Is systemic inflammatory response (SIR) to infection (Rackow EC., 1986). It represents progressive stages of the same illness in which a systemic response to an infection mediated by endogenous mediators may lead to a generalized inflammatory reaction in organs remote from the initial insult and eventually to end organ dysfunction and /or failure (Bone RB, et al., 1998). Sepsis remains an important and life-threatening problem as it is the most common cause of death in the intensive care unit (Parrillo JE, et al., 1990). Also it is possible that many deaths due to sepsis are attributed to underlying diseases when mortality statistics are complied (Young, L.s., 1990).
The use of the term sepsis is not restricted to a systemic inflammatory syndrome secondary to bacterial infection, but to this syndrome resulting from any microorganisms and/ or its products (toxins). The term sepsis is applicable only when the systemic response is clinically relevant, which can manifest in a variety of situations of increasing complexity such as : (a) severe sepsis, understood as sepsis associated with organ failure, hypoperfusion (which includes, but is not limited to lactic acidosis, oliguria or an acutely altered state of consciousness) and hypotension; (b) septic shock, understood as sepsis associated with hypoperfusion alterations, but with persistent hypotension even after suitable volumetric resuscitation, and (c) multiple organ failure syndrome (MOFS), which may represent the final stage of the sever systemic inflammatory response. However, the limits which separate sepsis from severe sepsis and this from septic shock are not easily detected in clinical at ICUs, or
even from a conceptual point of view. (Levy MM, et al, 2003; Despond O, et al, 2001).
Diagnosis of sepsis
Diagnosis of sepsis is based on a high level of suspicion, which demands a minutely detailed collection of information on present status and medical history of the patient, a good clinical evaluation, certain laboratory tests, in addition to rigorous clinical monitoring of the patient. There are three key difficulties associated with the diagnosis of infection in patients who have sepsis: і) establishing infection as the primary cause which is the first important step in the diagnosis, this will exclude non-infective causes of SIRS ((M.LIewelyn, et al., 2001). іі) localizing the site of infection: The identification of the primary site of infection is a critical part of the work-up of the septic patient. Together with the gram stain of specimens obtained from any site suspected of infection, it is probably the single most important information in guiding the choice of antibiotic therapy (Sands KE, et al., 1997; Boillot A, et al., 1995; Bernard GR, et al., 1997). ііі) interpreting the microbiological findings (M.LIewelyn, et al., 2001).
The International Sepsis Definitions Conference amplified the list of possible clinical and laboratory signs of sepsis which may allow for more efficacious suspicion and management. (Paulo R, et al., 2003). The symptoms and signs that should lead to suspect sepsis are as follow:
General variables:
- Fever (core temperature > 38.3 °C)
- Hypothermia (core temperature < 36 °C)
- Heart rate > 90 min-1 or > 2 SD above the normal value for age
- Tachypnea
- Altered mental status
- Significant edema or positive fluid balance (> 20 ml/kg over 24 hrs)
- Hyperglycemia (plasma glucose > 120 mg/dl or 7.7 mmol/l) in the absence of diabetes
Inflammatory variables:
- Leukocytosis ( WBC count >12,000/mm3)
- Leukopenia (WBC count < 4,000/ mm3)
- Normal WBC count with > 10 % immature forms
- Plasma C- reactive protein > 2 SD above the normal value
- Plasma procalcitonin > 2 SD above the normal value
Hemodynamic variables:
- Arterial hypotension (SBP < 90 mm Hg, MAP < 70, or an SBP decrease > 40 mm Hg in adults or <2 SD below normal for age)
- Mixed venous oxygen saturation SvO2 > 70 %
- Cardiac index > 3.5 1/min-1/M -23
Organ dysfunction variables:
- Arterial hypoxemia (PaO2/FIO2< 300)
- Acute oliguria (urine output < 0.5 ml/kg -1/hr -1 or 45 mmol/1 for at least 2 hrs)
- Creatinine increase > 0.5 mg/dl
- Coagulation abnormalities ( INR >1.5 or aPTT > 60 secs)
- Ileus (absent bowel sounds)
- Thrombocytopenia (platelet count < 100,000/mm3)
- Hyperbilirubinemia (plasma total bilirubin > 4 mg/dl or 70 mmol/l)
Tissue perfusion variables:
- hyperlactatemia (>1 mmol/l)
- Decreased capillary refill or mottling
(Levy MM, et al., 2003)
Causative organisms:
Sepsis and septic shock, caused by gram-negative, gram positive bacteria, fungi, viruses, and parasites, have become increasingly important over the past decades (Glauser, et al., 1991). In the United States, the septicemia rates more than doubled between 1979 and 1987 causing up to 250,000 deaths annually (Opal, et al., 1999 ; Parillo, et al., 1993). The proportion of infections due to gram-negative bacteria varied between 30 and 80% and that of infections due to gram-positive bacteria varied between 6 and 24% of the total number of cases of sepsis, with the remainder being accounted for by other pathogenic organisms (Glauser, et al., 1991).
Gram-negative sepsis
Was a relatively rare clinical diagnosis only a few decades ago, but today it is the most important infectious disease problem in hospitals. Nearly 80 % of all documented epidemics were caused by gram-negative bacilli. ( Roger C and Bone ., 1993). Estimated mortality from sepsis of gram-negative etiology ranges from 20 to 50 % of the overall total number of septic death. (Wenzel, R. P., 1988; Young, L. S., 1990).
Most gram negative infections were caused by Enterobacteriaceae with Escherichia coli which is the most commonly isolated pathogen, followed by klebseilla and enterobacter species. Although pseudomonas species were encountered somewhat less frequently, pseudomonas aeruginosa has consistently been associated with the highest mortality rate among all causes of bacteremic infection. (Young, L. S., 1990)
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Showing posts with label sepsis. Show all posts
Showing posts with label sepsis. Show all posts
Saturday, October 29, 2011
Friday, August 26, 2011
Sepsis, bacteremia and septicemia
There have been several attempts to define sepsis. The various definitions which exist to describe sepsis demonstrate the complexities of the septic process. In general, sepsis can be defined as the systemic host response to infection. It is usually associated with several signs, which include: fever, increased C-reactive protein (CRP), increased heart rate and cardiac output, tachypnea, and increased oxygen consumption among others. However, these may not occur in all patients. Bacteremia can be defined as the presence of viable bacteria in the blood and septicemia is the association of bacteremia with sepsis. Severe sepsis is usually associated with organ dysnfuction, alterations in mental status, coagulation dysfunction and hypoxemia (Vincent, 2002).
Regardless of the definitions used, there is no doubt of the magnitude of the problem, with sepsis affecting some 2-14% of intensive care unit (ICU) admissions, with mortality rates of 35-50%. Aside from the high levels of morbidity and mortality, sepsis is also associated with increased hospital and ICU stays, expensive antimicrobial therapies, and prolonged duration of mechanical ventilation, which all represent a serious economic burden (Vincent, 2002).
The most common isolates in infections causing sepsis are in descending order S.aureus, coagulase-negative Staphylococci, Pseudomonas aeruginosa, Enterobacter, Klebsiella, Acinetobacter, Serratia and Candida (Vincent, 2002). It is thus apparent that Gram-positive organisms can be considered the most important etiological factors for septicemia.
The prognosis of septic patients is influenced not only by the severity of infection, but also by the previous health status and the host response (degree of immunocompetence)(Vincent, 2002). In general, logistic regression or Cox modeling techniques are used to identify those clinical factors that are independently associated with the probability of death (Wax et al., 2002).
Sepsis is a also major health problem in children with high mortality rates. Neonates in particular are at highest risk, especially those with low birth weights. Staphylococci are the most common causes of sepsis in children as well, and are associated with considerable mortality rates (Watson et al., 2003).
Regardless of the definitions used, there is no doubt of the magnitude of the problem, with sepsis affecting some 2-14% of intensive care unit (ICU) admissions, with mortality rates of 35-50%. Aside from the high levels of morbidity and mortality, sepsis is also associated with increased hospital and ICU stays, expensive antimicrobial therapies, and prolonged duration of mechanical ventilation, which all represent a serious economic burden (Vincent, 2002).
The most common isolates in infections causing sepsis are in descending order S.aureus, coagulase-negative Staphylococci, Pseudomonas aeruginosa, Enterobacter, Klebsiella, Acinetobacter, Serratia and Candida (Vincent, 2002). It is thus apparent that Gram-positive organisms can be considered the most important etiological factors for septicemia.
The prognosis of septic patients is influenced not only by the severity of infection, but also by the previous health status and the host response (degree of immunocompetence)(Vincent, 2002). In general, logistic regression or Cox modeling techniques are used to identify those clinical factors that are independently associated with the probability of death (Wax et al., 2002).
Sepsis is a also major health problem in children with high mortality rates. Neonates in particular are at highest risk, especially those with low birth weights. Staphylococci are the most common causes of sepsis in children as well, and are associated with considerable mortality rates (Watson et al., 2003).
Sepsis, bacteremia and septicemia
There have been several attempts to define sepsis. The various definitions which exist to describe sepsis demonstrate the complexities of the septic process. In general, sepsis can be defined as the systemic host response to infection. It is usually associated with several signs, which include: fever, increased C-reactive protein (CRP), increased heart rate and cardiac output, tachypnea, and increased oxygen consumption among others. However, these may not occur in all patients. Bacteremia can be defined as the presence of viable bacteria in the blood and septicemia is the association of bacteremia with sepsis. Severe sepsis is usually associated with organ dysnfuction, alterations in mental status, coagulation dysfunction and hypoxemia (Vincent, 2002).
Regardless of the definitions used, there is no doubt of the magnitude of the problem, with sepsis affecting some 2-14% of intensive care unit (ICU) admissions, with mortality rates of 35-50%. Aside from the high levels of morbidity and mortality, sepsis is also associated with increased hospital and ICU stays, expensive antimicrobial therapies, and prolonged duration of mechanical ventilation, which all represent a serious economic burden (Vincent, 2002).
The most common isolates in infections causing sepsis are in descending order S.aureus, coagulase-negative Staphylococci, Pseudomonas aeruginosa, Enterobacter, Klebsiella, Acinetobacter, Serratia and Candida (Vincent, 2002). It is thus apparent that Gram-positive organisms can be considered the most important etiological factors for septicemia.
The prognosis of septic patients is influenced not only by the severity of infection, but also by the previous health status and the host response (degree of immunocompetence)(Vincent, 2002). In general, logistic regression or Cox modeling techniques are used to identify those clinical factors that are independently associated with the probability of death (Wax et al., 2002).
Sepsis is a also major health problem in children with high mortality rates. Neonates in particular are at highest risk, especially those with low birth weights. Staphylococci are the most common causes of sepsis in children as well, and are associated with considerable mortality rates (Watson et al., 2003).
Regardless of the definitions used, there is no doubt of the magnitude of the problem, with sepsis affecting some 2-14% of intensive care unit (ICU) admissions, with mortality rates of 35-50%. Aside from the high levels of morbidity and mortality, sepsis is also associated with increased hospital and ICU stays, expensive antimicrobial therapies, and prolonged duration of mechanical ventilation, which all represent a serious economic burden (Vincent, 2002).
The most common isolates in infections causing sepsis are in descending order S.aureus, coagulase-negative Staphylococci, Pseudomonas aeruginosa, Enterobacter, Klebsiella, Acinetobacter, Serratia and Candida (Vincent, 2002). It is thus apparent that Gram-positive organisms can be considered the most important etiological factors for septicemia.
The prognosis of septic patients is influenced not only by the severity of infection, but also by the previous health status and the host response (degree of immunocompetence)(Vincent, 2002). In general, logistic regression or Cox modeling techniques are used to identify those clinical factors that are independently associated with the probability of death (Wax et al., 2002).
Sepsis is a also major health problem in children with high mortality rates. Neonates in particular are at highest risk, especially those with low birth weights. Staphylococci are the most common causes of sepsis in children as well, and are associated with considerable mortality rates (Watson et al., 2003).
Wednesday, July 27, 2011
Sepsis in Children with Oncohematological Malignancies, old Problem Revisited
Though the use of aggressive treatment protocols that combine chemotherapy, radiation, and surgery, the prognosis for patients with childhood malignancies has improved substantially. However, these intensive treatment regimens can cause life-threatening complications, the
most prominent of which are infections that result from treatment-associated immunosuppression.
Historically, sepsis and septic shock in pediatric oncology patients have carried a poor prognosis. Earlier studies, however, used a variety of criteria to define sepsis and septic shock, and most included relatively small numbers of children. Some studies even excluded patients who had received bone marrow transplants (BMT).
Sepsis is a leading cause of death in critically ill patients despite the use of modern antibiotics and resuscitation therapies. The septic response is an extremely complex chain of events involving inflammatory and anti-inflammatory processes, humoral and cellular reactions and circulatory abnormalities. The diagnosis of sepsis and evaluation of its severity is complicated by the highly variable and non-specific nature of the signs and symptoms of sepsis. However, the early diagnosis and stratification of the severity of sepsis is very important, increasing the possibility of starting timely and specific treatment.
A rapid microbiological diagnosis could therefore confirm an infectious cause of fever and aid in the choice of a specific therapy. Among the infectious causes, bacteria and fungi are the leading threats, with high infection-related mortality rate, especially for polymicrobial infections and moulds. The current gold standard for the detection of bacterial pathogens in blood is blood culture. However, all blood culture systems suffer from several limitations, such as lack of rapidity and low sensitivity, especially when the patient has already received antibiotics and when fastidious micro-organisms are involved. From this perspective, the diagnosis of bloodstream infections could prove really challenging in oncohaematological patients, who routinely receive prophylactic antibiotics and whose blood cultures therefore often remain negative. Even after the detection of growth in cultured blood (usually not before 6–12 h of incubation), conventional blood cultures require at least a further 24–48 h for the definitive identification of the pathogen and the evaluation of its sensitivity to antibiotics. Other parallel approaches are therefore needed, and among them well-designed molecular assays could prove really useful. Several molecular techniques have already been successfully used in routine microbiology laboratories for direct detection of viral, bacterial, mycotic and protozoan pathogens. However, their use on whole blood samples for detection of sepsis has been hampered by several factors, including insufficient sensitivity, presence of PCR inhibitors in blood, and the difficulty of setting up an assay capable of detecting a wide range of potential pathogens.
Another advance in diagnosis of sepsis is the use of biomarkers. Biomarkers can have an important place in this process because they can indicate the presence or absence or severity of sepsis. A biomarker is defined as ‘‘a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.’’.
Beside rapid diagnosis of sepsis, other potential uses of biomarkers include roles in prognostication, guiding antibiotic therapy, evaluating the response to therapy and recovery from sepsis, differentiating Gram-positive from Gram-negative microorganisms as the cause of sepsis, predicting sepsis complications and the development of organ dysfunction (heart, kidneys, liver or multiple organ dysfunction). However, the exact role of biomarkers in the management of septic patients remains undefined. C-reactive protein (CRP) has been used for many years but its specificity has been challenged. Procalcitonin (PCT) has been proposed as a more specific and better prognostic marker than CRP, although its value has also been challenged. It remains difficult to differentiate sepsis from other non-infectious causes of systemic inflammatory response syndrome, and there is a continuous search for better biomarkers of sepsis.
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Wednesday, June 15, 2011
Sepsis
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).
NO OBVIOUS LOCALIZED SEPSIS
e.g.,Gram-negative bacilli invade blood from a site with normal flora, such as the gut
SURGERY OR INSTRUMENTATION
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.
PRE-EXISTING LOCALIZED SEPSIS
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
Debilitation
Malignancy
Uraemia
Hepatic failure
Leukaemia, reticulosis
Aplastic anaemia
Myeloma
Malabsorption
Nephrotic syndrome
Congenital immunodeficiency
2. Instruonentation and surgery
examples:
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.
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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).
NO OBVIOUS LOCALIZED SEPSIS
e.g.,Gram-negative bacilli invade blood from a site with normal flora, such as the gut
SURGERY OR INSTRUMENTATION
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.
PRE-EXISTING LOCALIZED SEPSIS
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
Debilitation
Malignancy
Uraemia
Hepatic failure
Leukaemia, reticulosis
Aplastic anaemia
Myeloma
Malabsorption
Nephrotic syndrome
Congenital immunodeficiency
2. Instruonentation and surgery
examples:
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.
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