects in the


Endogenous infection

This occurs where the organism is carried by the patient either as part of the normal flora or ‘replacement’ flora, i.e. ‘replacement’ organisms which colonise various sites when the patient is treated with antimicrobials. A knowledge of the normal flora present at various sites is important such that distinction may be made from ‘replacement’ organisms which have resulted from antibiotic therapy. The following are examples of normal flora:

• skin – coagulase negative staphylococci and diphtheroids;
• upper respiratory tract – ‘S. viridans’, diphtheroids, anaerobes, commensal neisseriae;
• lower gastrointestinal tract – coliforms, enterococci, pseudomonas, anaerobes (bacteroides, clostridia); and
• anterior urethra – skin flora (as above) or faecal flora (as above).

Commensal bacteria are potential pathogens, and infection may result if the balance is disturbed by a breach of the body defences or if an organism nor- mally a commensal at one site gains access to another site where it is not a commensal: e.g. E. coli, which is part of the normal flora of the colon, gaining access to the urinary tract and giving rise to a UTI. Broad spectrum antibiotics alter the normal flora, inhibiting sensitive organisms and allowing overgrowth of resist- ant bacteria which may result in serious infection. A detailed knowledge of the normal flora is required to distinguish normal flora in culture from pathogens responsible for infection.


Exogenous infection

Exogenous infection is derived either from other people or objects in the environment:
1. people: this may be from medical, nursing, or other patients either from infection, subclinical infection, or asymptomatic carriers;
2 inanimate objects (fomites): these include surgical instruments, anaesthetic equipment, ventilators, humidifiers, and parenteral fluids, particularly if drugs are added under non-sterile conditions; and
3. other sources: these include floors, blankets, urinary bottles, toilets, dust, air and air conditioning systems.



This is a recognized cross-infection problem. Control depends on a combination of hygiene measures such as isolation of patients with diarrhoea and hand wash- ing (alcohol does not kill spores) between contact with patients and careful use of problem antibiotics such as clindamycin and injectable cephalosporins.


Hepatitis B (i)

The hepatitis B virus is a double-stranded DNA virus. The incubation period is six weeks to six months and the period of infectivity is from six weeks before onset of the symptoms and possibly indefinitely thereafter. 10% of patients become chronic carriers. Antigen carriage is a risk for hospital staff, especially those in ‘high risk’ arreas, e.g. theatre staff. Dialysis units are often quoted as being a ‘high risk’ area but following outbreaks many years ago, all staff and patients are tested for HBsAg. Hepatitis vaccine is offered to all high risk healthcare workers. These categories involve surgeons, theatre nurses, pathology department staff, accident and emergency staff, staff in liver transplant units, workers in residential units for the mentally handicapped, staff of GI units and staff of infectious and communicable diseases units.


Hepatitis B (ii)

Hepatitis B may be transmitted by:
• blood transfusion;
• inoculation via sharps injuries from blood or blood products
• droplet transmission
• syringe and needle sharing in drug addicts;
• sexual intercourse with an infected partner;
• homosexual practices
• tattooing, ear piercing, etc. with unsterile

A number of antigen-antibody systems occur relating to HBV. The three viral antigens are:
• HBsAg: hepatitis B surface antigen;
• HBcAg: hepatitis B core antigen; and
• HBeAg: hepatitis ‘e’ antigen.


Hepatitis B (iii)

Following infection, antibodies are formed against all three of the viral antigens but there are important clinical consequences of their identification. Infected persons and carriers have HBsAg and anti-HBcAg but lack anti-HBsAg in their blood. On recovery from infection, HBsAg disappears from the blood and anti- HBsAg becomes demonstrable together with anti- HBcAg. The e-antigen is found only in HBsAg positive sera and appears during the incubation period. The presence of HBeAg (e-antigen) implies high infectiv- ity. Carriers with a persistence of the e-antigen are much more likely to infect others. It has been shown that surgeons who possess the e-antigen may infect their patients during operative procedures.

Clinical presentations of hepatitis B include:
• acute hepatitis with clinical recovery
• acute fulminating hepatitis with death
• chronic active hepatitis with risk of developing cirrhosis and hepatocellular carcinoma.


Hepatitis C

Hepatitis C virus (HCV) is a single-stranded RNA virus. The incubation period is from six weeks to two months. About 0.7% of the population is chronically infected with HCV. Carriers are a source of infec- tion. HCV carriage is seen in drug addicts, recipients of blood and blood products before September 1991 (when testing was instituted), children of infected mothers and healthcare workers from occupational injuries.
Hepatitis B may be transmitted by:

• blood transfusion (before September 1991 in UK);
• syringe and needle sharing in drug addicts;
• mother to baby transmission;
• SHARPS injuries;
• sexual transmission occurs but is uncommon;
• tattooing, ear piercing etc. with unsterile
equipment; and
• sharing toothbrushes and razors.

HCV is identified by antibody testing. About 20% of people infected with HCV will clear the virus in the acute stage but will be antibody-positive. PCR will identify if active virus is still present.
The patient is often asymptomatic. Only about 25% become symptomatic and jaundiced. The severity of the symptoms does not necessarily equate with the extent of the liver disease.
Around 20% of those infected will clear the virus in the acute stage. Of those that do not, some will never develop liver damage. Many will develop only moderate liver damage with or without symptoms. Of the remain- der 20% will progress to cirrhosis within 20 years and of that 20%, some will progress to liver failure and some will develop hepatocellular carcinoma.


HIV (i)

HIV is a single-stranded RNA retrovirus. It produces DNA via the enzyme reverse transcriptase. DNA is incorporated into the host cells. HIV results in wide- spread immunological dysfunction. Infection results in a fall of the CD4 cell numbers and reduction of antigen-presenting cells. Immunological failure results in opportunistic infections and an increased risk of malignancy.
HIV may be transmitted by:
• sexual intercourse (heterosexual intercourse is likely to be the main cause in Africa and Asia; homosexual intercourse in the UK and North America);
• blood transfusion;
• intravenous drug abuse; and • mother to infant.

The following are at risk of becoming HIV positive:
• homosexual or bisexual males;
• prostitutes (male and female);
• intravenous drug abusers;
• haemophiliacs who were treated before routine
testing became available, i.e. October 1995; • sexual partners of the above; and
• children of infected mothers.


HIV (ii)

Asymptomatic viraemia occurs for up to three months after exposure and patients are infective during this period. ELISA test for HIV antibodies is negative at this stage. At seroconversion an acute illness can occur with fever, myalgia and joint pains. An asymptomatic phase then follows. Antiviral antibodies are now pre- sent in the blood and the patient is infective and this phase may continue for many years. Some patients may develop persistent generalized lymphadenopathy following seroconversion which lasts for up to three months with few or no constitutional symptoms. AIDS develops within 5–10 years.

However, an AIDS-related complex may occur before full-blown AIDS occurs. The AIDS-related complex is associated with CD4 cell count of 400/mm2. The virus infects lymphocytes, macrophages and monocytes, i.e. cells that are found in all body fluids. HIV binds the CD4 receptors on T helper lymphocytes (CD4 cells). After a long latent period, up to 8–10 years, the CD4 cell count begins to decline and hence the increase of immunosuppression with a risk of many opportunistic infections and also tumours. AIDS-related complex is characterised by fever lasting more than three months, weight loss, diar- rhoea, anaemia and night sweats. AIDS is diagnosed by the presence of an AIDS indicator disease (see below) with a positive HIV test.

Anti-HIV antibodies appear during the asymptom- atic phase after seroconversion. The CD4 count falls (400/mm2) in AIDS-related complex. The CD4 count thereafter falls further (200/mm2) when AIDS develops.


AIDS indicator diseases are as follows:

• multiple recurrent bacterial infections (see below); • bronchial candidiasis;
• disseminated coccidiomycosis;
• cryptosporidiosis;
• micro-bacterial infection (dissemination);
• CMV infection;
• Histoplasmosis;
• cerebral toxoplasmosis;
• pneumocystis pneumonia;
• invasive cervical carcinoma;
• Kaposi’s sarcoma;
• Lymphoma; and
• HIV encephalopathy.


Sites of bacterial infection in AIDS include:

• boils, carbuncles, cellulites;
• anorectal abscesses;
• empyema thoracis;
• necrotising fasciitis;
• osteomyelitis;
• septic arthritis;
• epididymo-orchitis; and
• pelvic inflammatory disease.



Immunisation is available against hepatitis B but not hepatitis C or HIV. Hepatitis B vaccine is offered to all high-risk staff. Categories of high-risk staff include:
• surgeon;
• theatre nurses;
• other operating department personnel;
• pathology department staff;
• A & E staff;
• liver transplant unit staff;
• GI unit staff;
• workers in residential units for the mentally
handicapped; and
• staff of infection and communication diseases units.
Dialysis units are often quoted as being ‘high-risk areas’. However, following outbreaks of hepatitis B several years ago, all staff and patients of dialysis units are tested for HBsAg.


Post-exposure prophylaxis: Hepatitis B

If the source patient tests positive for HBV, the vac- cinated healthcare workers should be tested for anti- body to HBV. If antibody levels are low, a dose of hyperimmune anti-hepatitis B IgG plus one dose of vaccine should be given. In the unvaccinated, one dose of hyperimmune anti-hepatitis B IgG should be given and a course of HBV vaccinations commenced. Similar procedures should be followed when the source patient cannot be identified or refuses to be tested.


Post-exposure prophylaxis: Hepatitis C

Hepatitis C
There is no vaccine or specific treatment for this. Immune serum globulins should be offered as prophylaxis.


Post-exposure prophylaxis: HIV

HIV testing should be carried out after counselling at three months and six months after injury. There is no vaccine available. Zidovudine may be given to workers with deep needle stick injuries who are exposed to large volumes of blood. There is however, no hard evidence that Zidovudine will stop HIV infection development. The drug is highly toxic and should not be used dur- ing pregnancy or breast-feeding. Side effects include nausea, malaise, fatigue, headache and bone marrow suppression.


Disinfection: Betadine

Disinfection is a process used to reduce the number of viable micro-organisms. It fails to inactivate some bac- terial spores and some viruses. Disinfection has to be distinguished from cleaning, which is a process which physically removes contamination but does not neces- sarily inactivate micro-organisms. The efficacy of dis- infection depends on several factors: for example, the length of exposure, or the presence of blood, faeces, or other organic matter which may reduce the efficacy of the disinfection process. Some examples of disinfec- tion are given below:

• Povidone-iodine (Betadine). This has wide antibacterial spectrum. It is useful for preoperative skin preparation of the patient and as a surgical scrub solution.


Disinfection: Hypochlorite

• Hypochlorite (Milton, Eusol). Hypochlorites have a wide antibacterial spectrum, including viruses. They are inactivated by organic matter.


Disinfection: Chlorhexidine

• Chlorhexidine (Hibitane). This is active against Gram positive bacteria. It is usually used as a 0.5% solution in 70% ethanol or in water. Unlike iodine it is devoid of the risk of irritation of the skin and sensitisation.


Disinfection: Triclosan

• Triclosan (Aquasept). This is active against Gram positive and some Gram negative bacteria. It is usually used as a 2% aqueous solution. It can be used as a bath concentrate for prevention of cross infection and secondary infection (ster-Zac® bath concentrate).


Disinfection: Quaternary ammonium salts

• Quaternary ammonium salts (Cetrimide). Quaternary ammonium compounds are active against Gram positive bacteria. They have no action against Pseudomonas. They are weak disinfectants.


Disinfection: Formaldehyde

• Formaldehyde. Formaldehyde has a wide antibacterial spectrum, including viruses. Formaldehyde is a hazardous substance. It is irritant to the eyes, respiratory tract, and skin. Aqueous 10% formaldehyde can be used to disinfect contaminated surfaces. If used as a gas it needs to be used in an air-tight cabinet.


Disinfection: Glutaraldehyde

Glutaraldehyde (Cidex). This has a wide antibacterial spectrum, including viruses. It kills spores slowly. Penetration is poor and it is irritant and may cause hypersensitivity.


Disinfection: Boiling water

• Boiling water. This is an efficient disinfection process which kills bacteria, including TB, some viruses, including HBV and HIV, and some spores. Items for disinfection must be thoroughly cleaned and totally immersed in the boiling water. It is suitable for proctoscopes and sigmoidoscopes.


Disinfection: Pasteurisation

• Pasteurisation. This can be used for foodstuffs such as milk which can be disinfected but not sterilised by moist heat. Milk is held at 63–66oC for 30 min. Most non-spore-forming pathogenic bacteria, including Mycobacterium tuberculosis, brucellae, campylobacter and salmonellae,
are killed.



The development of SIRS is mani- fested by two or more of the following criteria:
• temperature above 38oC or below 36oC (rectal);
• tachycardia above 90 bpm;
• tachypnoea – respiratory rate above 20 breaths per
minute or a PaCO2 of less than 4.3 kPa; and
• WBC above 12,000 cells per mm3 or below 4,000
cells per mm3 or 10% of immature forms.
Sepsis is described as SIRS with a documented infec- tion and severe sepsis as SIRS with a documented infection and haemodynamic compromise. It should be noted that immunocompromised patients can be septic without eliciting an inflammatory response. Multiple organ dysfunction syndrome (MODS) is a state of physiological derangement in which organ function is not capable of maintaining homeostasis.
There is a continuum from the development of SIRS to the onset of sepsis and progression to shock and multiple organ dysfunction. The identification of SIRS alone in a patient on ITU has a poor specificity for predicting the development of sepsis and septic shock. However, there is an increasing incidence of organ system failure as patients progress from SIRS to septic shock.


Stages of SIRs: I

Three stages have been described in the development of SIRS:
• Stage I – In response to a local insult, the local environment produces cytokines which provoke
an inflammatory response, promote wound repair, and recruit cells of the reticulo-endothelial system.


Stages of SIRs: II

• Stage II – Small quantities of cytokines are released into the circulation to enhance the local response. Macrophages and platelets are recruited, and growth factor production is stimulated. An acute phase response occurs which is controlled by a simultaneous decrease in pro-inflammatory mediators and release of endogenous antagonists. These mediators hold the initial inflammatory response in check. This continues until the wound is healed, the infection resolves and homeostasis is restored.


Stages of SIRs: III

• Stage III – If homeostasis is not restored,
stage III (SIRS) develops. A massive systemic reaction occurs, cytokines becoming destructive rather than protective. Inflammatory mediators trigger numerous humoral cascades, resulting in sustained activation of the reticulo- endothelial system with loss of integrity of the microcirculation and dysfunction of various distant end-organs.


SIRs consequences

The destructive systemic and regional responses to SIRS, i.e. increased peripheral dilatation, excessive microvascular permeability, accelerated microvascular clotting, and leucocytes/endothelial cell activation, con- tribute to pathological changes in various organs and are considered the major aetiological factors in the devel- opment of septic shock, ARDS and MODS. Changes associated with MODS include fever, hypermetabolism, anorexia, protein catabolism, cachexia, and altered fat, glucose and trace element mineral metabolism. These processes are accelerated in the presence of a second insult, e.g. shock, infection, ischaemia following the initial trauma. Mediators of SIRS include endotoxin, TNF’ and interleukins, chiefly IL-1 and IL-6. Cells involved include endothelial cells and leucocytes, espe- cially neutrophils. Secondary inflammatory mediators include arachidonic acid metabolites, nitric oxide, and platelet-activating factor (PAF).


Sepsis and multiple organ failure

Multiple organ failure is a final common pathway associated with the consequences of severe infection, severe tissue injury or shock. The primary precipitat- ing events have been dealt with above. Factors leading to multi-organ failure include:

• excessive release of endogenous mediators, including TNF’, IL-1, IL-6;

• impaired local microvascular perfusion interfering with O2 delivery to tissues with disruption of
cellular metabolic functions;

• impaired intestinal barrier function with bacterial translocation releasing endotoxins into the portal circulation and to the liver;

• damage to reticulo-endothelial function;

• immune depression with T and B cell depression

• T-suppressor cell stimulation, resulting in increased vulnerability to infection.

The target organs of cytokines include the lung, car- diovascular system, kidney, liver, gastrointestinal tract, brain, reticulo-endothelial system and immune system.


Sepsis and respiratory system

The respiratory system is often involved. The patient will be hypoxic and show symptoms of respiratory failure. Acute respiratory distress syndrome (ARDS) may result (see below). Nosocomial pneumonia occurs in 70% of patients.


Sepsis and cardiovascular

Endothelial damage leads to interstitial oedema. There is also vasodilatation leading to hypotension. Tissue hypoxia results in lactic acidosis. Myocardial dysfunc- tion occurs due to the effects of inflammation, circu- lating myocardial depressant factor and endotoxins.


Sepsis and Renal

Oliguria occurs (0.5 ml/kg/hr urine production). There will be elevation of the blood urea and creatinine.


Sepsis and Hepatic

Hypoperfusion of the liver results in reduced metab- olism of drugs and hormones. Poor control of glu- cose homeostasis and failure of synthetic function, e.g. clotting factor, resulting in coagulopathies. There is also failure to conjugate bilirubin and hypobilirubi- naemia results.


Sepsis and Gastrointestinal

Atrophy of the mucosa occurs due to hypoperfusion and ischaemia. There is an increased risk of bacteria translocation into the portal system, stimulating liver macrophages to produce cytokines with amplification of SIRS.


Sepsis and Cerebral

There may be confusion, agitation, stupor, coma, the above being due to hypoperfusion, septic encephalop- athy or metabolic encephalopathy.
There may be anaemia, leucopenia, thrombocytopenia or leucocytosis. Clotting screen may show a range of abnormalities from prolonged APTT and PT to frank disseminated intravascular coagulation (DIC).


Sepsis and Metabolic

Hypoglycaemia may occur due to sepsis and catechol- amine release (both cause insulin resistance). Lactic acidosis will result and there will be a generalised cata- bolic state.
If MODS continues unchecked, then organ dysfunc- tion will become irreversible. At this state multi-organ failure is said to have occurred. This progression is potentially preventable with appropriate treatment.


Principles of treatment of sepsis syndrome

Attempts to abrogate SIRS may be approached in three ways:
• eradication of source of infection;
• treatment of sepsis-associated cardiovascular,
metabolic and multi-organ disturbances; and
• inhibitors of toxic mediators, e.g. anti-TNF’, anti-
interleukin 1.