Qiu Haibo Xu Jingyuan Intensive Care Medicine

Severe infection and septic shock are clinical syndromes resulting from systemic infection, characterized by organ dysfunction. ,  The case fatality rate is as high as 30 % ~ 70%, is ICU The primary cause of mortality among critically ill patients. In recent years, the widespread use of broad-spectrum antibiotics has… ,  Induce multidrug resistance (Laughing) Severe infections caused by Gram-negative bacteria have increased significantly. ,  It has become the leading cause of death among critically ill patients. To this end, ,  Exploring standardized and effective treatment approaches ,  It is indeed an urgent priority.

1 MDR The situation regarding severe infections caused by Gram-negative bacteria is grave.

MDR Gram-negative bacteria have become ICU Severe infections are becoming an increasingly serious problem. ,  It is also a common pathogen responsible for hospital-acquired pneumonia, intra-abdominal infections, and urinary tract infections. Epidemiological studies have shown that… ,ICU In severe infections, infections caused by Gram-negative bacteria account for as much as 70 % . It is generally believed that bacteria of the family Enterobacteriaceae are ICU The most common pathogens causing hospital-acquired infections ,  However, the survey shows MDR The detection rate of Gram-negative bacteria has increased significantly. ,  It mainly includes Pseudomonas aeruginosa and Acinetobacter species. (  Acinetobacter baumannii )  , production of extended-spectrum β-lactamases -  Lactamase (ESBL) and carbapenem-resistant Enterobacteriaceae, among others.

MDR Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacter species occupy a critically important position in hospital-acquired pneumonia. According to the U.S. National Nosocomial Infection Surveillance System, ( NNIS) information of ,  In 1986 Year to 2003  year ICU In hospital-acquired infections ,  The proportion of Acinetobacter has increased significantly. ,  Moreover, drug resistance has also increased significantly. Recently… ,  Investigations into ventilator-associated pneumonia have shown that ,  Carbapenem resistance rate of Pseudomonas aeruginosa 26.4%, Moreover, the resistance rate of Acinetobacter baumannii to carbapenems is even higher. 36.8% . Greek surveys indicate ICU The resistance rate of Acinetobacter baumannii to carbapenems is as high as 85 % . Even more serious is ,  In recent years, polymyxin-resistant Acinetobacter species have emerged. MDR Gram-negative bacteria pose significant challenges in the treatment of critically ill patients. ,  Prolonged hospital stay and increased medical expenses ,  Mortality has increased significantly. Some studies have examined… MDR Attributable mortality rate of Gram-negative bacteria ( attributable mortality) Conduct analysis ,  Display MDR Caused by Acinetobacter baumannii ICU The case-fatality rate among critically ill patients has increased. 10% ~ 43 % . Therefore ,MRD The situation regarding severe infections caused by Gram-negative bacteria is extremely grave. ,  It should attract widespread attention and due consideration.

2 MDR Therapeutic Challenges in Severe Infections Caused by Gram-Negative Bacteria

In view of MDR High morbidity and mortality rates associated with severe infections caused by Gram-negative bacteria ,  Early, effective antimicrobial therapy is of particular importance. ;  However ,  Early effective treatment depends on the understanding of MDR Accurate identification of Gram-negative bacteria. In fact, ,  As early as 2005 year ,  American Thoracic Society ( ATS) and the Infectious Diseases Society of America (IDSA)HAP The guideline proposes ,  For the existence of MDR Patients with relevant high-risk factors ,  Empirical broad-spectrum antibiotic therapy is required. ,  To ensure the efficacy of anti-infective therapy. ,  And based on the epidemiological investigation, a judgment was made. MDR Basis for identifying the pathogen. The main criteria include :( 1) Previously 90 d Has received antibacterial therapy previously. ;( 2) Hospitalization exceeding 5 d ;( 3) High rates of bacterial resistance are prevalent in community settings or specialized hospital wards. ;( 4) Healthcare-associated pneumonia exists. (HCAP) Risk factors of ;( 5) There are immunosuppressive diseases and (  or )  Undergoing treatment with immunosuppressants. Based on these findings, it may be possible to achieve… MDR Early diagnosis and treatment of bacterial infections. In accordance with ATS The guideline is used to determine whether critically ill patients have… MDR Risk factors for bacteria ,  Guidance on the early selection of broad-spectrum antibacterial agents ,  It can reduce the duration of mechanical ventilation in patients with severe infections and ICU Shortened hospital stay ,  And it can improve the prognosis.

Under normal circumstances ,ICU All critically ill patients possess MDR Risk factors for bacterial infection ,  But not all ICU Infections in critically ill patients are all MDR Caused by bacteria ,  The overuse of broad-spectrum antibiotics ,  This will inevitably lead to a further increase in bacterial resistance rates.

A recent study on ATS The guide is for MDR A prospective observational study on the accuracy of bacterial prediction showed that ,  Application ATS Standard Forecast MDR The negative predictive value of the infection is as high as 96%, And the positive predictive value is only 18 % . No prompt MDR Most patients with risk factors are absent. MDR Bacterial infection ,  No need to administer broad-spectrum antibacterial therapy. ;  And existence MDR Only a small proportion of patients with risk factors are MDR Bacterial infection ,  It requires treatment with broad-spectrum antibacterial agents. In other words, ,  Most patients who do not require treatment with broad-spectrum antibacterial agents. ,  However, the patient received treatment with broad-spectrum antibacterial agents. ,  It will inevitably lead to an increase in bacterial resistance. ,  to make MDR The crisis of untreatable bacterial infections is drawing ever closer.

3 MDR Strategies for Managing Severe Gram-Negative Bacterial Infections

Accurate assessment and prevention and control MDR Severe bacterial infections are of great significance. In ATS/ IDSA On the basis of the guidelines ,  First, assess whether the critically ill patient has… MDR At the same time as risk factors ,  Should be actively carried out MDR Bacterial monitoring and screening ,  Understand MDR Predicted positive predictive value ;  Secondly ,  It is necessary to carefully differentiate between bacterial infection and colonization. ;  Finally , While implementing early empirical therapy, ,  Efficacy assessment and microbiological testing are required. ,  Initiate targeted therapy as early as possible. ,  Implement step-down therapy , Thus, it helps avoid the overuse of broad-spectrum antimicrobial agents resulting from the indiscriminate implementation of guidelines.

3 .1  Active bacterial screening ,  Clear MDR Epidemiological status of bacteria

For ICU Patients with severe infections ,  Whether or not it exists MDR High-risk factors ,  All require early bacterial screening. ,  To guide subsequent prevention and control measures. ICU Patients often present with MDR Risk factors for bacterial infection ,  For MDR High-risk groups for infection. Nseir Pending report ,  New entry detection ICU The patient’s nasal vestibule, rectal swab, and airway secretions ,  There is 64 % The patient has MDR Risk factors ,  But only 13 % Patient admission ICU Screened at the time MDR . The Zhongda Hospital, Affiliated to Southeast University ICU Bacterial screening of the patients’ nasal vestibules was also performed. ,  It was found through the mid-term review that… ,MDR The detection rate is significantly higher than that reported in foreign studies. ,  Gundam 60 % . Therefore ,  Early bacterial screening can help establish the current local bacterial epidemiology. ,  Thereby guiding subsequent prevention and control efforts.

3 .2  Strive to differentiate between infection and colonization.

For those identified through early screening MDR Patient with bacteria ,  Differentiating between infection and colonization is very difficult. Most… ICU The patient has MDR Risk factors for infection ,  Such as recent hospitalization, antibiotic therapy, or long-term residence in a nursing facility, etc. ,  At this point, microbiological findings are combined with infection-related biomarkers. ,  It may help differentiate between infection and colonization.

Collect lower respiratory tract secretions and perform quantitative culture. ,  It helps to establish a definitive diagnosis of severe pneumonia. ,  And exclude colonization. Cases with bacterial quantitative cultures exceeding the threshold may be considered to represent infection. ,  If below the threshold, it is classified as colonization or contamination. Protective pulmonary brush. ( PSB) Quantitative culture of secretions for bacterial colony count > 10³  cfu/mL Diagnostic criteria for pulmonary infection ,  Bronchoalveolar lavage (BAL) Quantitative culture of secretions must be greater than 10⁴  cfu/mL, And direct tracheal aspiration (tracheal aspirates, TA) Secretion culture with >10⁶  cfu/mL For diagnostic criteria. Of course. ,  Quantitative culture techniques are complex. ,  Time-consuming ,  This has limited its clinical application. Smear examination of lower respiratory tract secretions also helps differentiate colonization from infection. ,  Moreover, it is easy to operate. It is generally believed that ,  For qualified lower respiratory tract specimens ,  If it is found that the white blood cells engulfing bacteria have reached 2 % ~ 5%, This indicates the presence of a bacterial infection.

On the basis of microbiological diagnosis ,  Combined monitoring of infection-related biomarkers helps to differentiate between infection and colonization. Procalcitonin (PCT) It is an intermediate product in the production of inflammatory cytokines during systemic infection. ,  When the plasma mass concentration reaches 0 .25  ~ 0.5 mg/L It can serve as the standard for initiating antimicrobial therapy. ,  And during the treatment process ,  If PCT Reduce ,  Below that level ,  Then discontinuation of the antibiotic may be considered. In addition, ,  Bronchoalveolar lavage may be applied. (BAL) Soluble triggering receptor I expressed by myeloid cells in the fluid ( sTREM- I )  Diagnosis of bacterial ventilator-associated pneumonia (VAP), Some reports suggest that this is superior to the clinical pulmonary infection score and… PCT More accurate. When BAL In liquid sTREM-I Mass concentration greater than 200 pg/mL Time ,  Its diagnosis VAP The sensitivity is 74%, Specificity 88 % 。

3 .3  Early empirical therapy

For patients diagnosed with severe infections , Early treatment with broad-spectrum antimicrobial agents can significantly reduce mortality. Empirical therapy involves selecting antimicrobial agents based on the patient’s source of infection, the site of infection, prior antimicrobial treatment history, and the local epidemiology of bacterial pathogens. In cases where severe infection or septic shock has been confirmed… ICU Patient ,  Specimens should be collected immediately. ,  and also 1 hour Administer antibacterial therapy internally. ,  Moreover, antimicrobial agents should, whenever possible, cover the likely causative pathogens. If the initial empirical antimicrobial regimen is inappropriate, ,  Cannot suppress pathogenic bacteria. ,  Consequently, the case-fatality rate of severe infections will increase significantly.

3 .4  Initiate targeted antimicrobial therapy as soon as possible.

Use of antibacterial agents 2  ~ 3 d after ,  Efficacy should be assessed based on microbiological culture results and clinical response. ,  Initiate targeted antimicrobial therapy as soon as possible. Culture and susceptibility testing are the foundation for the rational use of antimicrobial agents. ,  Moreover, the accurate, timely, and repeated submission of specimens is essential for obtaining reliable bacterial culture and antimicrobial susceptibility results. ICU The patient’s condition is critical. ,  In the early stages of severe infections, microbiological culture results are often negative or reveal multidrug-resistant bacteria. ,  It is extremely challenging to select sensitive and effective antimicrobial agents based on susceptibility test results.

3.5 MDR Selection of Therapeutic Agents for Gram-Negative Bacterial Infections

In recent years ,MDR Pneumonia caused by Acinetobacter is increasing year by year. , Moreover, strains resistant to carbapenems and even polymyxins have emerged. ,  Treatment is extremely challenging. Commonly used antibiotics for Acinetobacter include carbapenems, aminoglycosides, and polymyxins. Acinetobacter exhibits variable susceptibility to carbapenem antibiotics. ,  Fluctuating between 32 % ~ 90%, Moreover, imipenem and meropenem do not exhibit equivalent susceptibility against Acinetobacter. , It should be based on the antibiotic susceptibility results. ,  Determines the choice of antibiotic. Inhalation tobramycin as… FDA The only approved aminoglycoside for the treatment of pulmonary fibrosis infections. ,  It also shows a certain efficacy in treating Acinetobacter. Polymyxin therapy. MDR The susceptibility of Acinetobacter is in 55 % The above. Additionally, other studies have shown ,  Apply ampicillin /  Treatment with sulbactam or in combination with carbapenems MDR Acinetobacter ,  May improve patient prognosis. ,  Reduce the case-fatality rate ,  However, the optimal dosage of sulbactam remains unclear at present.

In short, ,MDR Gram-negative bacteria have become ICU The main pathogenic bacteria causing severe infections ,  It is also the primary pathogen responsible for mortality in patients with severe infections. In the face of the current situation… MDR Challenges in the Diagnosis and Treatment of Gram-Negative Bacterial Infections ,  Positive MDR Risk factor assessment and MDR Bacterial screening ,  Strive to differentiate between bacterial infection and colonization. ,  Implement early empirical therapy, guided by clinical response and microbiological testing. ,  Initiate targeted therapy as early as possible. ,  Implement step-down therapy ,  Only then is it possible to improve the prognosis of patients with severe infections and avoid… MDR Bacterial resistance rates are steadily increasing.