Sepsis, Febrile Illness and Osteomyelitis - Lectures

Septicaemia, Febrile illness and Osteomyelitis Samuel Addo Akwetey Department of Clinical Microbiology SOM, UDS Sepsis A life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis and sep...

Septicaemia, Febrile illness and Osteomyelitis Samuel Addo Akwetey Department of Clinical Microbiology SOM, UDS Sepsis A life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis and septic shock cause approximately 250,000 deaths annually, have fatality rates of 30% to 50% in older patients. Sepsis continues to rise with the increased incidence of antibiotic- resistant organisms along with the increased use of immunosuppressive drugs, intravenous and urinary catheters, and prosthetic implants. Patients with sepsis can develop septic shock. Clinically, septic shock can be identified in septic patients who have persistent hypotension and elevated serum lactate. Pathophysiology Sepsis results from the interaction of the infectious agent, usually bacteria, with the: host’s immune, cardiovascular, neuronal, metabolic, and coagulation systems. Some degree of inflammatory response to infection is normal, but when this response is dysregulated, an excess of pro- and anti- inflammatory mediators leads to organ dysfunction. Sepsis caused by gram-positive bacteria is mediated by surface components such as peptidoglycan and teichoic acid. Some fungi, viruses, and protozoa have elements that can trigger macrophages to generate the same effect. Pathophysiology Sepsis is marked by an elevation in total blood leukocytes, especially neutrophils. It can be accompanied by a reduction in the number and function of leukocytes, particularly B and T lymphocytes. This limits the adaptive host response, enhances the severity of the infection. Sepsis occurs in the very young (neonatal sepsis), the very old, those with reduced host defenses, and people with chronic diseases such as diabetes, chronic Clinical Manifestation The clinical manifestations of sepsis often include fever and elevated neutrophils along with signs of organ system dysfunction, including hypoxemia, low platelets, abnormal liver function, hypotension, mental status changes, and kidney injury. Petechial hemorrhages and purpuric rash can occur as well, which indicate activation of the coagulation cascade. Pathogens Diagnosis Blood cultures are the mainstay of diagnosis of bloodstream infections. Urinalysis and urine cultures should also be done. Other sites of infection including skin lesions and sputum, should be cultured. Approximately 75% of septic patients will not have a causative organism identified by culture. Treatment It is essential to administer broad-spectrum bactericidal antibiotics intravenously to cover the most likely organisms. Antibiotics should be started directly after blood cultures are drawn. The prevalence of antibiotic-resistant organisms should be considered when choosing the antimicrobial drug regimen. One suggested antibiotic regimen includes vancomycin plus either a third- or fourth-generation cephalosporin such as ceftazidime or cefepime, piperacillin/tazobactam, or a carbapenem such as imipenem. An aminoglycoside or a fluoroquinolone can be added. None of these measures will be successful unless successful efforts are made to identify and remove the source of the infection. Prevention There are vaccines against N. meningitidis, S. pneumoniae, S. typhi, influenza virus, and yellow fever virus. Preventive antibiotics are given to those who develop immunosuppression and to pregnant women who test positive for group B Streptococcus carriage. Prompt removal of unnecessary intravenous and urinary catheters is important because these provide an entry point for bacteria and fungi into the bloodstream. Febrile illness Febrile illness Normal body temperature is maintained by a complex regulatory system in the anterior hypothalamus. Febrile illness is defined as a disease characterized by an increase of body temperature more than 37.5-Degree Celsius resulting from infectious process  Fahrenh Grade Celsius eit 36.6- Normal 37.2 98-99 Classification 37.2- of Fevers Low grade 37.8 99-100 37.8- Moderate 39.4 100-103 39.4- High grade 40.5 103-105 Hyperpyrexi  Usefulness of fever Allows the body to reach high temperature which can hinder some pathogens with strict temperature preference. Aids in host defense by: Increased proliferation of WBC Febrile Illness Enhanced leucocyte phagocytosis Decreased effects of endotoxin Increased generation of T-cells Enhanced activity of interferons  Metabolic effects of fever Increased need for oxygen, therefore there is raised heart rate and Febrile respiration. Illness Upsurge use of body proteins as energy source Body switches from the use of glucose to metabolism based on protein and fat breakdown  Febrile Illness Continuous fever Remittent fever Intermittent fever Temperature Temperature Temperature is remains above remains above present for some normal throughout normal throughout hours in a day and the day. the day but returns to normal Temp does not fluctuates more for the remaining fluctuate more than than 1 ◦C in 24hrs. time. 1◦C in 24hrs viral URTI, Malaria, Lobar pneumonia, legionella and septicaemia UTI, infective mycoplasma endocarditis, infections. typhoid. Febrile Illnes (Stages of fever) Prodrome - mild headache, fatigue, general malaise Temperature rise -Generalized shaking with chills -Vasoconstriction, onset of shivering, skin becomes pale. Flush -Cutaneous vasodilation, with skin becoming warm and flushed Defervescence -Initiation of sweating  Febrile Illness Bacterial diseases Viral disorders otitis media pharyngitis pharyngitis Rhinitis impetigo pneumonia bacterial meningitis relapsing fever typhoid fever typhus fever Febrile Illness Febrile diseases that are threats to the life of the victim include: malaria, typhoid fever, typhus fever, relapsing fever, shigellosis (Bacillary dysentery). Many febrile episodes are self-limited infections that in a normal host manifest with minimal signs of toxicity and require careful history and physical examination with few laboratory tests if any. However, there are well-defined high-risk groups that on the basis of age, associated diseases and immuno-deficiency require an extensive evaluation and in certain situations prompt antibiotic therapy before the pathogen is identified.  Aetiology of Febrile illness Common etiologies of Febrile Illness Borrelia recurrentis.………………………………………. Relapsing fever Salmonella typhi………………………………………….. Typhoid fever Rickettsia prowazeki……………………………………... Typhus fever Gram negative bacteria (E. coli, Pseudomonas )………. Pyelonephritis Plasmodium(malariae, ovale, falciparum, vivax)……..… Malaria Rhinovirus, adenovirus, Pneumococcus ….. Acute respiratory infection Shigella …………………………………………………….. Bacillary dysentery N. meningitidis……………………………………………… Meningitis Relapsing Fever Relapsing fever in epidemic form is caused by Borrelia recurrentis, which is transmitted by the human body louse pediculous humanis (the body louse). Endemic relapsing fever is caused by Borreliae transmitted by ticks called Ornithodoros. Whereas tick-borne relapsing fever is widespread in Africa, the louse-borne infection is largely limited to Ethiopia, Somalia and Sudan. The borreliae form irregular spirals 10–30 μm long and 0.3 μm wide. The organisms are highly flexible and move both by rotation and by twisting. Borreliae stain readily with bacteriologic dyes as well as with blood stains such as Giemsa stain or Wright stain. The organism can be cultured in fluid media containing blood, serum, or tissue. Multiplication is rapid in chick embryos when blood from patients is inoculated onto the chorioallantoic membrane. Sudden onset of high fever, often accompanied by chills, headache and muscle pain. Fever episodes can recur multiple times with asymptomatic periods in between. Relapsing Fever Antigenic Structure Antibodies develop in high titer after infection with borreliae. The antigenic structure of the organisms changes in the course of a single infection. The antibodies produced initially act as a selective factor that permits the survival only of antigenically distinct variants. The relapsing course of the disease appears to be caused by the multiplication of such antigenic variants, against which the host must then develop new antibodies. Ultimate recovery (after 3–10 relapses) is associated with the presence of antibodies against several antigenic variants. Relapsing Fever Fatal cases show spirochetes in great numbers in the spleen and liver, necrotic foci in other parenchymatous organs, and hemorrhagic lesions in the kidneys and the gastrointestinal tract. Spirochetes have occasionally been demonstrated in the spinal fluid and brain of persons who have had meningitis.  Relapsing Fever Pathogenesis and Clinical Findings The incubation period is 3–10 days. The onset is sudden, with chills and an abrupt rise of temperature. During this time, spirochetes abound in the blood. The fever persists for 3–5 days and then declines, leaving the patient weak but not ill. The afebrile period lasts 4–10 days and is followed by a second attack of chills, fever, intense headache, and malaise. There are 3–10 such recurrences, generally of diminishing severity. During the febrile stages (especially when the temperature is rising), organisms are present in the blood; during the afebrile periods, they are absent. Antibodies against the spirochetes appear during the febrile stage. Several distinct antigenic varieties of borreliae may be isolated from a single patient’s sequential relapses even after experimental inoculation with a single organism.  Relapsing Fever Diagnostic Laboratory Tests A. Specimens Blood specimens are obtained during the rise in fever for smears and animal inoculation. B. Smears Thin or thick blood smears stained with Wright or Giemsa stain reveal large, loosely coiled spirochetes among the red cells. C. Animal inoculation White mice or young rats are inoculated intraperitoneally with blood. Stained films of tail blood are examined for spirochetes 2–4 days later Treatment Tetracyclines, erythromycin, and penicillin are all believed to be effective.  Typhus Fever Louse-borne typhus is caused by Rickettsia prowazeki and is transmitted through the bite and feces of lice (pediculus humanus). Man is the only reservoir host. This form of typhus is, like relapsing fever, a classic example of an illness that is associated with war, malnutrition, crowding, and poor hygiene. Numerous local epidemics have been reported since the 1940s, especially in prisons, refugee camps, relief shelters, and rural villages. Changing and washing of clothes once a week reduces the density of lice significantly. Louse-borne typhus infections increase during the cool, rainy seasons, with persisting famine, political unrest, poor hygienic conditions, and crowded living conditions which are potential for large outbreaks. Flea-borne typhus is caused by Rickettsia typhi , which is transmitted from rats to man by a variety of lice, mites, and fleas, especially the rat flea (Xenopsylla cheopis).  Typhoid Fever The “Enteric Fevers” (Typhoid Fever) This syndrome is produced by only a few of the salmonellae, of which S. Typhi (typhoid fever) is the most important. The ingested salmonellae reach the small intestine, from which they enter the lymphatics and then the bloodstream. They are carried by the blood to many organs, including the intestine. The organisms multiply in intestinal lymphoid tissue and are excreted in stools. After an incubation period of 10–14 days, fever, malaise, headache, constipation, bradycardia, and myalgia occur. The fever rises to a high plateau, and the spleen and liver become enlarged. Rose spots, usually on the skin of the abdomen or chest, are seen briefly in rare cases. The white blood cell count is normal or low. The principal lesions are hyperplasia and necrosis of lymphoid tissue (eg, Peyer’s patches); hepatitis; focal necrosis of the liver; and inflammation of the gallbladder, periosteum, lungs, and other organs.  Typhoid Fever Diagnostic Laboratory Tests A. Specimens Blood for culture must be taken repeatedly. In enteric fevers and septicemias, blood culture results are often positive in the first week of the disease. Bone marrow cultures may be useful. Urine culture results may be positive after the second week. Stool specimens also must be taken repeatedly. In enteric fevers, the stools yield positive results from the second or third week on In enterocolitis, the stools yield positive results during the first week. A positive culture of duodenal drainage establishes the presence of salmonellae in the biliary tract in carriers.  CLINICAL FEATURES Most febrile illnesses have common type of clinical manifestations. This may make the accurate diagnosis of the cause of the fever difficult if not impossible. However, if thorough history and meticulous physical examination are done, it is possible to clinically differentiate the etiology of fever. Laboratory investigations also assist the clinical acumen in arriving at the diagnosis. Therefore, it is essential to have a very high index of suspicion of wider range of the etiologies and dig out the associated history and investigations thereof. Sometimes there could be a double infection (there could be two causes of fever). It is not uncommon to see a case of typhoid fever to have malaria in addition, a case of malaria presenting with cough etc.  CLINICAL FEATURES General Symptoms  Fever  Anorexia  General malaise and prostration  Myalgia and arthralgia  Chills  Rigors  Headache  Cough  Vomiting  Convulsion  CLINICAL FEATURES Signs Hepatomegaly Splenomegaly Rash Neck stiffness (Nuchal rigidity) Sensorial change DIAGNOSIS Clinical History Exposure to animals Geographic areas of living Travel history Dietary habits (raw or uncooked food) Contact with household pets Animal (insect) bite History of substance use (tobacco, marijuana) Family history of tuberculosis, febrile diseases, infectious diseases, collagen vascular diseases (arthritis) History of unusual familial symptomatology like deafness, urticaria, bone pain, anaemia DIAGNOSIS PHYSICAL EXAMINATION All vital signs are relevant. Temperature should be taken orally or rectally. Special attention be paid to the skin, lymph nodes, eyes, nail beds, cardiovascular system, chest, abdomen, musculoskeletal system, and CNS. The genitalia should be carefully examined in males and pelvic examination should be part of a complete physical examination in women. Pattern of fever should be followed carefully (sustained fever, intermittent fever, quotidian fever, relapsing fever, remittent fever).  DIAGNOSIS LABORATORY INVESTIGATION Laboratory data which will assist in ruling in or ruling out a diagnosis should be done. Blood (blood film, serological tests, widal reaction, weilfelix reaction, WBC and differential counts, ESR, blood sugar, hemoglobin) Cerebrospinal Fluid Stool Urine Bodily discharges (vaginal, urethral, lesion, etc). Radiological examination  Prevention and control of Acute Febrile Illnesses Personal hygiene food hygiene Avoid overcrowding (poor housing, poor ventilation) environmental hygiene. Osteomyelitis Osteomyelitis means infection of the bone. Osteo = bone myelo = bone marrow Incidence varies within countries More common in developing countries  Osteomyelitis (Risk factors) Non-hematogenous: Trauma Pressure ulcers Foreign body (prosthetics) Diabetes Peripheral vascular disease Peripheral neuropathy Hematogenous: Sickle cell anemia Diabetes IV drug use Indwelling catheters Immunodeficiency Endocarditis Pathogenesis Bacteremia or fungemia precedes osteomyelitis (hematogenous spread). Acute bacterial osteomyelitis often arises from a pyogenic skin infection such as a boil. Mycobacterial and fungal osteomyelitis often arise from the initial site of infection in the lung. It can also occur following trauma that results in an open fracture and direct contamination of the bone. In children, osteomyelitis occur at the end of long bones that are vascularised. In adults, hematogenous spread results most commonly in vertebral osteomyelitis and discitis. Chronic osteomyelitis tends to occur in the lower extremity, Clinical Manifestation Osteomyelitis is mainly characterized by bone pain and tenderness in the affected site. There are constitutive symptoms such as fever, night sweats and fatigue. Limited movements can be found in affected extremities whereas in vertebral osteomyelitis, the lumbar regions are mostly affected. In acute osteomyelitis, the symptoms occur abruptly and progress rapidly, whereas in chronic osteomyelitis, the course is more indolent. In chronic osteomyelitis, necrosis of the bone occurs, and a sequestrum can form at the site of the lesion. Relapses tend to occur in chronic osteomyelitis more than in acute osteomyelitis.  Osteomyelitis (Subtypes) Vertebral osteomyelitis: Most common subtype of osteomyelitis in adults. The lumbar spine is most commonly affected. Localized back pain: Radiation to the legs, abdomen, or groin. Worsens with activity and at night.  Osteomyelitis Sternoclavicular and Pelvic osteomyelitis Most frequent in IV drug users Sternoclavicular joint: Anterior chest wall swelling, pain, and tenderness May mimic a soft tissue abscess Pelvic osteomyelitis: Changes in gait or inability to bear weight Hip or buttock pain  Osteomyelitis Long bone osteomyelitis: Least common subtype in adults, but most common in children Can present similar to septic arthritis of a joint Weight bearing on affected long bones may be difficult. “Sausage toes” - a clinical sign that has been shown to have good sensitivity and specificity, may be present if osteomyelitis affects the phalanges of the feet in diabetic individuals Pathogens Diagnosis A microbiologic diagnosis of acute osteomyelitis is most consistently made by culture of a specimen of the bone lesion. Blood cultures are insensitive. Magnetic resonance imaging (MRI) scans in acute osteomyelitis shows a defect in the bone accompanied by periosteal elevation. Early in the disease, X-rays and even computed tomography (CT) scans may be negative. Treatment Vancomycin, nafcillin, or cephalexin administered parenterally can be used. Vancomycin is often used until the culture results and the sensitivity of the organism are known. If methicillin-resistant S. aureus (MRSA) is the cause then vancomycin or daptomycin can be used. If gram-negative rods are the cause, then ceftriaxone, ceftazidime, or cefepime can be used. The duration of therapy ranges from 3 to 6 weeks or longer. Surgical debridement of chronic osteomyelitis lesions is often necessary