Wednesday, June 15, 2011


The word sepsis has its origin with the Greeks, who postulated two fundamental forms of tissue breakdown: pepsis was a process exemplified by the fermentation of wine or the digestion of food and was associated with life and good health: sepsis, on the other hand, described the processes of putrefaction and decay and was associated with death and disease (Majno, 1991). With the recognition that microorganisms were agents of putrefaction, the word (sepsis) was applied to the clinical condition resulting from bacterial infection, and the neologism septicemia denoted the presence of these organisms in the blood stream.

Sepsis has traditionally been considered synonymous with "disseminated infection" because microbial toxins were thought to be a prerequisite for the development of fever, tachycardia, and tachypnea, the clinical signs of serious infection.

The classic clinical syndrome of sepsis was originally described in patients with disseminated gram-negative bacterial infections (Maclean et al., 1967). Later it became apparent that an identical syndrome developed in patients with gram positive bacterial (Wiles et al., 1980) or Viral; (Deutschmann et al., 1987) infection in association with salicylate intoxication (Leatherman et al., 1991), and even in normal volunteers who received an infusion of sterile stress hormones (Watters et al., 1986).

Sepsis is one of the main causes of morbidity and mortality in the intensive care units (ICU) (Bone et al., 1989). A delay in making the diagnosis and instituting appropriate therapy has been associated with increased mortality. Moreover, its diagnosis is frequently difficult since clinical signs of sepsis are often misleading and/or absent and, in addition, traditional markers of infection such as body temperature (BT) and white blood cell count (WBC) can remain unchanged, mainly in the early stage of the process (Springer and Verlag, 1998). Septicemia is a clinical syndrome characterized by fever, chills, malaise, tachycardia, hyperventilation and toxicity or prostration, (Failure to thrive) may indicate chronic septicemiae in infants (Shanson, 1999).

In the early stages, the clinical features may be very varied, especially in infants. Prompt recognition of septicemia and immediate treatment based on the knowledge of the likely causative organisms is essential. Complications include septic shock, disseminated intravascular coagulation (DIC) and acute renal failure. The mortality rate depends on the age, the underlying condition and the treatment given, in many series the mortality rate varies between 15% and 35% (Shanson, 1999).

1.2 How bacteremia occurs:

The blood is normally sterile, bacteremia occurs when microorganisms enter the blood stream. Bacteremia may be transient, intermittent or continuous (Koneman et al., 1997).

Transient bacteremia may occur when organisms, often comprising the normal flora, are introduced into the blood (e.g., following brushing of teeth) (Koneman et al., 1997).

Intermittent bacteremia occurs when bacteria from an infected site are released into the blood from extravascular abscesses, empyemic cavities, or diffuse infections, cellulites, peritonitis and septic arthritis (Koneman et al., 1997).

Continuous bacteremia usually occurs in cases where organisms have direct access to the blood stream such as subacute bacterial endocarditic, infected arteriovenous fistulas, intra-arterial catheter, or indwelling cannulae (Kaneman et al., 1997).

Also bacteremia was classified as primary if it occurs in the absence of an apparent portal entery, and secondary if a portal of entery was identified (Koneman et al., 1997).

Several mechanisms play a role in the removal of microorganisms from the blood stream. In healthy and immuno competent hosts, a sudden influx of bacteria is usually cleared from the blood within 30 to 45 minutes. The liver and spleen play the primary role in clearing bacteria ; intravascular phagocytes play only a minor role. Encapsulated bacteria are more difficult to clear ; however, the presence of specific antibodies promotes clearance (Koneman et al., 1997). Patients with debilitating or immuno deficiency diseases are at higher risk because the circulating bacteria may not be cleared from the blood for hours (Eykyn, 1998).

1.3. Causative organisms:

The relative incidence of the different causative organisms varies between hospitals according to the specialties practiced, the incidence of hospital infection and the type of community served by each hospital hence, the most frequent organisms causing bacteremia varies, both nationally and internationally (Shanson, 1999).

The most common causative organisms of bacteria are discussed below:

1.3.1. Gram negative septicemia:

The organisms most commonly isolated from blood are Gram-negative rods including Enterobacteriacease and Pseudomonas species E.Coli is by far the most frequent cause of this condition. The majority of these episodes results from urinary tract infection, other occur with biliary infections (Eykyn, 1998).

¬The release of endotoxin from Gram-negative organisms may result in septic shock (Crichton, 1993).

Immunocompromised patients tend to be colonized with bacteria that are relatively antibiotic resistant such as serratia marcescens, Enterobacter species and Pseudomonas aruginosa (Bailey and Scott, 1994.

Salmonella bacteremia frequently develops in patients with severe salmonella gastro-intestinal tract infection particularly in infants, elderly and debilitated patients leading to high mortality rate. Metastatic infective complications may occur such as meningitis, skin infection, splenic abscess, pyelonephritis, and very rarely Pneumoniae and Endocarditic (Shanson, 999).

Haemophilus influenzae can be isolated from blood particularly as an etiologic agent of endocarditic (Shanson, 1999).

Many factors predispose to Gram-negative septicemia including instrumentation and surgery on the gastrointestinal and urinary tracts, and neutropenia in oncology or transplanted patients Fig. (1). The incidence of Gram-negative sepsis in hospitals and also the effects of widespread use of broad-spectrum antibiotics, such as ampicillin, in promoting infections due to antibiotic-resistant strains (Shanson, 1999).

Fig.1. Venn diagram showing the possible interactions of four important groups of factors predisposing for Gram-negative septicemia (Shanson, 1999).


e.g.,Gram-negative bacilli invade blood from a site with normal flora, such as the gut


e.g., Surgery on carcinoma of the colon Cystoscopy Intravenous infusion therapy IMPAIRED HOST DEFENCES

e.g., Severe neutropenia and immunosuppressive therapy low birth weight and prematurity.


e.g., Urinary tract infection Gram-negative pneumonia Gram-negative infection of burns

1.3.2. Gram positive septicemia:

Staphylococci and streptococci cause the majority of Gram positive septicemia which usually complicate infections of the skin, soft tissue, bones, joints and lungs (Shanson, 1999).

Staph aureus infection at any site of the body can result in staphylococcal bacteremia which is always symptomatic, high grade and potentially lethal. Staph. aureus bacteremia has its highest frequency in the very young and the very old with serious underlying diseases and intravenous drug abusers (Dalton and Nottebart, 1986).

The septic shock and disseminated intravascular coagulation that can complicate staphylococcal septicemia may be due to the effect of its protein A (Roberts and Gaston, 1987).

An increasing proportion of blood stream infections due to coagulase negative staphylococci, enterococci has been documented in recent years. It reflects changing in, hospital people population and increasing use of invasive devices (Eykyn, 1998).

Coagulase negative staphylococci are especially important in the pediatric age group and were responsible for 43% of bacteremia in Great Ormond hospital, London. It is the third most common blood stream pathogen after group B streptococci and staph aureus in a Swedish neonatal unit (Eykyn, 1998).

The -hemolytic streptococci or viridans streptococci, comprise a heterogenous collection of species of which streptococuus sanguis I and II, streptococcus mutans and streptococcus mitis are most frequently isolated from cases with endocarditis. These organisms are normal inhabitants of the oral cavity and gastrointestinal tract (GI, II) often gaining enterence to the blood stream be cause of gingivitis or dental manipulations (Shanson, 1999).

Heart vavles especially that previously damaged convenient surfaces for attachment of the bacteria. The resulting vegetations uttimately seed bacteriae into the blood at a slow but constant rate (Scheld and Sande, 1990).

Group A B-hemolytic streptococci was a frequent cause of endocarditis during the pre-antibiotic era. It may occasionally cause fulminating septicemic infections, generally in previously healthy often young people (Dalton and Nottebart, 1986).

Adult group B-streptococcal bacteremia is associated usually with underlying disease as diabetes mellitus, neoplasm and urinary tract infection (Shanson, 1999).

Group D streptococci may be -- or non hemolytic and are separated into two divisions: enterococci and non enterococci. Of the enterococci, streptococcus faecalis is the most frequent human pathogen among debilitated and immuno suppressed adults. They are normal inhabitants of the gastrointestinal and genitourinary tracts of man (Dalton and Nottebart, 1986).

Septicemia occurs in 25-30%of patients with penumococcal pneumonia and this makes the prognosis worse. Because the organism produce autolytic enzyme, early subculture of broth (before 18 hour) is necessary (Bailey and Scoot, 1994).

Listeria monocytogenus is a cause of septicemia in immuno suppressed patients, alcoholics, and pregnant women. The bacterium may resemble a diphtheroid or coccus in Gram stain, but grows on 5% sheep blood agar as a translucent weakly B-hemolytic colony resembling B streptococci, so listeria must be distinguished from diptheroids and from group B and D streptococci. It displays a characteristic tumbling motility at room temperature but not at 35oc (Bailey and Scott, 1994).

Corynebacterium group IK should be suspected if a diptherid like bacterium is isolated from blood cultures usually of debilitated and immunocompromised patients and displays an unusual broad antibiotic resistance pattern, often being sensitive only to vancomycin (Shanson, 1999).

Members of this group of organisms exist as components of the normal skin flora especially at axillary, inguinal and rectal regions (Bailey and Scott, 1994).

The clinical features and complications of septicemia due to Gram-positive organisms may be indistinguishable from those due to Gram-negative organisms the septic shock and disseminated intravascular coagulation that can complicate staphylococcal septicemia may possibly due to the effects of protein A of staph aureus. Metastatic abscesses and acute infective endocarditis affecting a previously healthy arotic valve can also complicate Staph. aureus septicemia (Shanson, 1999).

1.3.3. Anaerobic septicemia:

Anaerobic bacteria originate from the normal flora of the mucosal surfaces (Collee et al., 1996).

Organisms of the genus peptostreptococcus have been reported from most review of blood culture. It may occasionally invade the blood from an infected female genital tract or oral sepsis (Bailey and Scott, 1994).

Bacteroides fragilis and other bacteroides are the main causes of anaerobic septicemia. These species can clinically cause septicemia that is indistinguishable from that produced by aerobic Gram-negative septicemia. Abdominal or gynaecological sepsis is usually present and bacteroides may be mixed with E.coli or other coliforms in the blood (Shanson, 1999).

Clostridium perfringens can cause rapidly fatal disease with severe toxaemia, hemolysis, shock, jaundice and acute renal failure. It must be presumptively identified by Gram stain appearance, gas and hemolysis in broth so that the clinician can be alerted to the possibility of the presence of this virulent bacterium in the blood stream (Bailey and Scott, 1994).

1.3.4. Other bacteria such as:

Campylobacter species especially campylobacter fetus, Alealigenes species, Eikenella Corrodens and flavobacterium species. If these less common organisms are suspected by the clinician, the laboratory can be alerted to hold the blood culture media for an extended period of time past the first week (Biley and Scott, 1994).

1.3.5. Rickettsia species:

Rickettsai species (causing typhus fever) and coxiella burnetti are rarely isolated from the blood and in that case serological tests may be helpful in the diagnosis. Animal inoculation techniques may be necessary (Bailey and Scott, 1994).

1.3.6. Mycoplasma species:

The isolation of Mycoplasma hominis and ureaplasma urealyticum from blood has been repeatedly encountered in patient with post partum fever (Dalton and Nottebart, 1986).

1.3.7. Fungi:

The large size and sterol-containing cell walls of fungi make them particularly insensitive to the primary host defenses, antibody and phagocytic cells. Fungi in the blood stream can be carried to all organs of the host where they may grow, invade normal tissue and elaborate toxic products. Fungi gain enterance to the circulatory system via loss of integrity of the gastrointestinal tract or other organs or by means of intravascular catheters (Baily and Scott, 1994).

Those fungi include:

1- Candida albicans which is the most frequently isolated fungus from the blood cultures (vented broths containing glucose are desirable for the isolation of fungi) (Shanson, 1999).

2- Other Candida species include Cryptococcus neoformans, Histoplasma capsulatum and Aspergillus species which are rarely isolated from blood cultures (Shonson, 1999).

1.3.8. Viruses:

Arboviruses and viral causes of haemorrhagic fevers such as lassa fever virus ; animal inoculation techniques or suitable tissue cultures in designated reference laboratories are required (Shanson, 1999).

1.4. Predisposing factors for septicemia:

Factors predispose for septicemia are all listed in table (3) (Shanson, 1999).

Table. 1. Predisposing factors for septicaemia:

1. Impairment of general host defences

ii. Examples by treatment Immunosuppression

- Steroids

- Radiotoxic drugs

- Radiotherapy

- Severe neutropenia

- Cytotoxic drugs

i. Examples by disease

Diabetes mellitus.

Age extremes.

Premature babies

Very elderly




Hepatic failure

Leukaemia, reticulosis

Aplastic anaemia



Nephrotic syndrome

Congenital immunodeficiency

2. Instruonentation and surgery


surgery on the 4 urinary tract or large blowel

intravenous therapy central venous lines

urinary catheterization cytoscopy, trans-rectal prostatic biopsy

tracheostomy plus intermittent positive pressure ventilation and humidifiction

baby incubator and resuscitation equipment

radiological invasive techniques

3. factors that may encourage spread of spread of bacteria in hospital these include:

i. poor hospital hyginen and inadequate handwashing by staff between touching patients

ii. Aseptic technique lapes.

iii. Disinfectant policy not followed.

iv. Antibiotic overusage.

v. Isolation policy not practiced.

need to know how to diagnose? read lectures on applied clinical microbiology

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