Sepsis. Treatment. Empiric therapy for sepsis

Microbiological diagnosis of sepsis.

Based on microbiological (bacteriological) examination of peripheral blood and material from the alleged focus of infection. When isolating typical pathogens (Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, fungi), one positive result is sufficient to make a diagnosis; if MBs are isolated that are skin saprophytes and can contaminate the sample (Staphylococcus epidermidis, other coagulase-negative staphylococci, diphtheroids), two positive blood cultures are required to confirm true bacteremia.

The diagnosis of sepsis should be considered proven if the same microorganism is isolated from the suspected site of infection and from the peripheral blood and there are signs of SIRS. If a microorganism is isolated from the blood, but there are no signs of SIRS, bacteremia is transient and is not sepsis.

Basic requirements for microbiological blood testing:

1. Blood for research must be taken before the appointment of AB; if the patient is already receiving ABT, blood should be taken immediately before the next administration of the drug

2. The standard for blood testing for sterility - sampling from two peripheral veins with an interval of up to 30 minutes, while blood must be taken from each vein in two vials (with media for the isolation of aerobes and anaerobes); if fungal etiology is suspected, special media should be used to isolate fungi.

3. Blood for research must be taken from a peripheral vein. Blood sampling from the catheter is not allowed (except in cases of suspected catheter-associated sepsis).

4. Blood sampling from a peripheral vein should be carried out with careful observance of asepsis: the skin at the venipuncture site is treated twice with a solution of iodine or povidone-iodine with concentric movements from the center to the periphery for at least 1 minute, immediately before sampling, the skin is treated with 70% alcohol. When performing venipuncture, the operator uses sterile gloves and a sterile dry syringe. Each sample (about 10 ml of blood or the volume recommended by the vial manufacturer's instructions) is withdrawn into a separate syringe. The lid of each vial with the medium is treated with alcohol before piercing with a needle to inoculate blood from a syringe.

NB! Absence of bacteremia does not rule out sepsis, because even with the most scrupulous observance of the technique of blood sampling and the use of modern microbiological technologies in the most severe patients, the frequency of detection of bacteremia does not exceed 45%.

To make a diagnosis of sepsis, it is also necessary to carry out the necessary laboratory and instrumental studies to assess the state of a number of organs and systems (according to the classification of sepsis - see question 223), to assess the overall severity of the patient's condition on the A. Baue, SOFA, APACHE II, SAPS-II scales.

Basic principles of sepsis therapy:

1. Complete surgical sanitation of the focus of infection- without eliminating the focus of infection, intensive measures do not lead to a significant improvement in the patient's condition; when a source of infection is found, it should be drained as much as possible, according to indications, necrectomy should be performed, internal sources of contamination should be removed, perforations of hollow organs should be eliminated, etc.

2. Rational antibiotic therapy- can be empirical and etiotropic; in the case of an unidentified focus of infection, antibiotics of the widest spectrum of action should be used.

Principles of antibiotic therapy:

Antibiotic therapy for sepsis should be prescribed immediately after the nosological diagnosis has been clarified and until the results of a bacteriological study are obtained (empirical therapy); after receiving the results of a bacteriological study, the ABT regimen can be changed taking into account the isolated microflora and its antibiotic sensitivity (etiotropic therapy)

At the stage of empirical ABT, it is necessary to use antibiotics with a wide spectrum of activity, and, if necessary, to combine them; the choice of a specific empirical ABT is based on:

a) the spectrum of suspected pathogens depending on the location of the primary focus

b) the level of resistance of nosocomial pathogens according to microbiological monitoring data

c) conditions for the occurrence of sepsis - out-of-hospital or nosocomial

d) the severity of the infection, assessed by the presence of multiple organ failure or the APACHE II scale

In community-acquired sepsis, drugs of choice are third-generation cephalosporins (cefotaxime, ceftriaxone) or fourth-generation fluoroquinolones (levofloxacin, moxifloxacin) + metronidazole; in nosocomial sepsis, drugs of choice are carbapenems (imipenem, meropenem) + vancomycin or linezolid + vancomycin.

When an etiologically significant microorganism is isolated from the blood or the primary focus of infection, it is necessary to carry out etiotropic antibiotic therapy (methicillin-sensitive staphylococcus - oxacillin or oxacillin + gentamicin, methicillin-resistant staphylococcus - vancomycin and / or linezolid, pneumococcus - cephalosporins of the III generation, if ineffective - vancomycin, enterobacteria - carbapenems, etc. .d., anaerobes - metronidazole or lincosamides: clindamycin, lincomycin, candida - amphotericin B, fluconazole, caspofungin)

ABT of sepsis is carried out until a stable positive dynamics of the patient's condition is achieved, the main symptoms of infection disappear, negative blood culture

3. Pathogenetic therapy of complicated sepsis:

a) hemodynamic support:

Hemodynamic monitoring is carried out invasively using a floating Swan-Ganz type catheter, which is inserted into the pulmonary artery and allows you to fully assess the state of blood circulation at the patient's bedside

Conducting infusion therapy using solutions of crystalloids and colloids in order to restore tissue perfusion and normalize cellular metabolism, correct hemostasis disorders, reduce mediators of the septic cascade and the level of toxic metabolites in the blood

Within the next 6 hours, you must achieve the following target values: CVP 8-12 mm Hg, BPmean> 65 mm Hg, diuresis 0.5 ml/kg/h, hematocrit> 30%, blood saturation in the superior vena cava 70%.

The volume of infusion therapy is selected strictly individually, taking into account the patient's condition. It is recommended to introduce 500-1000 ml of crystalloids (physical solution, Ringer solution, Normosol solution, etc.) or 300-500 ml of colloids (solutions of destrana, albumin, gelatinol) in the first 30 minutes of infusion therapy. , hydroxyethyl starches), evaluate the results (in terms of increased blood pressure and cardiac output) and tolerability of the infusion, and then repeat the infusions in an individual volume.

The introduction of drugs that correct the state of the blood: infusion of cryoplasma with coagulopathy of consumption, transfusion of donor erythrocyte mass with a decrease in hemoglobin level below 90-100 g/l

The use of vasopressors and drugs with a positive inotropic effect according to indications is indicated if the corresponding fluid load is not able to restore adequate blood pressure and organ perfusion, which should be monitored not only by the level of systemic pressure, but also by the presence of anaerobic metabolic products such as lactate in the blood, etc. .d. The drugs of choice for correcting hypotension in septic shock are norepinephrine and dopamine/dopamine 5–10 mcg/kg/min via a central catheter; the first line drug to increase cardiac output is dobutamine 15–20 mcg/kg/min IV

b) correction of acute respiratory failure (ARDS): respiratory support (IVL) with parameters that provide adequate ventilation of the lungs (PaO 2 > 60 mm Hg, PvO 2 35-45 mm Hg, SaO 2 > 93%, SvO 2 > 55%)

c) adequate nutritional support– necessary, because PON in sepsis is accompanied by hypermetabolism, in which the body covers its energy costs by digesting its own cellular structures, which leads to endotoxicosis and potentiates multiple organ failure.

The earlier nutritional support is started, the better the results, the method of nutrition is determined by the functional capacity of the gastrointestinal tract and the degree of nutritional deficiency.

Energy value - 25 - 35 kcal / kg / day in the acute phase and 35 - 50 kcal / kg / day in the phase of stable hypermetabolism

Glucose< 6 г/кг/сут, липиды 0,5 - 1 г/кг/сут, белки 1,2 – 2,0 г/кг/сут

Vitamins - standard daily set + vitamin K (10 mg/day) + vit B1 and B6 (100 mg/day) + vit A, C, E

Trace elements - standard daily set + Zn (15-20 mg / day + 10 mg / l in the presence of loose stools)

Electrolytes - Na + , K + , Ca2 + according to balance calculations and plasma concentration

d) hydrocortisone in small doses 240-300 mg / day for 5-7 days - accelerates the stabilization of hemodynamics and allows you to quickly cancel vascular support, indicated in the presence of signs of septic shock or adrenal insufficiency

e) anticoagulant therapy: activated protein C / zigris / drotrecogin-alpha - indirect anticoagulant, also has anti-inflammatory, antiplatelet and profibrinolytic effects; the use of activated protein C at a dose of 24 mcg / kg / hour in the first 96 hours of sepsis reduces the risk of death by about 20%

f) immunoreplacement therapy: pentaglobin (IgG + IgM) at a dose of 3-5 ml / kg / day for 3 days - limits the damaging effect of pro-inflammatory cytokines, increases the clearance of endotoxins, eliminates anergy, enhances the effects of beta-lactams. Intravenous administration of immunoglobulins is the only really proven method of immunocorrection in sepsis that increases survival.

g) prevention of deep vein thrombosis in long-term patients: heparin 5000 IU 2-3 times / day s / c for 7-10 days under the mandatory control of APTT or low molecular weight heparins

h) prevention of stress ulcers of the gastrointestinal tract: famotidine / quamatel 50 mg 3-4 times/day IV, omeprazole 20 mg 2 times/day IV

i) extracorporeal detoxification(hemodialysis, hemofiltration, plasmapheresis)

INTRODUCTION: Inadequate initial antibiotic therapy, defined as the lack of in vitro effect of an antimicrobial agent against an isolated pathogen responsible for the development of an infectious disease, is associated with increased morbidity and mortality in patients with neutropenic fever or severe sepsis. To reduce the likelihood of inappropriate antibiotic therapy, recent international guidelines for the treatment of sepsis have proposed empiric therapy targeting Gram-negative bacteria, especially when sepsis is suspected. pseudomonadic infection. However, the authors of this recommendation are aware that "there is no single study or meta-analysis that has convincingly demonstrated superior clinical outcome of combination therapy in a specific patient population for specific pathogens."

Theoretical basis for prescribing combination therapy:

• an increase in the likelihood that at least one drug will be active against the pathogen;
• prevention of persistent superinfection;
• immunomodulatory non-antibacterial effect of the secondary agent;
• enhancement of antimicrobial action based on synergistic activity.

Unlike patients with febrile neutropenia, which has been repeatedly and well studied, there have been no randomized trials of severe septic patients with increased capillary permeability syndrome and multiple organ failure, in which the distribution and metabolism of antibiotics may be impaired.

The main aim of this study was to compare the effectiveness of combination therapy with two broad-spectrum antibiotics moxifloxacin and meropenem with meropenem monotherapy in multiple organ failure caused by sepsis.

METHODS: A randomized, open, parallel group study was conducted. 600 patients with severe sepsis or septic shock criteria were enrolled.

Monotherapy received 298 people - the first group, and combination therapy 302 - the second group. The study was conducted from October 16, 2007 to March 23, 2010 in 44 intensive care units in Germany. The number of patients evaluated in the monotherapy group was 273 and 278 in the combination therapy group.

In the first group, patients were prescribed intravenous administration of meropenem 1 g every 8 hours; in the second group, moxifloxacin 400 mg was added to meropenem every 24 hours. The duration of treatment was 7 to 14 days from enrollment in the study to discharge from the intensive care unit or death, whichever occurred first.

The main evaluation criterion was the degree of multiple organ failure according to the SOFA (Sepsis-related Organ Failure) scale, which is a point scale in patients with septic syndrome who are in intensive care. The scale is more intended for quick scoring and description of a number of complications than for predicting the outcome of the disease. State score: from 0 to 24 points, higher values ​​indicate more severe multiple organ failure. Also, the evaluation criterion was all-cause mortality on days 28 and 90. The survivors were followed up for 90 days.

RESULTS: Among the 551 patients evaluated, there was no statistically significant difference in mean SOFA score between groups treated with meropenem and moxifloxacin (8.3 points at 95% CI, 7.8–8.8 points) and meropenem alone (7.9 points; 95% CI 7.5 - 8.4 points) ( R = 0,36).

Also, there was no statistically significant difference in mortality at 28 and 90 days.

By day 28, there were 66 deaths (23.9%, 95% CI 19.0%-29.4%) in the combination group compared with 59 patients (21.9%, 95% CI 17.1%-27 .4%) in the monotherapy group ( P = 0,58).

By day 90, there were 96 deaths (35.3%, 95% CI 29.6%-41.3%) in the combination therapy group compared with 84 (32.1%, 95% CI 26.5%-38, 1%) in the monotherapy group ( P = 0,43).

CONCLUSIONS: In adult patients with severe sepsis, combination treatment with meropenem and moxifloxacin compared with meropenem alone does not reduce the severity of multiple organ failure and does not affect the outcome.

The material was prepared by Ilyich E.A.

💡 And also on the topic:

• Timing and causes of death in septic shock In any pathological condition, there is always a specific cause of death, and in septic shock, people die from multiple organ failure, mesenteric ischemia, or nosocomial pneumonia. But...
• National, regional and global trends in the prevalence of infertility How many infertile couples are there in the world? Not just childless, but those who want to become parents, but are not capable. Almost 48.5 million, somewhere more, somewhere less, but 10 women out of a hundred cannot give birth to a child ...
• Can IVF cause cancer? First Test Tube Baby Louise Brown is now the proud mother of two naturally conceived children. The successes of the last decades in overcoming infertility are enormous. Every year the world...
• 📕 Clinical guidelines Influenza in adults (abbreviated version) Why should the authors of the recommendations remind that “the personal responsibility for the interpretation and use of these recommendations lies with the attending physician”? Isn't it to relieve responsibility from...
• Long-term survival after venous thrombosis Even the smallest, by clinical standards, venous thrombosis does not allow you to breathe freely and relax, since relapse and even death are possible, and the average life expectancy is reduced ...

The statistics of recent years show that the incidence of sepsis and its complications is not decreasing, despite the introduction of modern methods of surgical and conservative treatment and the use of the latest antibacterial agents.

An analysis of the incidence of sepsis in large US centers showed that the incidence of severe sepsis is 3 cases per 1000 population or 2.26 cases per 100 hospitalizations. 51.1% of patients were admitted to the intensive care unit.

The US National Center for Health Statistics published a large retrospective analysis, according to which 10 million cases of sepsis were registered in 500 non-government hospitals during a 22-year follow-up period. Sepsis accounted for 1.3% of all causes of inpatient treatment. The incidence of sepsis increased 3 times from 1979 to 2000 - from 83 to 240 cases per 100,000 population per year.

It should be noted that since the 90s of the last century, there has been a tendency towards an increase in the proportion of gram-negative microorganisms as the most common cause of sepsis.

Previously, it was believed that sepsis is a problem mainly in surgical hospitals. But the spread of nosocomial infections, the use of invasive methods of research and monitoring of the patient's condition, an increase in the number of patients with immunodeficiency states, the widespread use of cytostatics and immunosuppressants, an increase in the number of mixed pathologies have led to an increase in the incidence of sepsis in patients of non-surgical departments.

The existing modern theories of the development of the septic process do not allow revealing the full diversity of the nature and mechanisms of the development of this process. At the same time, they complement our understanding of this complex clinical and pathogenetic process.

The traditional approach to the problem of sepsis from the point of view of infectology is the data presented by V.G. Bochoroshvili. Under sepsis understand nosologically independent infectious disease, characterized by a variety of etiological agents, manifested by bacteremia and a malignant (acyclic) course due to immunosuppression. The acyclic nature of the course of the disease is one of the determining factors, because most of the "classic" infectious diseases (typhoid fever, brucellosis, leptospirosis, typhus and others) occur with bacteremia, but are not sepsis and have a cyclic course with subsequent recovery.

According to A.V. Zinzerling, sepsis is characterized by general and particular characteristic clinical and clinical and anatomical signs, i.e. the presence of bacteremia, septicemia, septicopyemia, entrance gate and generalization of infection.

The interaction of micro- and macroorganism has always been a central aspect in the theory of sepsis. Therefore, sepsis is characterized by a diverse range of microbiological factors, which in most cases are representatives of the facultative flora of open cavities of the human body. At the same time, bacteremia in sepsis does not differ from that in "classic" infectious diseases. It has not been established that causative agents of sepsis have special virulent properties. Mostly they are representatives of the facultative flora of the human body, therefore they do not have a pronounced immunogenicity. This explains the acyclicity and fatality of the clinical course of sepsis.

Since 1992, sepsis has been considered in close connection with the systemic inflammatory response syndrome (SIRS) - a nonspecific reaction of the immune system to an infectious agent or damage (Bone R.C., 1992). Thus, SIRS is a pathological condition caused by one of the forms of surgical infection and/or tissue damage of a non-infectious nature (trauma, pancreatitis, burns, ischemia or autoimmune tissue damage, etc.). This concept was proposed by the American College of Pulmonologists and the Society of Critical Medicine Specialists (ACCP / SCCM), which led to a significant revision of the concept of pathogenesis, clinic, treatment and prevention of sepsis and its complications. SIRS is characterized by the presence of more than one of the following four main clinical features characteristic of inflammation: hyperthermia, tachycardia, tachypnea, hemogram changes (leukocytosis/leukopenia) .

The above clinical signs can occur with sepsis, but the presence of an infectious focus in tissues or organs is mandatory.

Thus, the current classification of sepsis is based on the diagnostic criteria proposed at the ACCP/SCCM consensus conference.

Local inflammation, sepsis, severe sepsis and multiple organ failure are links in the same chain in the body's response to inflammation and, as a result, generalization of microbial infection. Severe sepsis and septic shock constitute an essential part of the syndrome of the systemic inflammatory response of the body to an infectious agent, and the result of the progression of systemic inflammation is the development of dysfunction of systems and organs.

The modern concept of sepsis based on SIRS is not absolute and is criticized by many domestic and Western scientists. The ongoing controversy regarding the clinical definition of SIRS and its relationship to the infectious process and specificity for sepsis still raises the issue of bacteriological diagnosis, which in many cases is a decisive factor in confirming the infectious nature of the pathological process.

Bacteremia is one of the important, but not mandatory, manifestations of sepsis, since periodicity in its manifestation is possible, especially in cases of a long course of the disease. The absence of confirmed bacteremia should not affect the diagnosis in the presence of the above clinical criteria for sepsis, which is important for the attending physician when deciding on the amount of therapy. Even with the most scrupulous observance of the technique of blood sampling and the use of modern microbiological technologies for diagnosis in patients with the most severe course of sepsis, the frequency of positive results, as a rule, does not exceed 40-45%.

Detection of microorganisms in the bloodstream without clinical and laboratory confirmation of SIRS should be regarded as transient bacteremia, which can occur with salmonellosis, yersiniosis, and a number of other intestinal infections. High and prolonged bacteremia, signs of generalization of the infectious process are of significant clinical importance in the diagnosis of sepsis.

Detection of the pathogen is an important argument in favor of the diagnosis of sepsis due to:

- evidence of a mechanism for the development of sepsis (for example, catheter-associated infection, urosepsis, gynecological sepsis);

- confirmation of the diagnosis and determination of the etiology of the infectious process;

- rationale for choosing an antibiotic therapy regimen;

- evaluation of the effectiveness of therapy.

A positive result of blood culture for sterility is the most diagnostically informative method of research. Blood cultures should be carried out at least 2 times a day (within 3-5 days), as soon as possible after the start of the temperature rise or 1 hour before the introduction of antibiotics. To increase the probability of isolation of the pathogen, 2-4 inoculations can be made sequentially with an interval of 20 minutes. Antibacterial therapy sharply reduces the possibility of isolating the pathogen, but does not exclude a positive result of blood culture for sterility.

The role of the polymerase chain reaction in the diagnosis of bacteremia and the interpretation of the obtained results remains unclear for practical application.

Negative blood culture results do not rule out sepsis. In such cases, it is necessary to take material for microbiological examination from the alleged source of infection (cerebrospinal fluid, urine, sputum culture, discharge from the wound, etc.). When searching for a focus of infection, it is necessary to remember the possible translocation of opportunistic microflora from the intestine against the background of a decrease in local resistance in the intestinal wall - circulatory disorders, chronic inflammation in combination with general immunosuppression.

When making a diagnosis of "sepsis", it is necessary to take into account the following signs indicating the generalization of the infection:

- detection of leukocytes in body fluids that are normally sterile (pleural, cerebrospinal fluid, etc.);

- perforation of a hollow organ;

- radiographic signs of pneumonia, the presence of purulent sputum;

- clinical syndromes in which there is a high probability of an infectious process;

- fever with the manifestation of severe intoxication, possibly of a bacterial nature;

- hepatosplenomegaly;

- the presence of regional lymphadenitis at the site of possible entry gates of infection;

- polyorganism of the lesion (pneumonia, meningitis, pyelonephritis);

- skin rashes (polymorphic rash, frequent combination of inflammatory and hemorrhagic elements);

- signs of DIC, etc.

Sepsis therapy It is aimed at eliminating the focus of infection, maintaining hemodynamics and respiration, correcting homeostasis disorders. The treatment of sepsis is a complex task that requires a multidisciplinary approach, which includes surgical debridement of the focus of infection, the appointment of an adequate etiology of antibacterial treatment, and the use of methods of intensive care and prevention of complications.

Given the fact that the onset of sepsis development is associated with the reproduction and circulation of microorganisms, and etiological confirmation requires a certain time, the attending physician faces the question of choosing an adequate antibacterial drug (ABD) for empirical therapy and criteria for evaluating the effectiveness of therapy.

According to retrospective studies, early administration of effective antibiotic therapy correlated with a decrease in mortality in the treatment of uncomplicated sepsis. Therefore, an important point in the choice of antibiotics for empirical therapy of sepsis is:

- the alleged etiology of the process;

- the spectrum of action of the drug;

- method and characteristics of dosing;

— security profile.

It is possible to suggest the nature of the microflora that caused SIRS based on the localization of the primary focus of infection (Table 2).

Thus, even before obtaining the results of bacteriological culture, focusing on the alleged focus of the bacterial infection, one can choose an effective scheme of empirical antibiotic therapy. It is recommended to carry out microbiological monitoring of the seeded microflora in each clinic, which makes it possible to draw up a “microbiological passport of the hospital”. This must be taken into account when prescribing ABP.

Local epidemiological data on the structure of pathogens and their sensitivity to ABP should be taken into account, which can be the basis for creating local protocols for empirical antibiotic therapy.

In empiric therapy of sepsis, a combination of two antibiotics is most often used. Arguments in favor of prescribing combination therapy are:

- the inability to differentiate the gram-positive or gram-negative etiology of infection according to the clinical picture;

- high probability of polymicrobial etiology of sepsis;

- the risk of developing resistance to one of the antibiotics.

With continued clinical efficacy, antibiotic therapy continues to be carried out with starting drugs prescribed empirically. In the absence of a clinical effect within 48-72 hours, antibiotics should be replaced taking into account the results of a microbiological study or, if there are none, with drugs that bridge the gaps in the activity of starting antibiotics, taking into account the possible resistance of pathogens.

In sepsis, ABP should be administered only intravenously, selecting the maximum doses and dosing regimens according to the level of creatinine clearance. A limitation to the use of drugs for oral and intramuscular administration is a possible violation of absorption in the gastrointestinal tract and a violation of microcirculation and lymph flow in the muscles. The duration of antibiotic therapy is determined individually.

ABP therapy faces the following challenges:

- to achieve sustainable regression of inflammatory changes in the primary infectious focus;

- to prove the disappearance of bacteremia and the absence of new infectious foci;

- stop the reaction of systemic inflammation.

But even with a very rapid improvement in well-being and obtaining the necessary positive clinical and laboratory dynamics (at least 3-5 days of normal temperature), the standard duration of therapy should be at least 10-14 days, taking into account the recovery of laboratory parameters. Longer antibiotic therapy is required for staphylococcal sepsis with bacteremia (especially caused by MRSA strains) and localization of the septic focus in the bones, endocardium and lungs.

The use of III generation cephalosporins combined with beta-lactamase inhibitors is reasonable in the treatment of sepsis.

Highly effective is the combination of cefoperazone and sulbactam - Cefosulbin. Cefoperazone is active against aerobic and anaerobic Gram-positive and Gram-negative microorganisms (Table 3). Sulbactam is an irreversible inhibitor of beta-lactamases, which are secreted by microorganisms resistant to beta-lactam antibiotics. It prevents the destruction of penicillins and cephalosporins by beta-lactamases. In addition, sulbactam binds to penicillin-binding proteins, shows synergism when used simultaneously with penicillins and cephalosporins.

Thus, the combination of sulbactam and cefoperazone makes it possible to achieve a synergistic antimicrobial effect against microorganisms sensitive to cefoperazone, which reduces the minimum inhibitory concentration by 4 times for these bacteria and increases the effectiveness of therapy.

The data of a number of studies show that 80-90% of strains of microorganisms isolated from patients with sepsis are sensitive to cefoperazone / sulbactam (Cefosulbin), including strains A. baumannii and P. aeruginosa. The use of cefoperazone / sulbactam (Cefosulbin) is not inferior to carbapenems in terms of clinical efficacy and can be an alternative to the frequently used combination of III generation cephalosporins and aminoglycosides.

High clinical and microbiological efficacy has been shown in the treatment of sepsis (up to 95%) caused by multidrug-resistant strains of gram-negative and gram-positive microorganisms.

Thus, the range of antibacterial activity of cefoperazone / sulbactam (Cefosulbin) against anaerobic pathogens allows us to recommend this drug in the treatment of abdominal, surgical and gynecological sepsis.

Clinical efficacy in the treatment of infectious complications using cefoperazone / sulbactam (Cefosulbin) is shown in a group of patients with burns and oncological pathology.

Early appointment of effective etiotropic therapy is an important factor in the treatment of sepsis and often decides the fate of the patient. In many cases, the attending physician does not have a reserve of time for the selection of antibiotics, which is due to the severity of the clinical course of sepsis, so the most effective antibacterial agent with the widest possible spectrum of antibacterial action is needed. Given the wide spectrum of antimicrobial activity, the possibility of intravenous use, good pharmacokinetics and pharmacodynamics of cefoperazone / sulbactam (Cefosulbin), this combined antibacterial drug can be recommended as the first line of empirical therapy for the treatment of sepsis.

Thus, taking into account the high clinical efficacy shown in a number of clinical studies, good pharmacological safety, cefoperazone / sulbactam (Cefosulbin) may be the drug of choice in the treatment of sepsis until bacteriological confirmation is obtained.

Table 11

End of work -

This topic belongs to:

Selected Lectures on Internal Medicine

On the site site read: "selected lectures on internal diseases"

If you need additional material on this topic, or you did not find what you were looking for, we recommend using the search in our database of works:

What will we do with the received material:

If this material turned out to be useful for you, you can save it to your page on social networks:

All topics in this section:

Stages of diagnostic search for LNG
Stage 1 ¾ additional clinical and laboratory symptoms are detected based on routine examination methods (OAC, OAM, BAC, chest x-ray, ECG) and carefully collected

LNG (+) musculoskeletal syndrome
Disease Clinical and laboratory symptoms Examination methods

LNG (+) skin lesions
Drug allergic reaction Drug rashes: urticaria, mucosal ulceration, angioedema, arthralgias, eosinophilia, association with drug intake and disappearance of l

LNG (+) enlargement of the spleen
Sepsis (IE) Mild, enlarged spleen, shaking chills, severe sweating and intoxication, hemorrhagic syndrome, anemia, changes in urine, may be present

Diagnostic search in patients with isolated LNG
Causes of this LNG: sepsis, TVS, lymphogranulomatosis, IE, hypernephroma, DLST (SLE), cholangitis, leukemia, drug disease and artificial L. So, if a patient has a combination of LNG and repeated oz

Heart arrhythmias
Cardiac arrhythmias ¾ is a change in the normal heart rate, regularity and source of action of the heart, as well as a violation of the connection or sequence between the activation of the atria and the stomach

quick rhythm
Sinus tachycardia (ST) with a heart rate of more than 100 per minute (rarely more than 140 per minute). ST ¾ is not a rhythm disorder, but a normal physiological response to an increase in sympathetic tone.

Arrhythmias as a disease syndrome
Pathology OI

Efficacy of various antiarrhythmics in arrhythmias
ST drug Supraventricular ES Ventricular ES SPT PVT Paroxysm MA Ia, novocaine

Clearly wrong rhythm
Extrasystole (ES) ¾ is the most common rhythm disorder that a doctor has to deal with. This is a premature (early) contraction of some department or the whole heart

Cordarone, rhythmilene, aymaline, ethacizine are effective in both atrial and ventricular ES.
With ES and a tendency to tachycardia (heart rate over 100), it is better to administer: b-AB, cordarone or isoptin (2-4 ml of a 0.25% solution, that is, 5-10 mg); In ES with bradycardia, rit is preferred

Etiology of MA
Organic heart diseases dominate (in 80% of cases) with the presence of hypoxia, hypercapnia, metabolic and hemodynamic disorders: rheumatic mitral heart disease and coronary artery disease with

TP relief algorithm
Symptoms of acute cardiovascular failure (systolic blood pressure less than 90 mm Hg, CA, OL, syncope or angina attacks) ß ß no yes ß &szli

Bowel disease
Diseases of the intestines (thin and large) develop in humans much more often than they are detected clinically. Chronic bowel diseases have always been and remain difficult to diagnose and

Hvzk treatment
Therapy of CIBD, especially severe forms, often presents significant difficulties, primarily due to the lack of etiotropic therapy (the etiology of CIBD is unknown). Treatment for BCR is based on

Glomerulonephritis
In detail, the clinic of glomerulonephritis (synonym: nephritis), as an inflammatory lesion of the glomeruli, was described in 1827 by the English physician Bright. Glomerulonephritis (GN) ¾ is non-specific

The pathogenesis of opgn
An important feature of APGN ¾ is the presence of a latent period between the manifestations of infection and the subsequent appearance of symptoms of nephritis. So, when the pharynx is infected, the latent period is 7-10

Clinic OPGN
The number of cases of asymptomatic course of APGN is 3-4 times higher than the number of cases of APGN with obvious clinical symptoms. APGN may occur as endemic outbreaks or as sporadic cases.

CGN clinic
CGN is characterized by a variety of symptoms and occurs with periods of exacerbations and remissions. Often, CGN is detected only by chance detection of abnormalities in urinalysis or hypertension during various examinations.

Non-pharmacological therapy for CGN
Compliance with strict bed rest (within 2-4 weeks, sometimes up to 2-3 months), especially with hypertensive or mixed forms of CGN. FN may exacerbate renal ischemia, hematuria, and proteinuria.

Chronic pyelonephritis and chronic renal failure
Chronic pyelonephritis (chronic tubulo-interstitial bacterial nephritis) ¾ is a non-specific infectious and inflammatory process in the mucous membrane of the urinary tract (pelvis,

HP Clinic
A latent course (with a minimum number of symptoms) occurs in every fifth patient with CP. Most of these patients have no subjective symptoms: no complaints (and if

Prognosis and outcomes of CP
CP accompanies a person all his life: it usually begins in childhood, later there are relapses of exacerbations, which eventually leads to chronic renal failure. In the elderly, the prognosis of CP is always serious due to atypical

The use of AB depending on the type of microbe
First-line AB microbe Reserve funds E. coli Ampicillin, amoxiclav, unazine, cephalosporins of the 1st-2nd generation

Treatment of chronic renal failure
Secondary prevention of CRF is important, achieved by a rational diet, adequate treatment of kidney disease with correction of hypertension, kidney and urinary tract infections, their obstruction (MKD, BPH). Treatment of chronic renal failure

List of abbreviations
AB ¾ antibiotics A-B ¾ atrioventricular hypertension ¾ arterial hypertension

Inadequate initial antibiotic therapy, defined as the lack of in vitro effect of an antimicrobial agent against an isolated pathogen responsible for the development of an infectious disease, is associated with increased morbidity and mortality in patients with neutropenic fever or severe sepsis. To reduce the likelihood of inappropriate antibiotic therapy, recent international guidelines for the treatment of sepsis have proposed empiric therapy targeting Gram-negative bacteria, especially when Pseudomonas infection is suspected. However, the authors of this recommendation are aware that "there is no single study or meta-analysis that has convincingly demonstrated superior clinical outcome of combination therapy in a specific patient population for specific pathogens."

Theoretical basis for prescribing combination therapy:

• an increase in the likelihood that at least one drug will be active against the pathogen;
• prevention of persistent superinfection;
• immunomodulatory non-antibacterial effect of the secondary agent;
• enhancement of antimicrobial action based on synergistic activity.

Unlike patients with febrile neutropenia, which has been repeatedly and well studied, there have been no randomized trials of severe septic patients with increased capillary permeability syndrome and multiple organ failure, in which the distribution and metabolism of antibiotics may be impaired.

The essence of the study of empiric treatment of sepsis

The main aim of this study was to compare the effectiveness of combination therapy with two broad-spectrum antibiotics moxifloxacin and meropenem with meropenem monotherapy in multiple organ failure caused by sepsis.

METHODS: A randomized, open, parallel group study was conducted. 600 patients with severe sepsis or septic shock criteria were enrolled.

Monotherapy received 298 people - the first group, and combination therapy 302 - the second group. The study was conducted from October 16, 2007 to March 23, 2010 in 44 intensive care units in Germany. The number of patients evaluated in the monotherapy group was 273 and 278 in the combination therapy group.

In the first group, patients were prescribed intravenous administration of meropenem 1 g every 8 hours; in the second group, moxifloxacin 400 mg was added to meropenem every 24 hours. The duration of treatment was 7–14 days from enrollment in the study to discharge from the intensive care unit or death, whichever occurred first.

The main evaluation criterion was the degree of multiple organ failure according to the SOFA scale, which is a point scale in patients with septic syndrome. State score: from 0 to 24 points, higher values ​​indicate more severe multiple organ failure. Also, the evaluation criterion was all-cause mortality on days 28 and 90. The survivors were followed up for 90 days.

RESULTS: Among the 551 patients evaluated, there was no statistically significant difference in mean SOFA score between groups treated with meropenem and moxifloxacin (8.3 points at 95% CI, 7.8-8.8 points) and meropenem alone (7.9 points - 95% CI 7 .5-8.4 points) (P = 0.36).

Also, there was no statistically significant difference in mortality at 28 and 90 days.

By day 28, there were 66 deaths (23.9%, 95% CI 19.0%-29.4%) in the combination group compared with 59 patients (21.9%, 95% CI 17.1%-27 .4%) in the monotherapy group (P = 0.58).

By day 90, there were 96 deaths (35.3%, 95% CI 29.6%-41.3%) in the combination therapy group compared with 84 (32.1%, 95% CI 26.5%-38, 1%) in the monotherapy group (P = 0.43).

CONCLUSIONS: In adult patients with severe sepsis, combination treatment with meropenem and moxifloxacin compared with meropenem alone does not reduce the severity of multiple organ failure and does not affect the outcome.

Video: