How Effective Are Antibiotics for Sepsis?

Septicemia refers to an acute systemic infection that occurs when pathogenic bacteria or conditional pathogens invade the blood circulation, grow and reproduce in the blood, and produce toxins. If the bacteria that invade the bloodstream are cleared by the body's defense function, when there is no obvious symptoms of toxemia, it is called bacteriemia. Septicemia with multiple abscesses and a longer course is called pyemia. If sepsis is not quickly controlled, it can progress from the primary infection to other parts of the body, causing metastatic abscesses. Abscesses can occur on the surface of the brain, causing meningitis, pericarditis on the envelope around the heart, pericarditis on the heart, endocarditis, and osteomyelitis in the bone marrow. Joints, causing joint pain or arthritis. Eventually, abscesses can form anywhere in the body due to accumulation of pus, and severe cases develop septic shock and migrating lesions.

Basic Information

English name: septicemia
Visiting department: Emergency Department, Infectious Disease Department
Multiple groups: Immunocompromised

Common causes: Staphylococcus aureus, E. coli, and Streptococcus pneumoniae infections
Common symptoms: Chills, high fever, bleeding from skin and mucous membranes

Causes of sepsis

Common pathogenic bacteria are Staphylococcus aureus, E. coli, Streptococcus pneumoniae or Klebsiella pneumoniae. Staphylococcus epidermidis can be the pathogenic bacteria in children and those with low immune function.

Whether the bacteria invading the human body can cause sepsis is closely related to the virulence and quantity of invasive bacteria and the defense and immune function of the human body.

The following may lead to the occurrence of sepsis: skin and mucosal damage and wound infections, large-scale burns, open fractures, scabies, palate, infectious diarrhea, purulent peritonitis; various chronic diseases such as malnutrition, blood diseases ( Especially those with leukocyte deficiency), nephrotic syndrome, cirrhosis, diabetes, malignant tumors, reduced innate immunoglobulin synthesis, weakened leukocyte phagocytosis, etc., which can easily induce bacterial infections; various immunosuppressive drugs such as adrenal cortex hormones, anti-metabolism Drugs, anti-tumor drugs, and radiation therapy can weaken cellular immunity or humoral immunity, and some can reduce white blood cells or inhibit inflammatory reactions, which is conducive to the spread and spread of bacteria; long-term application of antibacterial drugs can easily cause drug-resistant strains to multiply and increase the chance of infection ; Various examinations or treatments plus endoscopy, intubation, saphenous vein intubation, indwelling urinary catheter, intravenous hypertrophic therapy, various dialysis, organ transplantation, etc. can cause bacteria to enter the blood circulation, or occur Infectious thrombosis and sepsis.

Changes of pathogenic bacteria and common septic pathogens: Various bacteria with pathogenic or conditional pathogenicity can become pathogens of sepsis. Due to different ages, different basic diseases of patients, different pathways and different ages, the bacteria causing sepsis are also different.

Clinical manifestations of sepsis

Sepsis itself has no special clinical manifestations. The symptoms seen during sepsis can also be seen in other acute infections, such as recurrent chills and even chills. The high fever can be a relaxation type or intermittent type, and the rash mainly consists of petechiae. Arthralgia involving large joints, mild hepatosplenomegaly, severe changes in consciousness, myocarditis, septic shock, disseminated intravascular coagulation (DIC), respiratory distress syndrome, etc., caused by various pathogenic bacteria Sepsis has its different clinical characteristics.

Staphylococcal septicemia

The primary lesions are often skin infections or wound infections. A small number of patients with nosocomial infections in the hospital have mostly pathogens in the blood from the respiratory tract. They are clinically acute, and their rashes are petechiae, urticaria, impetigo, and Scarlet fever-like rash and many other forms. The appearance of petechiae on the conjunctiva of the eye is of great significance. Symptoms of joints are obvious, sometimes redness and swelling, but suppuration is rare. Migration damage can occur in about 2/3 of patients. The most common are multiple pulmonary infiltration, abscess and pleurisy, followed by purulent meningitis, renal abscess, liver Abscesses, endocarditis, osteomyelitis, and subcutaneous abscesses. Septic shock occurs less frequently.

2. Staphylococcal sepsis

It is more common in hospital infections. When patients receive broad-spectrum antibiotics, the bacteria easily form resistant strains (methicillin-resistant strains). The number of bacteria in the respiratory tract and intestine is significantly increased, which can lead to systemic infections. After interventional treatment, such as artificial joints, artificial valves, pacemakers, and various catheters.

3. Enterococcal sepsis

Enterococcus is an opportunistic infection, usually parasitic in the intestine and urinary system. Its incidence has increased in the past 30 years. The most common clinical manifestations are urinary tract infections and endocarditis. Meningitis can also be seen , Osteomyelitis, pneumonia, enteritis and skin and soft tissue infections.

4. Gram-negative bacillus sepsis

Gram-negative bacillus sepsis can cause complex and diverse manifestations because different pathogens enter the blood through different pathways. Sometimes these manifestations are masked by the symptoms and signs of the primary disease. The pre-ill health is poor, and most of them are associated with affecting the body. Primary disease of defense function. There are many people infected in the hospital, chills, high fever, sweating, and bimodal fever are more common, and occasionally there are three-peak fever. This phenomenon is rare in sepsis caused by other bacteria, and it is worthy of attention. Septicemia caused by Escherichia coli, Alcaligenes, etc. can also have a fever-like fever type with relative pulse slowness. A few patients may not have a temperature rise, and rash, joint pain, and migrating lesions are less common than Gram-positive bulbar sepsis. However, the clinical manifestations of Pseudomonas aeruginosa sepsis secondary to malignant tumors are more dangerous. About 40% of Gram-negative bacillus sepsis patients can develop septic shock, and those with hypoalbuminemia are more likely to occur. In severe cases, multiple organ dysfunction may occur, including arrhythmia and heart failure; jaundice, liver failure; acute renal failure, respiratory distress and DIC.

5. Anaerobic septicemia

80% to 90% of its pathogenic bacteria are fragile bacilli, in addition to anaerobic streptococcus, pneumococcus, and perfringens, etc. The invasion route is mainly gastrointestinal and female reproductive tract, followed by bedsores and ulcer The clinical manifestations are similar to aerobic septicemia, and their characteristic manifestations are:

(1) The incidence of jaundice is as high as 10% to 40%, which may be related to the hemolytic effect of endotoxin of bacillus-like bacteria acting directly on the liver and a toxin of perfringens;

(2) The secretion of local lesions has a special rotten smell;

(3) easy to cause septic thrombophlebitis and migrating lesions in the thoracic cavity, lungs, endocardium, abdominal cavity, liver, brain and bones and joints, which are more common in septicemia of fragile bacteria and anaerobic streptococci;

(4) Severe hemolytic anemia and renal failure may occur in the septicemia of Percobacterium perfringens, gas is formed in the local migrating lesions, and anaerobic bacteria often together with aerobic bacteria cause multiple bacterial sepsis, with a dangerous prognosis.

6. Fungal sepsis

It usually occurs later in the course of severe primary diseases, often in chronic patients with liver disease, kidney disease, diabetes, blood disease or malignant tumors, or patients with severe burns, heart surgery, organ transplants, and more often with broad-spectrum antibiotics. Due to the history of adrenocortical hormones and / or antitumor drugs, almost all patients are those with low defense function, and the incidence has increased in recent years. The clinical manifestations of fungal sepsis are roughly the same as other sepsis, and most of them are accompanied by bacterial infections. Therefore, the symptoms of toxemia are often masked by coexisting bacterial infections or primary symptoms, and it is not easy to diagnose early.

Therefore, when the infection of the above patients does not improve after applying a sufficient amount of appropriate antibiotics, the possibility of fungal infection must be considered. For fungal culture of blood, urine, throat swabs and sputum, sputum can also be directly smeared for fungal mycelia and spores. If the same fungal result is obtained in multiple or multiple specimens, then The pathogen can be identified. The lesions can affect the organs and tissues of the heart, lungs, liver, spleen, and brain, forming multiple small abscesses, and they can be complicated by endocarditis and meningitis.

7. Septic shock

Septic shock is caused by toxins, cytokines, etc. produced by a specific bacterium, causing the patient's blood pressure to drop to low life-threatening levels. Septic shock is common in newborns, people over the age of 50, and people with impaired immune function. Septicemia is more dangerous if it occurs in patients with low white blood cell counts, such as cancer patients, patients undergoing anti-cancer chemotherapy, and patients with chronic diseases such as diabetes or liver cirrhosis.

Blood pressure decreases after vasodilation during septic shock, although heart rate increases and cardiac rejection increases at this time. The blood vessels can also increase the permeability, so that the liquid components in the blood stream leak into the tissue and cause edema. Reduced blood flow to important organs of the body, especially the kidneys and brain. Finally, blood vessels constrict in an attempt to raise blood pressure, but blood pressure remains low due to a decrease in the amount of blood pumped by the heart.

The initial indications of septic shock, even more than 24 hours before the drop in blood pressure, are changes in mental state and disorders, which are caused by reduced blood flow in the brain. The volume of blood discharged from the heart increases, but the blood pressure decreases due to vasodilation. Patients often have faster breathing, which causes them to exhale more carbon dioxide and reduce the amount of carbon dioxide in their blood. Early symptoms include chills, rapid rise in body temperature, flushed skin, and decreased urine output despite increased blood output. In the later stages, body temperature often drops below normal. Further worsening shock can lead to the failure of various organs, including the kidneys (showing low urine output), the lungs (showing dyspnea and decreased blood oxygen content), and the heart (showing fluid retention and edema), which can form coagulation processes in blood vessels.

Blood tests revealed increased or decreased white blood cells and decreased platelet counts. Levels of metabolically expendable products in the blood (such as urea nitrogen) continue to increase during renal failure. An electrocardiogram shows arrhythmia, indicating an insufficient blood supply to the heart muscle. Blood cultures can identify infected bacteria.

Sepsis test

Blood image

The total number of white blood cells mostly increased significantly, reaching (10-30) × 10 ⁹ / L, and the percentage of neutrophils increased, more than 80%, with obvious nuclear left shift and intracellular poisoning particles. A small number of patients with Gram-negative sepsis and reduced immune function may have normal or slightly reduced white blood cells.

2. Neutrophil tetrazole nitrogen blue (NBT) test

This test is positive only for bacterial infections, and can be as high as 20% (normally below 8%), which is helpful for distinguishing viral infections and non-infectious diseases from bacterial infections.

3. Septicemia 3. Etiology

Blood and bone marrow cultures are positive. If the bacteria are the same as those obtained from the culture of local lesions (pus, urine, pleural fluid, cerebrospinal fluid, etc.), the diagnosis can be more confirmed.

Diagnosis of sepsis

Because the majority of sepsis is secondary to various infections and lacks specific clinical manifestations, it is easy to cause missed diagnosis or misdiagnosis. In order to improve the early diagnosis rate of sepsis, corresponding examinations should be performed in time.

Elevated white blood cells and neutrophils, recent respiratory, digestive, urinary tract infections or burns, device operation history, and various focal infections that have not been effectively controlled despite antibacterial treatment should be highly suspected. Septicemia is possible. Blood culture is the most reliable diagnosis of sepsis. Negative blood culture and positive bone marrow culture have the same meaning as positive blood culture. Other cultures such as sputum, urine, pleural effusion, ascites, purulent secretions, etc. are of reference significance for clear diagnosis. Examination of blood, urine, pleural and ascites fluids for endotoxins to confirm gram-negative bacterial infection. In the course of the disease, petechiae such as ocular conjunctiva, oral mucosa, rash, liver and spleen, migration damage or abscess appear, and the diagnosis of sepsis can be basically established.

Differential diagnosis of sepsis

It is distinguished from miliary tuberculosis, malignant histiocytosis, systemic lupus erythematosus, deep lymphoma, allergic subsepticemia, brucellosis, typhoid fever, epidemic hemorrhagic fever, malaria, rheumatism, etc.

Complications of sepsis

Staphylococcus aureus can be complicated by septic shock, kidney, liver abscess, gram-negative bacillus sepsis, and heart failure; jaundice, liver failure; acute renal failure, respiratory distress, and DIC. S. sepsis can cause severe hemolytic anemia and renal failure, and can be complicated by endocarditis and meningitis.

Septicemia treatment

1. Basic treatment and symptomatic treatment

Patients with sepsis have poor constitution, severe symptoms, and the condition needs to continue for a period of time. Therefore, while applying special antibacterial treatment, attention should be paid to supplement various vitamins, energy mixtures, and even small amounts of human albumin (albumin), Plasma or fresh whole blood supplements the body's consumption, supplies energy, strengthens nutrition, supports organ function, timely corrects water and electrolyte disorders, maintains acid-base balance, and maintains internal environment stability. In the presence of severe toxemia such as shock and toxic myocarditis, booster drugs, cardiotonic drugs and / or short-range adrenocortical hormones can be given. Antipyretics and sedative pain can be given to those with severe fever, severe headache and irritability. Intensive care is needed to prevent secondary stomatitis, pneumonia, urinary infections, and pressure ulcers.

2. Antibacterial treatment

When septicemia is suspected, the selection of targeted antibacterial drugs is the key to successful treatment. It is best to keep blood for culture before the application of antibacterial drugs.

(1) Application principle of antibacterial drugs Targeted application The timely application of highly targeted antibacterial drugs is the key to the treatment of sepsis, and it should be adjusted based on clinical manifestations and early treatment response. Combined medication For critically ill patients, two antibiotics should be selected for combined application (the necessity of triple or quadruple application is not great). A sufficient amount of foot treatment should be used to kill pathogens, not to inhibit them for a while. Therefore, the use of antibacterial drugs should be sufficient, and the dose should be large at the beginning. It should be administered by intravenous drip, and the effect should be long, usually more than 3 weeks. Or, after the body temperature is normal and the symptoms disappear, continue to take the medicine for several days. For patients with migratory lesions, in addition to local treatment, systemic medication should be extended as appropriate.

(2) Selection of antibacterial drugs Staphylococcal septicemia Because Staphylococcus aureus can produce -lactamase strains of about 90%, penicillin G is very poor in its efficacy. The first and second-generation cephalosporins inhibited the -lactamase effect to varying degrees, and the strains that are sensitive to it can reach 90%. Therefore, cefazolin, cephalexin, cefuroxime, or cefaclor are often used. You can also choose fluoroquinolones for treatment. You can also use amikacin and gentamicin in combination. Vancomycin is generally preferred for methicillin-resistant Staphylococcus aureus. Alternative drugs include linezolid, daptomycin, and tigecycline. Gram-negative bacillus sepsis The third-generation cephalosporins have strong antibacterial activity against such bacteria, and the sensitivity rate is generally greater than 90%. The second-generation cephalosporins also have antibacterial activity against E. coli and pneumococci. Therefore, for this type of sepsis, one can be selected from the second and third generation cephalosporins, which can be combined with gentamicin or amikacin. For Pseudomonas aeruginosa sepsis, piperacillin / tazobactam, cefoperazone / sulbactam, ceftazidime, cefepime or carbapenems are preferred. Or use the medicine with aminoglycoside antibiotics, the effect is also good. Quinolones such as levofloxacin and ciprofloxacin have strong antibacterial activity against G-bacteria, including Pseudomonas aeruginosa, and are less affected by the outside world. They have no cross-resistance with other antibacterial drugs and have mild side effects. It is often used clinically. Anaerobic septicemia is often a mixed infection of multiple bacteria. When selecting a drug, facultative anaerobic or aerobic bacteria should be considered. Fungal septicemia When fungi and bacterial infections coexist, drug selection must be considered.

3. Other treatments

(1) Drugs such as anti-endotoxin monoclonal antibodies, interleukin-1 (IL-1) receptor antagonists, deglycoside deaminase inhibitors, etc.

(2) Local treatment For primary or migrating suppurative lesions, incision and drainage should be performed in time after they mature. After purulent pericarditis, arthritis, empyema, and liver abscesses, antibacterial drugs can be injected locally after drainage. For obstructed biliary and urinary tract infections, surgery should be considered to remove the obstruction.

(3) Treatment of basic diseases